umu.sePublications
Change search
Refine search result
1 - 34 of 34
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the 'Create feeds' function.
  • 1.
    Asikainen, Sirkka
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, Oral Microbiology.
    Doğan, Başak
    Department of Periodontology, Faculty of Dentistry, Marmara University, Istanbul, Turkey.
    Turgut, Zeynep
    Department of Periodontology, Gazi University, Ankara, Turkey.
    Paster, Bruce J
    Department of Molecular Genetics, The Forsyth Institute, Boston, Massachusetts, United States of America.
    Bodur, Aysen
    Department of Periodontology, Gazi University, Ankara, Turkey.
    Oscarsson, Jan
    Umeå University, Faculty of Medicine, Department of Odontology, Oral Microbiology.
    Specified species in gingival crevicular fluid predict bacterial diversity2010In: PloS one, ISSN 1932-6203, Vol. 5, no 10, e13589- p.Article in journal (Refereed)
    Abstract [en]

    Among a variety of detected species those traditionally classified as Gram-negative anaerobes growing in mature subgingival biofilms were the main predictors for species diversity in GCF samples as well as responsible for distinguishing GCF samples from PP samples. GCF bacteria may provide new prospects for studying dynamic properties of subgingival biofilms.

  • 2.
    Asikainen, Sirkka E
    Umeå University, Faculty of Medicine, Odontology, Oral Microbiology.
    Periodontal bacteria and cardiovascular problems.2009In: Future microbiology, ISSN 1746-0921, Vol. 4, 495-498 p.Article in journal (Other academic)
  • 3.
    Asikainen, Sirkka
    et al.
    Umeå University, Faculty of Medicine, Odontology.
    Karched, Maribasappa
    Umeå University, Faculty of Medicine, Odontology.
    Molecular techniques in oral microbial taxonomy, identification and typing2008In: Molecular Oral Microbiology, Caister Academic Press, Norfolk UK , 2008, 1-27 p.Chapter in book (Refereed)
    Abstract [en]

    The rapid development of molecular techniques during the past decade has revolutionized the field of microbiology. Two issues are of profound importance. First, the discovery of phylogenetically informative DNA sequences, such as the 16S rRNA gene, radically changed the concept of bacterial relatedness and provided a universal system for bacterial identification and categorization. Second, it became possible to detect, identify, and type bacteria independent of their cultivability and, by these new means, to elucidate the diversity and spatial organization of complex oral bacterial communities. Of considerable benefit has been the fact that the same nucleic acid-based molecular approaches can be applied in all microbial environments, ranging from the oral cavity, to the surfaces of historical monuments, to the depths of open oceans. This has led to development of versatile PCR- and hybridization-based techniques that allow a rapid and convenient analysis of the bacterial contents of oral samples and offer previously unattainable possibilities for expanding studies on bacterial epidemiology and characterization. In particular, the emerging new microarray technology will facilitate great strides in understanding the structure and dynamics of oral bacterial communities and bacteria-host interactions, and will form the basis for developing novel diagnostics for oral infections.

  • 4. Dogan, B
    et al.
    Antinheimo, J
    Cetiner, D
    Bodur, A
    Emingil, G
    Buduneli, E
    Uygur, C
    Firatli, E
    Lakio, L
    Asikainen, Sirkka
    Umeå University, Faculty of Medicine, Odontology, Oral Microbiology.
    Subgingival microflora in Turkish patients with periodontitis.2003In: Journal of Periodontology, ISSN 0022-3492, E-ISSN 1943-3670, Vol. 74, no 6, 803-814 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: No information exists on periodontitis-associated subgingival microbiota from Turkey. We determined the occurrence, interspecies relationships, and clonal characteristics for a group of periodontal bacteria in a Turkish study population. METHODS: Subgingival microbial samples were obtained from patients with localized (LAgP, N = 18) or generalized (GAgP, N = 17) types of aggressive periodontitis, generalized chronic periodontitis (GCP, N = 14), and non-periodontitis subjects (N = 20). Culture methods were used to recover 6 periodontal bacterial species and yeasts, and a polymerase chain reaction technique was used to detect Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis. Intraspecies characterization of A. actinomycetemcomitans was carried out by serotyping and genotyping. RESULTS: All species, except for Micromonas micros (formerly Peptostreptococcus micros) occurred more frequently (P < 0.05) in periodontitis than non-periodontitis subjects. Detection frequencies for Tannerella forsythensis (formerly Bacteroides forsythus) and Campylobacter rectus differed among the periodontitis subgroups; the lowest frequency occurred in LAgP. The mean proportions of A. actinomycetemcomitans, P. gingivalis, and C. rectus were higher (P < 0.008) in GAgP than in non-periodontitis subjects. Significant positive associations were seen between 7 of the 22 possible combinations (P < 0.05). A. actinomycetemcomitans serotype c (34%) and non-serotypeable isolates (34%) were the most common antigenic types among the 305 strains analyzed. Eleven arbitrarily primed (AP)-PCR genotypes were distinguished among 273 isolates from 29 subjects. Yeasts were found in 23% of the 69 subjects. CONCLUSIONS: The results on the Turkish study population were generally in line with earlier reports on the occurrence and interspecies relationships of certain bacteria in periodontitis. However, A. actinomycetemcomitans was not overrepresented in LAgP, and the serotype distribution resembled that reported from the East. The high frequency of non-serotypeable isolates suggests local characteristics of the species.

  • 5. Dogan, B
    et al.
    Buduneli, E
    Emingil, G
    Atilla, G
    Akilli, A
    Antinheimo, J
    Lakio, L
    Asikainen, Sirkka
    Umeå University, Faculty of Medicine, Odontology, Oral Microbiology.
    Characteristics of periodontal microflora in acute myocardial infarction.2005In: Journal of Periodontology, ISSN 0022-3492, E-ISSN 1943-3670, Vol. 76, no 5, 740-748 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Periodontitis has been linked to increased risk of cardiovascular diseases. Systemic reactions associated with cardiovascular events may depend on characteristics of the subgingival microflora in periodontitis. Our objectives were to compare the numbers of cultivable bacteria, composition of subgingival microflora and clonal distribution of Actinobacillus actinomycetemcomitans (A. actinomycetemcomitans) in two groups of patients with generalized chronic periodontitis (GCP), one with an acute myocardial infarction (AMI-GCP) and the other one without AMI (non-AMI-GCP). METHODS: In all, 150 dentate individuals were screened for suitability to this study. Subgingival bacterial samples were collected from 11 AMI-GCP and 11 non-AMI-GCP patients who had been selected using strict inclusion criteria in an attempt to exclude confounding factors and to increase comparability of periodontal conditions by matching for periodontal probing depths and attachment levels. Culture methods were used to determine the total viable counts and occurrence and proportions of six periodontal bacterial species and yeasts. Polymerase chain reaction (PCR) technique was used to detect A. actinomycetemcomitans and Porphyromonas gingivalis (P. gingivalis). Intraspecies characterization of A. actinomycetemcomitans included serotyping and genotyping. RESULTS: The mean proportions of P. gingivalis (P = 0.05) and Tannerella forsythensis (T. forsythensis) (P = 0.01) were significantly lower, but the numbers of Micromonas micros (M. micros) and A. actinomycetemcomitans were up to nine times higher and the mean total number of cultivable bacteria per sample higher (P <0.01) in AMI-GCP than in non-AMI-GCP. CONCLUSION: The findings that no target subgingival species were overrepresented but the total bacterial number was higher in AMI-GCP than non-AMI-GCP patients may provide support to the hypothesis that elevated numbers of bacteria in close vicinity to sterile parenteral area present a risk for systemic health.

  • 6. Doğan, B
    et al.
    Kipalev, AS
    Okte, E
    Sultan, N
    Asikainen, Sirkka
    Umeå University, Faculty of Medicine, Odontology. Umeå University, Faculty of Medicine, Odontology.
    Consistent intrafamilial transmission of Actinobacillus actinomycetemcomitans despite clonal diversity.2008In: Journal of periodontology, ISSN 0022-3492, Vol. 79, no 2, 307-15 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Actinobacillus actinomycetemcomitans is a major pathogen in aggressive periodontitis. Our objectives were to determine the periodontal status and occurrence of A. actinomycetemcomitans in family members of subjects with A. actinomycetemcomitans-positive aggressive periodontitis (AgP) and to evaluate the probability of its intrafamilial transmission. METHODS: Of the 300 subjects screened, 66 (22%) had AgP and A. actinomycetemcomitans. Eleven (probands) of these 66 subjects with AgP met the strict inclusion criteria for the study. The study population consisted of 55 subjects, including probands and their family members (N = 44). Two family groups were formed according to whether the proband was a child (N = 7) or a parent (N = 4). Subgingival samples from all subjects were cultured for A. actinomycetemcomitans, and its clonal types were determined by combining serotype and genotype data for each isolate. RESULTS: Among 42 dentate family members, 16 (38%) exhibited periodontitis and eight (50%) had AgP. Periodontitis was found in nine of 12 (75%) of the dentate parents and six of 17 (35%) siblings of the child probands. A. actinomycetemcomitans was detected in 16 of 31 (52%) family members, i.e., one parent and at least one sibling in six families. The child probands shared A. actinomycetemcomitans clonal types with their parents in five of six (83%) families and with their siblings in three of six (50%) families. In the four parent-proband families, A. actinomycetemcomitans occurred in two spouses and all nine children. The parent probands shared A. actinomycetemcomitans clonal types with their spouses in both families and with their children in three of four families. In all families, the likelihood of intrafamilial transmission of A. actinomycetemcomitans was statistically significant. Members of most families (eight of 11, 73%) also harbored additional clonal types of A. actinomycetemcomitans. CONCLUSION: Parents and siblings of an individual with A. actinomycetemcomitans-positive AgP may have an increased susceptibility to periodontitis and shared and/or other clonal types of oral A. actinomycetemcomitans.

  • 7. Fujise, O
    et al.
    Lakio, L
    Wang, Y
    Asikainen, Sirkka
    Umeå University, Faculty of Medicine, Odontology, Oral Microbiology.
    Chen, C
    Clonal distribution of natural competence in Actinobacillus actinomycetemcomitans.2004In: Oral Microbiology and Immunology, ISSN 0902-0055, E-ISSN 1399-302X, Vol. 19, no 5, 340-342 p.Article in journal (Refereed)
    Abstract [en]

    The competence for natural transformation was investigated in 67 Actinobacillus actinomycetemcomitans strains. The transformation assays were performed with both cloned DNA fragments and chromosomal markers of A. actinomycetemcomitans. Competence was found in 12 of 18 serotype a strains, 0 of 21 serotype b strains, 0 of 14 serotype c strains, 3 of 6 serotype d strains, 3 of 4 serotype e strains, 0 of 3 serotype f strains, and 0 of 1 nonserotypeable strain. The transformation frequencies varied from 5 x 10(-3) to 4 x 10(-6) (median 1.5 x 10(-4)). The distribution pattern of natural competence is concordant with the major clonal lineages of A. actinomycetemcomitans. Serotype a strains are predominantly competent for transformation, while serotypes b and c strains are apparently non-competent.

  • 8.
    Hedberg, Maria
    et al.
    Umeå University, Faculty of Medicine, Odontology, Oral Microbiology.
    Asikainen, Sirkka
    Umeå University, Faculty of Medicine, Odontology, Oral Microbiology.
    Growth inhibition of Porphyromonas gingivalis biofilm by lactobacilli2007Report (Other academic)
    Abstract [en]

    Background. Chronic periodontitis is one of the most common infectious diseases of the oral cavity. Dental plaque contains a mix of oral bacteria, and grows as biofilm on tooth surfaces. One of the bacterial species associated with periodontitis is Porphyromonas gingivalis, a Gram-negative anaerobic rod. Lactobacilli are used in probiotic products and are known to play an important role in the management of health by stimulating the immune system and contributing to the balance of the normal microflora. The knowledge of probiotic effects on oral bacteria is at present limited.

    Purpose. Lactobacillus reuteri, and Lactobacillus acidophilus are two species used in different probiotic products. In the presence of glycerol L. reuteri produces an antimicrobial product, 3-hydroxypropionaldehyd, also called reuterin. The purpose of the study was to examine the impact of L. reuteri and L. acidophilus on biofilm formed by P. gingivalis.

    Methods. To study whether L. reuteri and L. acidophilus had ability to alter the biofilm formation of P. gingivalis, 108 CFU/mL P. gingivalis and 108 CFU/mL of one of the lactobacilli were co-cultured in Brucella broth using cell-culture plates. After 48 h incubation the broth was removed and the biofilm studied by microscopy, crystal violet staining with subsequent absorbance measurements at 590 nm. Viable bacterial cells were determined in the biofilm and in the removed growth medium.

    Results. P. gingivalis and L. reuteri cultured individually formed heavy layers of biofilm (A590=2.1-3.1), whereas L. acidophilus gave a very thin layer (A590=0.21-0.35). In the biofilm competition assay, the level of viable P. gingivalis cells were reduced by at least 3 logs regardless the addition of glycerol when co-cultured with L. reuteri or L. acidophilus. In presence of glycerol, both P. gingivalis and L. reuteri were reduced below the detection level after 48 h incubation.

    Even though P. gingivalis cultured as single species formed a dense biofilm this was strongly reduced when co-cultured with L. acidophilus.

    Conclusion. In summary, the observed glycerol-dependent growth inhibition of P. gingivalis by L. reuteri seemed to be due to reuterin production. Competition in the biofilm model appeared to favor both lactobacillus species tested at the expense of P. gingivalis. The lactobacilli were able to strongly inhibit or suppress the growth of a major periodontal pathogen in the biofilm-competition assay.

  • 9.
    Hedberg, Maria
    et al.
    Umeå University, Faculty of Medicine, Odontology, Oral Microbiology.
    Karched, Maribasappa
    Asikainen, Sirkka
    Umeå University, Faculty of Medicine, Odontology, Oral Microbiology.
    In-vitro growth inhibition of periodontitis-associated species by Lactobacillus reuteri2006Report (Other academic)
    Abstract [en]

    Purpose. Lactobacillus reuteri, a species used in probiotic products, produces in vitro a bacteriocin, reuterin, in the presence of glycerol. The purpose of the study was to investigate in vitro whether L. reuteri strains inhibit the growth of periodontal pathogens.

    Methods. The inhibition study was based on a disk-diffusion method. The periodontitis-associated bacteria were pre-grown for 20 h in Brucella broth or Brucella blood agar at 37oC in anaerobic atmosphere. Standardization of bacterial inocula used in the assay was made by determinations of optical density, microscopic counting of cells, and viable count. Brucella blood agar plates, without or with glycerol (100 mM), were seeded with standardized inocula of the periodontal pathogens Fusobacterium nucleatum (IDH 4186), Porphyromonas gingivalis (ATCC 33277), Prevotella intermedia (ATCC 25611), and Actinobacillus actinomycetemcomitans (SA 1398). The lactobacilli L. reuteri ATCC 55730 and L. reuteri PTA 5289 were grown for 16 h in MRS broth. A 20-L aliquot of the suspension containing 107 CFU/mL was used to soak 6-mm paper disks, which were placed on Brucella agar plates (diameter 14 cm), seeded with each periodontal pathogen separately. The plates were then incubated for 3 - 7 days in anaerobic atmosphere at 37oC before measuring the inhibition zones.

    Results. On Brucella blood agar plates seeded with periodontal pathogens, no inhibition zones were seen around the paper discs. When glycerol was added to the agar, zones of 26 to 118 mm appeared. Sizes of the zones depended on the L. reuteri strain, the periodontal pathogen, and the sizes of their inocula. L. reuteri PTA 5289 had a stronger (7-30%) inhibitory effect than L. reuteri ATCC 55730 on all periodontal species. P. gingivalis was the most susceptible species among the tested strains.

    Conclusion. Both L. reuteri strains strongly inhibited or suppressed the growth of the tested periodontitis-associated bacteria in the presence of glycerol. The inhibitory activity of L. reuteri PTA 5289 was consistently higher than that of L. reuteri ATCC 55730. The results suggest that the inhibition activity of the tested lactobacilli was related to reuterin.

  • 10. Ihalin, R
    et al.
    Asikainen, Sirkka
    Umeå University, Faculty of Medicine, Odontology, Oral Microbiology.
    16S rDNA PCR-denaturing gradient gel electrophoresis in determining proportions of coexisting Actinobacillus actinomycetemcomitans strains.2006In: Journal of Microbiological Methods, ISSN 0167-7012, E-ISSN 1872-8359, Vol. 65, no 3, 417-424 p.Article in journal (Refereed)
    Abstract [en]

    Certain serotypes of Actinobacillus actinomycetemcomitans seem to prefer coexistence in vivo. The 16S rDNA PCR-denaturing gradient gel electrophoresis (DGGE) was tested for its capability to distinguish coexisting A. actinomycetemcomitans strains of different serotypes or genetic lineages and to determine their proportions in vitro. The migration pattern of the PCR amplicon from serotype c differed from those of the other serotypes. Contrary to the strains of serotypes c, d, and e, strains of serotypes a, b, and f consistently demonstrated intra-serotype migration patterns similar to each other. Since the migration patterns differed between serotype c and b strains a strain of each was used to determine their proportional representation in a strain mixture. The strains were distinguishable from each other above the 5% PCR-DGGE detection level (12.5 ng DNA/1.5 x 10(6) cells). DGGE provides a promising tool for in vitro studies on the coexistence of different genetic lineages of A. actinomycetemcomitans.

  • 11.
    Ihalin, R
    et al.
    Umeå University, Faculty of Medicine, Odontology, Oral Microbiology.
    Karched, M
    Umeå University, Faculty of Medicine, Odontology, Oral Microbiology.
    Eneslätt, Kjell
    Umeå University, Faculty of Medicine, Odontology, Oral Microbiology.
    Asikainen, Sirkka
    Umeå University, Faculty of Medicine, Odontology, Oral Microbiology.
    Characterization of immunoaffinity purified peptidoglycan-associated lipoprotein of Actinobacillus actinomycetemcomitans.2006In: Journal of chromatography. B, ISSN 1570-0232, E-ISSN 1873-376X, Vol. 831, no 1-2, 116-125 p.Article in journal (Refereed)
    Abstract [en]

    Peptidoglycan-associated lipoprotein (PAL) is a highly conserved structural outer membrane protein among Gram-negative bacteria. In some species, it is proinflammatory and released extracellularly. We purified a newly identified PAL (AaPAL) of a periodontal pathogen Actinobacillus actinomycetemcomitans by using AaPAL antipeptide antibodies coupled to immunoaffinity chromatography column. No protein impurities originating in A. actinomycetemcomitans were found in the final product. Sera from patients infected by A. actinomycetemcomitans recognized the purified AaPAL. The present purification method seems to be suitable for isolation of AaPAL and probably PALs of other bacterial species, and applicable in studies investigating proinflammatory mechanisms of A. actinomycetemcomitans.

  • 12. Kanasi, E
    et al.
    Dogan, B
    Karched, M
    Thay, B
    Oscarsson, Jan
    Umeå University, Faculty of Medicine, Department of Odontology, Oral Microbiology.
    Asikainen, Sirkka
    Umeå University, Faculty of Medicine, Department of Odontology, Oral Microbiology.
    Lack of Serotype Antigen in A. actinomycetemcomitans2010In: Journal of Dental Research, ISSN 0022-0345, E-ISSN 1544-0591, Vol. 89, no 3, 292-6 p.Article in journal (Refereed)
    Abstract [en]

    Aggregatibacter actinomycetemcomitans is divided into 6 serotypes. Occurrence of non-serotypeable strains is known, but background reasons are unclear. We hypothesized that non-serotypeable strains represent new serotypes or have altered expression of serotype-specific polysaccharide antigen (S-PA). We first characterized 311 strains from 189 individuals using both immunoassay- and PCR-based serotyping. Next, using natural human infection and rabbit immunization approaches, we clarified whether the phenotypically non-serotypeable strains expressed S-PA. Immunoassay identified serotypes a-f among 216 strains from 159 individuals. The remaining 95 strains from 30 individuals were phenotypically non-serotypeable. Yet, all these strains were identified by PCR-typing as serotype a-, b-, c-, or f. Non-serotypeability was confirmed by Western immunoblot with respective rabbit antisera. Patient sera remained non-reactive with autologous non-serotypeable strains at the serotype-specific region. Rabbit immunization with a phenotypically non-serotypeable strain induced no antibody production against S-PA. Thus, phenotypically non-serotypeable strains did not include novel serotypes, but lacked S-PA expression.

  • 13.
    Karched, M
    et al.
    Umeå University, Faculty of Medicine, Odontology.
    Paul-Satyaseela, M
    Umeå University, Faculty of Medicine, Odontology.
    Asikainen, Sirkka
    Umeå University, Faculty of Medicine, Odontology, Oral Microbiology.
    A simple viability-maintaining method produces homogenic cell suspensions of autoaggregating wild-type Actinobacillus actinomycetemcomitans2007In: Journal of Microbiological Methods, ISSN 0167-7012, E-ISSN 1872-8359, Vol. 68, no 1, 46-51 p.Article in journal (Other (popular science, discussion, etc.))
    Abstract [en]

    Tenacious adherence and autoaggregation of wild-type Actinobacillus actinomycetemcomitans strains jeopardize reliability of determined cell concentrations, e.g. for studies on bacteria-host interactions. We first compared the efficacy of two methods, an indirect and a direct method, for homogenizing cell suspensions of a wild-type, autoaggregating (SA269) strain and of a non-autoaggregating laboratory variant (ATCC 43718) used as a reference. Since the direct method left visible clumps in SA269 suspension, only the indirect method was further tested. In serial dilutions of the homogenized cell suspensions of strains SA269 and ATCC 43718, the OD(600) values (R(2)=0.99, R(2)=0.99, respectively) and protein concentrations (R(2)=0.93, R(2)=0.95, respectively) correlated significantly (all P<0.002) with the dilution factor. There were no differences (P>0.05) in the bacterial viable counts between the two strains or between suspending solutions, i.e., PBS and water, the cell concentrations demonstrating 1x10(9) cells/ml at OD(600)=1. Repeated microscopic cell counts did not differ (P>0.05) from each other. Large aggregates occurred as 1% of cell units counted. Dispersing bacterial mass indirectly to solution leads to homogeneous cell suspensions with repeatable cell concentrations. Viability of A. actinomycetemcomitans was also maintained when cells were suspended in water.

  • 14.
    Karched, Maribasappa
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Ihalin, Rikka
    Eneslätt, Kjell
    Zhong, D
    Oscarsson, Jan
    Umeå University, Faculty of Medicine, Department of Odontology, Oral Microbiology.
    Wai, Sun Nyunt
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Chen, C
    Asikainen, Sirkka
    Umeå University, Faculty of Medicine, Department of Odontology.
    Vesicle-independent extracellular release of a proinflammatory outer membrane lipoprotein in free-soluble form2008In: BMC Microbiology, ISSN 1471-2180, E-ISSN 1471-2180, Vol. 28, no 8:18Article in journal (Refereed)
    Abstract [sv]

    Aggregatibacter actinomycetemcomitans is an oral bacterium associated with aggressively progressing periodontitis. Extracellular release of bacterial outer membrane proteins has been suggested to mainly occur via outer membrane vesicles. This study investigated the presence and conservation of peptidoglycan-associated lipoprotein (AaPAL) among A. actinomycetemcomitans strains, the immunostimulatory effect of AaPAL, and whether live cells release this structural outer membrane lipoprotein in free-soluble form independent of vesicles. RESULTS: The pal locus and its gene product were confirmed in clinical A. actinomycetemcomitans strains by PCR-restriction fragment length polymorphism and immunoblotting. Culturing under different growth conditions revealed no apparent requirement for the AaPAL expression. Inactivation of pal in a wild-type strain (D7S) and in its spontaneous laboratory variant (D7SS) resulted in pleiotropic cellular effects. In a cell culture insert model (filter pore size 0.02 um), AaPAL was detected from filtrates when strains D7S and D7SS were incubated in serum or broth in the inserts. Electron microscopy showed that A. actinomycetemcomitans vesicles (0.05-0.2 um) were larger than the filter pores and that there were no vesicles in the filtrates. The filtrates were immunoblot negative for a cytoplasmic marker, cyclic AMP (cAMP) receptor protein. An ex vivo model indicated cytokine production from human whole blood stimulated by AaPAL. CONCLUSIONS: Free-soluble AaPAL can be extracellularly released in a process independent of vesicles.

  • 15. Lakio, L
    et al.
    Lehto, M
    Tuomainen, AM
    Jauhiainen, M
    Malle, E
    Asikainen, Sirkka
    Umeå University, Faculty of Medicine, Odontology, Oral Microbiology.
    Pussinen, PJ
    Pro-atherogenic properties of lipopolysaccharide from the periodontal pathogen Actinobacillus actinomycetemcomitans.2006In: Journal of Endotoxin Research, ISSN 0968-0519, E-ISSN 1743-2839, Vol. 12, no 1, 57-64 p.Article in journal (Refereed)
    Abstract [en]

    An association between cardiovascular and periodontal disease may be due to lipopolysaccharide (LPS)-promoted release of inflammatory mediators, adverse alterations of the lipoprotein profile, and an imbalance in cholesterol homeostasis. Since periodontopathogenic potential differs between serotypes of a major periodontal pathogen, Actinobacillus actinomycetemcomitans, we studied the pro-atherogenic properties of LPS preparations from serotypes b and d strains on macrophages (RAW 264.7). A. actinomycetemcomitans LPS preparations induced a time-dependent release of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta). LPS induced foam cell formation and cholesteryl ester accumulation from native low density lipoprotein in the following order: A. actinomycetemcomitans strains JP2 (serotype b) > Y4 (serotype b) > IDH781 (serotype d). mRNA expression levels of scavenger receptor class B, type-I, and ATP-binding cassette transporter-1, receptors mediating cholesterol efflux from macrophages, were decreased by LPS preparations. The results suggest that the pro-atherogenic potential of A. actinomycetemcomitans LPS may depend on the infecting strain and correlate with the periodontopathogenic potential of the pathogen.

  • 16. Lakio, L
    et al.
    Paju, S
    Alfthan, G
    Tiirola, T
    Asikainen, Sirkka
    Umeå University, Faculty of Medicine, Odontology, Oral Microbiology.
    Pussinen, PJ
    Actinobacillus actinomycetemcomitans serotype d-specific antigen contains the O antigen of lipopolysaccharide.2003In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 71, no 9, 5005-5011 p.Article in journal (Refereed)
    Abstract [en]

    Actinobacillus actinomycetemcomitans is a gram-negative, facultatively anaerobic bacterium which is associated especially with aggressive forms of periodontitis. Contradictory results on the localization of the A. actinomycetemcomitans serotype-specific antigen have been reported. The aim of the present study was to characterize the A. actinomycetemcomitans serotype d-specific antigen. The antigen was isolated by affinity chromatography. The affinity column was prepared from immunoglobulin G isolated from rabbit antiserum raised against A. actinomycetemcomitans serotype d. The isolated antigen was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Western blotting, and silver staining, all of which revealed a ladder-like structure typical for the O antigen of lipopolysaccharide (LPS). In a displacement enzyme-linked immunosorbent assay (ELISA), the isolated antigen displaced in a concentration-dependent manner the binding of the polyclonal rabbit antiserum raised against A. actinomycetemcomitans serotype d to the competing whole-cell serotype d antigen. The isolated antigen contained LPS, and an equal concentration of LPS isolated from A. actinomycetemcomitans serotype d gave a similar displacement curve in the ELISA. In order to test the immunogenic properties of the isolated antigen, it was used to immunize a rabbit. The antiserum raised against the isolated antigen displayed specificity in Western blotting and ELISA similar to that of antibody raised against LPS isolated from A. actinomycetemcomitans serotype d. In conclusion, our results show that the A. actinomycetemcomitans serotype d-specific antigen contains the O-antigenic structure of LPS.

  • 17. Oittinen, J
    et al.
    Kurki, T
    Kekki, M
    Kuusisto, M
    Pussinen, P
    Vilkuna-Rautiainen, T
    Nieminen, A
    Asikainen, Sirkka
    Umeå University, Faculty of Medicine, Odontology, Oral Microbiology.
    Paavonen, J
    Periodontal disease and bacterial vaginosis increase the risk for adverse pregnancy outcome.2005In: Infectious diseases in obstetrics and gynecology, ISSN 1064-7449, E-ISSN 1098-0997, Vol. 13, no 4, 213-216 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To determine whether periodontal disease or bacterial vaginosis (BV) diagnosed before pregnancy increase the risk for adverse pregnancy outcome. METHODS: We enrolled a total of 252 women who had discontinued contraception in order to become pregnant. The first 130 pregnant women were included in the analyses. RESULTS: Multivariate analysis showed a strong association between periodontal disease and adverse pregnancy outcome (OR 5.5, 95% confidence interval 1.4-21.2; p = 0.014), and a borderline association between BV and adverse pregnancy outcome (OR 3.2, 95% confidence interval 0.9-10.7; p = 0.061). CONCLUSION: Our study suggests that pre-pregnancy counseling should include both oral and vaginal examinations to rule out periodontal disease and BV. This may ultimately have an impact on antenatal healthcare, and decrease the risk for adverse pregnancy outcome.

  • 18.
    Oscarsson, Jan
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, Oral Microbiology.
    Karched, Maribasappa
    Umeå University, Faculty of Medicine, Department of Odontology, Oral Microbiology.
    Thay, Bernard
    Umeå University, Faculty of Medicine, Department of Odontology, Oral Microbiology.
    Chen, Casey
    Asikainen, Sirkka
    Umeå University, Faculty of Medicine, Department of Odontology, Oral Microbiology.
    Proinflammatory effect in whole blood by free soluble bacterial components released from planktonic and biofilm cells2008In: BMC Microbiology, ISSN 1471-2180, E-ISSN 1471-2180, Vol. 8, no 206, 13- p.Article in journal (Refereed)
    Abstract [en]

    BackgroundAggregatibacter actinomycetemcomitans is an oral bacterium associated with aggressive forms of periodontitis. Increasing evidence points to a link between periodontitis and cardiovascular diseases, however, the underlying mechanisms are poorly understood. This study investigated the pathogenic potential of free-soluble surface material, released from live planktonic and biofilm A. actinomycetemcomitans cells.

    Results: By employing an ex vivo insert model (filter pore size 20 nm) we demonstrated that the A. actinomycetemcomitans strain D7S and its derivatives, in both planktonic and in biofilm life-form, released free-soluble surface material independent of outer membrane vesicles. This material clearly enhanced the production of several proinflammatory cytokines (IL-1β, TNF-α, IL-6, IL-8, MIP-1β) in human whole blood, as evidenced by using a cytokine antibody array and dissociation-enhanced-lanthanide-fluorescent-immunoassay. In agreement with this, quantitative real-time PCR indicated a concomitant increase in transcription of each of these cytokine genes. Experiments in which the LPS activity was blocked with polymyxin B showed that the stimulatory effect was only partly LPS-dependent, suggesting the involvement of additional free-soluble factors. Consistent with this, MALDI-TOF-MS and immunoblotting revealed release of GroEL-like protein in free-soluble form. Conversely, the immunomodulatory toxins, cytolethal distending toxin and leukotoxin, and peptidoglycan-associated lipoprotein, appeared to be less important, as evidenced by studying strain D7S cdt/ltx double, and pal single mutants. In addition to A. actinomycetemcomitans a non-oral species, Escherichia coli strain IHE3034, tested in the same ex vivo model also released free-soluble surface material with proinflammatory activity.

    ConclusionA. actinomycetemcomitans, grown in biofilm and planktonic form, releases free-soluble surface material independent of outer membrane vesicles, which induces proinflammatory responses in human whole blood. Our findings therefore suggest that release of surface components from live bacterial cells could constitute a mechanism for systemic stimulation and be of particular importance in chronic localized infections, such as periodontitis.

  • 19. Paino, Annamari
    et al.
    Tuominen, Heidi
    Jääskeläinen, Mari
    Alanko, Jonna
    Umeå University, Faculty of Medicine, Department of Odontology, Oral Microbiology.
    Nuutila, Jari
    Asikainen, Sirkka E
    Umeå University, Faculty of Medicine, Department of Odontology, Oral Microbiology.
    Pelliniemi, Lauri J
    Pöllänen, Marja T
    Chen, Casey
    Ihalin, Riikka
    Trimeric Form of Intracellular ATP Synthase Subunit β of Aggregatibacter actinomycetemcomitans Binds Human Interleukin-1β.2011In: PloS one, ISSN 1932-6203, Vol. 6, no 4, e18929- p.Article in journal (Refereed)
    Abstract [en]

    Bacterial biofilms resist host defenses and antibiotics partly because of their decreased metabolism. Some bacteria use proinflammatory cytokines, such as interleukin (IL)-1β, as cues to promote biofilm formation and to alter virulence. Although one potential bacterial IL-1β receptor has been identified, current knowledge of the bacterial IL-1β sensing mechanism is limited. In chronic biofilm infection, periodontitis, Aggregatibacter actinomycetemcomitans requires tight adherence (tad)-locus to form biofilms, and tissue destroying active lesions contain more IL-1β than inactive ones. The effect of IL-1β on the metabolic activity of A. actinomycetemcomitans biofilm was tested using alamarBlue™. The binding of IL-1β to A. actinomycetemcomitans cells was investigated using transmission electron microscopy and flow cytometry. To identify the proteins which interacted with IL-1β, different protein fractions from A. actinomycetemcomitans were run in native-PAGE and blotted using biotinylated IL-1β and avidin-HRP, and identified using mass spectroscopy. We show that although IL-1β slightly increases the biofilm formation of A. actinomycetemcomitans, it reduces the metabolic activity of the biofilm. A similar reduction was observed with all tad-locus mutants except the secretin mutant, although all tested mutant strains as well as wild type strains bound IL-1β. Our results suggest that IL-1β might be transported into the A. actinomycetemcomitans cells, and the trimeric form of intracellular ATP synthase subunit β interacted with IL-1β, possibly explaining the decreased metabolic activity. Because ATP synthase is highly conserved, it might universally enhance biofilm resistance to host defense by binding IL-1β during inflammation.

  • 20. Paju, S
    et al.
    Carlson, P
    Jousimies-Somer, H
    Asikainen, Sirkka
    Umeå University, Faculty of Medicine, Odontology, Oral Microbiology.
    Actinobacillus actinomycetemcomitans and Haemophilus aphrophilus in systemic and nonoral infections in Finland.2003In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 111, no 6, 653-657 p.Article in journal (Refereed)
    Abstract [en]

    The oral cavity is the ecological niche for Actinobacillus actinomycetemcomitans and Haemophilus aphrophilus, but occasionally they cause severe nonoral infections. In this study we present 20 systemic or nonoral infections due to A. actinomycetemcomitans and H. aphrophilus, comprising all isolates of these species forwarded to and stored in Finnish reference laboratories during the years 1988-2000. The time from specimen collection to correct species identification was 9.3 days for A. actinomycetemcomitans and 10.7 days for H. aphrophilus. A. actinomycetemcomitans strains represented serotypes a, b, c, and d. Arbitrarily primed PCR distinguished four A. actinomycetemcomitans and six H. aphrophilus genotypes. Antimicrobial susceptibility testing with benzylpenicillin, amoxicillin, tetracycline, metronidazole, azithromycin, and trovafloxacin showed generally good activities against the present strains, and the susceptibility patterns closely resembled those of oral strains. The prolonged time to recover and identify A. actinomycetemcomitans and H. aphrophilus from systemic and nonoral infections may delay the correct diagnosis of the patient, but the good antimicrobial efficacies of antimicrobial agents against these pathogens give a good prognosis for the patients and advance the treatment of severe infections caused by these fastidious organisms of oral origin.

  • 21. Paju, S
    et al.
    Pussinen, PJ
    Sinisalo, J
    Mattila, K
    Dogan, B
    Ahlberg, J
    Valtonen, V
    Nieminen, MS
    Asikainen, Sirkka
    Umeå University, Faculty of Medicine, Odontology, Oral Microbiology.
    Clarithromycin reduces recurrent cardiovascular events in subjects without periodontitis.2006In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 188, no 2, 412-419 p.Article in journal (Refereed)
    Abstract [en]

    Inflammation leading to acute coronary syndrome may be triggered by bacteria causing periodontal infection. We investigated if recurrence of cardiovascular events in unstable coronary patients are associated with periodontitis or microbiological/serological markers of it. Periodontitis-related parameters of 141 patients with acute non-Q-wave infarction or unstable angina pectoris, who participated in a double-blind, placebo-controlled study with clarithromycin for 3 months, were adjusted to the occurrence of a recurrent cardiovascular event during a follow-up period (average 519 days). In the age group under 65 years the patients with periodontitis had a univariate odds ratios (OR) 95% confidence intervals (95% CI) of 5.0 (1.02-24.55) for a recurrent cardiovascular event in comparison with patients without periodontitis. Dental status correlated positively with serum lipopolysaccharide concentrations and combined IgG antibody response to Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis. The end point frequency did not differ between clarithromycin and placebo groups in bacterium-positive, seropositive, or periodontitis patients. Fewer end points in clarithromycin group were seen in bacterium-negative, seronegative, edentulous, and non-periodontitis patients. Periodontitis and edentulousness are associated with recurrent cardiovascular events, especially in younger patients. Long-term clarithromycin therapy seems to be beneficial in prevention of recurrent cardiovascular events in non-periodontitis but not in periodontitis patients.

  • 22. Palikhe, A
    et al.
    Lokki, M-L
    Pussinen, P J
    Paju, S
    Ahlberg, J
    Asikainen, S
    Umeå University, Faculty of Medicine, Odontology. Umeå University, Faculty of Medicine, Odontology, Oral Microbiology.
    Seppänen, M
    Valtonen, V
    Nieminen, M S
    Sinisalo, J
    Lymphotoxin alpha LTA+496C allele is a risk factor for periodontitis in patients with coronary artery disease.2008In: Tissue Antigens, ISSN 0001-2815, E-ISSN 1399-0039, Vol. 71, no 6, 530-7 p.Article in journal (Refereed)
    Abstract [en]

    Periodontitis and coronary artery disease (CAD) are inflammatory diseases and associated with each other. The major histocompatibility complex (MHC) region carries genes involved in immune response and inflammation. We investigated whether the MHC genes correlate with the presence of periodontitis or with the occurrence of periodontal pathogens in patients with CAD. Blood and saliva samples from CAD patients (n = 106) were collected at the time of hospitalization. Nine MHC genetic markers [human leukocyte antigen (HLA)-A, HLA-B, HLA-DRB1, lymphotoxin alpha (LTA) +253(a/g), +496(C/T), +633(c/g), +724(C/A), C4A and C4B)] were typed. Based on panoramic tomography, patients were categorized into nonperiodontitis and periodontitis groups. Two major periodontal pathogens, Aggregatibacter (Actinobacillus) actinomycetemcomitans and Porphyromonas gingivalis, were cultivated and polymerase chain reaction-amplified from salivary samples. Serum immunoglobulin (Ig)A and IgG antibody levels to these pathogens were measured. In the univariate analysis, LTA+496C allele (OR = 5.29; 95% CI = 2.07-13.51, P = 0.00027), and the occurrence of P. gingivalis in saliva (OR = 4.74; 95% CI = 1.64-13.70; P = 0.002) were more frequent in periodontitis when compared with nonperiodontitis. Similarly, serum IgA antibody level against the pathogen was increased in periodontitis (P = 0.048). In the multiple logistic regression analysis, when a wide range of covariates was included, the LTA+496C allele (OR = 10.87; 95% CI = 3.23-36.60; P = 0.00012) and the elevated serum IgA antibody level against P. gingivalis (OR = 1.56; 95% CI = 1.05-2.30; P = 0.026) remained as significant risk factors for periodontitis. In conclusion, the major finding of this study is that the LTA+496C allele is associated with periodontitis in patients with CAD.

  • 23.
    Paul-Satyaseela, M
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, Oral Microbiology.
    Karched, M
    Umeå University, Faculty of Medicine, Department of Odontology, Oral Microbiology.
    Bian, Z
    Ihalin, R
    Umeå University, Faculty of Medicine, Department of Odontology, Oral Microbiology.
    Borén, Thomas
    Umeå University, Faculty of Medicine, Department of Odontology, Oral Microbiology. Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Arnqvist, Anna
    Umeå University, Faculty of Medicine, Department of Odontology, Oral Microbiology. Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Chen, C
    Asikainen, Sirkka
    Umeå University, Faculty of Medicine, Department of Odontology, Oral Microbiology.
    Immunoproteomics of Actinobacillus actinomycetemcomitans outer-membrane proteins reveal a highly immunoreactive peptidoglycan-associated lipoprotein.2006In: Journal of Medical Microbiology, ISSN 0022-2615, E-ISSN 1473-5644, Vol. 55, no 7, 931-942 p.Article in journal (Refereed)
    Abstract [en]

    In a search for novel bioactive cell surface structures of periodontal pathogens, it was found that sera from two patients with Actinobacillus actinomycetemcomitans-associated infections reacted strongly at 17 kDa on immunoblots of A. actinomycetemcomitans outer-membrane protein (OMP) preparations. The 17 kDa antigen was also recognized by anti-CsgA (Escherichia coli curli major subunit) antibody. The 17 kDa A. actinomycetemcomitans protein was identified as peptidoglycan-associated lipoprotein (PAL; AaPAL) by two-dimensional immunoblotting and subsequent sequence analysis by mass spectrometry and bioinformatics tools. AaPAL was an OMP and a lipoprotein, and it had an OmpA-like domain. In a group of middle-aged subjects (n = 26), serum reactivity to AaPAL was associated with the presence of periodontitis but not with the oral detection of A. actinomycetemcomitans. Both human sera and rabbit antisera against three different types of antigens, the gel-purified AaPAL, A. actinomycetemcomitans whole-cell antigens, and CsgA, recognized putative PALs of oral haemophili in addition to AaPAL. The results demonstrated that the novel AaPAL is a conserved bacterial lipoprotein. It is expressed in vivo and is strongly immunoreactive. The antigenic cross-reactivity found between AaPAL and oral haemophili may enhance local and systemic immuno-inflammatory reactions in periodontitis.

  • 24. Pussinen, PJ
    et al.
    Alfthan, G
    Reunanen, A
    Asikainen, Sirkka
    Umeå University, Faculty of Medicine, Odontology, Oral Microbiology.
    Knekt, P
    Antibodies to periodontal pathogens and stroke risk.2004In: Stroke; a journal of cerebral circulation, ISSN 1524-4628, Vol. 35, no 9, 2020-2023 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: The association between cerebrovascular events and periodontitis has been found in few studies based on clinical periodontal examinations. However, evidence on the association between periodontal pathogens and stroke is lacking. Therefore, the aim of the study was to investigate whether elevated levels of serum antibodies to major periodontal pathogens predict stroke in a case-control study. METHODS: The study population comprised 6950 subjects (aged 45 to 64 years) who participated in the Mobile Clinic Health Survey in 1973 to 1976 in Finland. During a follow-up of 13 years, a total of 173 subjects had a stroke. From these, 64 subjects had already experienced a stroke or had signs of coronary heart disease (CHD) at baseline, whereas 109 subjects were apparently healthy. Two controls per case were matched for age, gender, municipality, and disease status. Serum IgG and IgA class antibody levels to the periodontal pathogens, Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis, were determined by multiserotype enzyme-linked immunosorbent assay. RESULTS: The cases identified during the follow-up that were free of stroke or CHD at baseline were more often IgA-seropositive for A. actinomycetemcomitans than were their controls, 41.3% versus 29.3%. Compared with the seronegative, the seropositive subjects had a multivariate odds ratio of 1.6 (95% CI, 1.0 to 2.6) for stroke. The patients with a history of stroke or CHD at baseline were more often IgA-seropositive for P. gingivalis than were their controls, 79.7% versus 70.2%. When compared with the seronegative, the seropositive subjects had an odds ratio of 2.6 (1.0 to 7.0) for secondary stroke. CONCLUSIONS: The present prospective study provides serological evidence that an infection caused by major periodontal pathogens is associated with future stroke.

  • 25. Pussinen, PJ
    et al.
    Alfthan, G
    Tuomilehto, J
    Asikainen, Sirkka
    Umeå University, Faculty of Medicine, Odontology, Oral Microbiology.
    Jousilahti, P
    High serum antibody levels to Porphyromonas gingivalis predict myocardial infarction.2004In: European Journal of Cardiovascular Prevention & Rehabilitation, ISSN 1741-8267, E-ISSN 1741-8275, Vol. 11, no 5, 408-411 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: An association between coronary heart disease (CHD) and clinically diagnosed periodontitis has been found in several epidemiological studies. However, seroepidemiologic evidence based on prospective data on this association is totally lacking. DESIGN: The aim of the study was to investigate serum antibodies to major periodontal pathogens for their prediction of myocardial infarction (MI) in men free of CHD at baseline. METHODS: Cases and controls were ascertained from a random population sample of 4255 men aged 30 to 59 years at baseline. The study cases included 63 men with nonfatal MI or coronary death within the follow-up time of 10 years. Age-matched control subjects (n=63) were randomly chosen from the same cohort. Serum antibody levels to two major periodontopathogenic bacteria, Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis, were determined. RESULTS: There was no significant association between the risk for MI and IgG- or IgA-class antibody levels to A. actinomycetemcomitans or IgG-class antibody levels to P. gingivalis. However, a high P. gingivalis IgA-class antibody level predicted MI independently of classical cardiovascular risk factors. The risk for MI increased by increasing quartiles of antibody levels (P for the trend 0.021). Compared with the first quartile, the multivariate odds ratios of MI in the second, third and fourth quartiles were 2.47 (95% CI 0.75-8.11), 3.30 (1.03-10.58) and 3.99 (1.22-13.10), respectively. CONCLUSION: The study provides serological evidence that an infection caused by the periodontal pathogen, P. gingivalis, increases the risk for MI.

  • 26. Pussinen, PJ
    et al.
    Jauhiainen, M
    Vilkuna-Rautiainen, T
    Sundvall, J
    Vesanen, M
    Mattila, K
    Palosuo, T
    Alfthan, G
    Asikainen, Sirkka
    Umeå University, Faculty of Medicine, Odontology, Oral Microbiology.
    Periodontitis decreases the antiatherogenic potency of high density lipoprotein.2004In: Journal of Lipid Research, ISSN 0022-2275, E-ISSN 1539-7262, Vol. 45, no 1, 139-147 p.Article in journal (Refereed)
    Abstract [en]

    Periodontitis, a consequence of persistent bacterial infection and chronic inflammation, has been suggested to predict coronary heart disease (CHD). The aim of this study was to investigate the impact of periodontitis on HDL structure and antiatherogenic function in cholesterol efflux in vitro. HDL was isolated from 30 patients (age 43.6 +/- 6.1 years, mean +/- SD) with periodontitis before and after (3.2 +/- 1.4 months) periodontal treatment. The capacity of HDL for cholesterol efflux from macrophages (RAW 264.7), HDL composition, and key proteins of HDL metabolism were determined. After periodontal treatment, phospholipid transfer protein (PLTP) activity was 6.2% (P<0.05) lower, and serum HDL cholesterol concentration, PLTP mass, and cholesteryl ester transfer protein activity were 10.7% (P<0.001), 7.1% (P=0.078), and 19.4% (P<0.001) higher, respectively. The mean HDL2/HDL3 ratio increased from 2.16 +/- 0.87 to 3.56 +/- 0.48 (P<0.05). HDL total phospholipid mass and sphingomyelin-phosphatidylcholine ratio were 7.4% (P<0.05) and 36.8% (P<0.001) higher, respectively. The HDL-mediated cholesterol efflux tended to be higher after periodontal treatment; interestingly, this increase was significant (P<0.05) among patients whose C-reactive protein decreased (53.7% reduction, P=0.015) and who were positive by PCR for Actinobacillus actinomycetemcomitans. These results suggest that periodontitis causes similar, but milder, changes in HDL metabolism than those that occur during the acute-phase response and that periodontitis may diminish the antiatherogenic potency of HDL, thus increasing the risk for CHD.

  • 27. Pussinen, PJ
    et al.
    Jousilahti, P
    Alfthan, G
    Palosuo, T
    Asikainen, Sirkka
    Umeå University, Faculty of Medicine, Odontology, Oral Microbiology.
    Salomaa, V
    Antibodies to periodontal pathogens are associated with coronary heart disease.2003In: Arteriosclerosis, thrombosis, and vascular biology, ISSN 1524-4636, Vol. 23, no 7, 1250-1254 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: We analyzed the association of coronary heart disease (CHD) and serology of periodontitis in a random sample (n=1163) of men (aged 45 to 74 years) by determining serum IgG-antibodies to Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis. METHODS AND RESULTS: CHD (n=159) was more prevalent among edentulous than dentate subjects (19.8% and 12.1%, P=0.003). In the dentate population, CHD was more common among subjects seropositive for P. gingivalis compared with those seronegative (14.0% and 9.7%, P=0.029). Accordingly, CHD was more prevalent in subjects with a high combined antibody response than those with a low response (17.4% and 11.1%, P=0.026). When adjusted for age and several CHD risk factors, the subjects with a high combined antibody response had an odds ratio of 1.5 (95% CI, 0.95 to 2.50, P=0.077) for prevalent CHD. In a linear regression model, the combined antibody response was directly associated with prevalent CHD (P=0.046) and inversely with serum HDL cholesterol concentration (P=0.050). CONCLUSIONS: In conclusion, edentulousness and serum antibodies to major periodontal pathogens were associated with CHD. This suggests that periodontal infection or response of the host against the infection may play a role in the pathogenesis of CHD.

  • 28. Pussinen, PJ
    et al.
    Laatikainen, T
    Alfthan, G
    Asikainen, Sirkka
    Umeå University, Faculty of Medicine, Odontology, Oral Microbiology.
    Jousilahti, P
    Periodontitis is associated with a low concentration of vitamin C in plasma.2003In: Clinical and Diagnostic Laboratory Immunology, ISSN 1071-412X, Vol. 10, no 5, 897-902 p.Article in journal (Refereed)
    Abstract [en]

    This study aimed to clarify how concentrations of vitamin C in plasma relate to the serology of periodontitis. The random sample used comprised 431 men, 194 from Finland and 237 from Russia. The plasma vitamin C concentration was determined by o-phtaldialdehyde-fluorometry, and serum immunoglobulin G antibodies to Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis were determined by a multiserotype enzyme-linked immunosorbent assay (ELISA). The mean plasma vitamin C concentration was higher (P < 0.001) in Finnish subjects (mean +/- standard deviation, 4.5 +/- 2.8 mg/liter) than in Russian subjects (1.4 +/- 1.8 mg/liter). Mean antibody levels to both A. actinomycetemcomitans (4.7 +/- 3.6 versus 5.2 +/- 3.1 ELISA units [P = 0.05]) and P. gingivalis (5.7 +/- 2.5 versus 7.6 +/- 2.9 ELISA units [P < 0.001]) were lower in Finnish men than in Russian men. In the combined Finnish and Russian population, the antibody levels to P. gingivalis were negatively correlated with vitamin C concentrations (r = -0.22; P < 0.001); this association remained statistically significant (P = 0.010) in a linear regression model after adjustment for confounding factors. The proportion of P. gingivalis-seropositive subjects decreased with increasing vitamin C concentrations (P for trend, <0.01), but no trend was seen among A. actinomycetemcomitans-seropositive subjects. In conclusion, P. gingivalis infection is associated with low concentrations of vitamin C in plasma, which may increase colonization of P. gingivalis or disturb the healing of the infected periodontium.

  • 29. Pussinen, PJ
    et al.
    Vilkuna-Rautiainen, T
    Alfthan, G
    Palosuo, T
    Jauhiainen, M
    Sundvall, J
    Vesanen, M
    Mattila, K
    Asikainen, Sirkka
    Umeå University, Faculty of Medicine, Odontology, Oral Microbiology.
    Severe periodontitis enhances macrophage activation via increased serum lipopolysaccharide.2004In: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 24, no 11, 2174-2180 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: In periodontitis, overgrowth of Gram-negative bacteria and access of lipopolysaccharide (LPS) to circulation may activate macrophages leading to foam cell formation. We investigated whether periodontal treatment affects proatherogenic properties of low-density lipoprotein (LDL) and, thus, macrophage activation. METHODS AND RESULTS: LDL was isolated and characterized before and after treatment from 30 systemically healthy patients with periodontitis. Production of cytokines and LDL cholesteryl ester (LDL-CE) uptake by macrophages (RAW 264.7) was determined. Baseline periodontal variables correlated positively with serum LPS and C-reactive protein concentrations, as well as macrophage cytokine production and LDL-CE uptake. LPS concentration correlated positively with serum concentration of oxidized LDL and cytokine production. Higher cytokine production and LDL-CE uptake were induced by LDL isolated from patients with elevated number of affected teeth before treatment. Patients with serum LPS concentrations above the median (0.87 ng/mL) at baseline had higher serum high-density lipoprotein (HDL) cholesterol (baseline versus after treatment, 1.30+/-0.19 versus 1.48+/-0.28 mmol/L; P=0.002) and HDL/LDL ratio (0.31+/-0.01 versus 0.34+/-0.10; P=0.048), but lower serum LPS concentration (1.70+/-0.49 versus 0.98+/-0.50 ng/mL; P=0.004) and autoantibodies to beta2-glycoprotein I (0.11+/-0.06 versus 0.09+/-0.04 ELISA units; P=0.022) after treatment. CONCLUSIONS: Our results suggest that in systemically healthy patients, the infected/inflamed area in periodontitis is associated with macrophage activation via increased serum LPS concentration.

  • 30.
    Rompikuntal, Pramod Kumar
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Thay, Bernard
    Umeå University, Faculty of Medicine, Department of Odontology, Oral Microbiology.
    Khan, Muhammad Khanzeb
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Alanko, Jonna
    Umeå University, Faculty of Medicine, Department of Odontology, Oral Microbiology.
    Penttinen, Anna-Maija
    Umeå University, Faculty of Medicine, Department of Odontology, Oral Microbiology.
    Asikainen, Sirkka
    Umeå University, Faculty of Medicine, Department of Odontology, Oral Microbiology.
    Wai, Sun Nyunt
    Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Oscarsson, Jan
    Umeå University, Faculty of Medicine, Department of Odontology, Oral Microbiology.
    Perinuclear localization of internalized outer membrane vesicles carrying active cytolethal distending toxin (CDT) from aggregatibacter actinomycetemcomitans2012In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 80, no 1, 31-42 p.Article in journal (Refereed)
    Abstract [en]

    Aggregatibacter actinomycetemcomitans is implicated in aggressive forms of periodontitis. Similar to several other Gram-negative species this organism produces and excretes a cytolethal distending toxin (CDT), a genotoxin associated with cell distention, G(2) cell cycle arrest and/or apoptosis in many mammalian cell types. In this study we have identified A. actinomycetemcomitans outer membrane vesicles (OMVs) as a vehicle for simultaneous delivery of multiple proteins, including CDT into human cells. The OMV proteins were internalized in both HeLa cells and human gingival fibroblasts (HGF) via a mechanism of OMV fusion with lipid rafts in the plasma membrane. The active toxin unit, CdtB was localized inside the nucleus of the intoxicated cells, whereas OmpA and proteins detected using an antibody specific to whole A. actinomycetemcomitans serotype a cells had a perinuclear distribution. In accordance with a tight association of CdtB with OMVs, vesicles isolated from A. actinomycetemcomitans strain D7SS (serotype a) in contrast to OMVs from a D7SS cdtABC mutant induced a cytolethal distending effect on HeLa and HGF cells, indicating that OMV-associated CDT was biologically active. Association of CDT with OMVs was also observed in A. actinomycetemcomitans isolates, belonging to serotypes b, and c, respectively, indicating that OMV-mediated release of CDT may be conserved in A. actinomycetemcomitans. Although, the role of A. actinomycetemcomitans OMVs in periodontal disease has not yet been elucidated, our present data suggest that OMVs could deliver biologically active CDT and additional virulence factors into susceptible cells of the periodontium.

  • 31. Seppänen, M
    et al.
    Lokki, IL
    Notkola, LM
    Mattila, K
    Valtonen, V
    Nieminen, A
    Vesanen, M
    Asikainen, Sirkka
    Umeå University, Faculty of Medicine, Odontology, Oral Microbiology.
    Meri, S
    Complement and c4 null alleles in severe chronic adult periodontitis.2007In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 65, no 2, 176-181 p.Article in journal (Refereed)
    Abstract [en]

    Severe forms of chronic periodontitis affect up to 10% of adults. Tumour necrosis factor and lymphotoxin-alpha genes in the major histocompatibility complex are associated with severe periodontitis. Complement factor C4 is a nearby, polymorphic, functionally relevant gene region. Although associated with chronic mucosal infections, C4 deficiencies have not been assessed in adult periodontitis patients. We tested whether complement levels are systemically altered and C4 deficiencies associated with severe chronic periodontitis. In a case-control study, we analysed levels of plasma C3, and C4, serum classical pathway haemolytic activity, C4 allotypes and C4 gene numbers in 37 patients with severe chronic periodontitis and in 150 voluntary controls. Plasma levels of C3 were higher, and classical pathway haemolytic activity was lower in patients than in controls. Partial C4 gene deficiencies were more frequent in patients than in controls (odds ratio 2.4, 95% confidence interval 1.1-5.5, P = 0.032). Changes in complement levels may reflect chronic, recurring inflammation. C4 gene deficiencies are associated with predisposition to chronic periodontitis.

  • 32. Sun, Ruoxing
    et al.
    Kittichotirat, Weerayuth
    Wang, Justin
    Jan, Minnie
    Chen, Weizhen
    Asikainen, Sirkka
    Umeå University, Faculty of Medicine, Department of Odontology.
    Bumgarner, Roger
    Chen, Casey
    Genomic stability of aggregatibacter actinomycetemcomitans during persistent oral infection in human2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 6, e66472- p.Article in journal (Refereed)
    Abstract [en]

    The genome of periodontal pathogen Aggregatibacter actinomycetemcomitans exhibits substantial variations in gene content among unrelated strains primarily due to the presence or absence of genomic islands. This study examined the genomic stability of A. actinomycetemcomitans during its persistent infection in the same host. Four pairs of A. actinomycetemcomitans strains, each pair isolated from an individual over time (0-10 years), were examined for their gains/losses of genes by whole genome sequencing, comparative genomic hybridization by microarray and PCR analysis. Possible effects due to genomic changes were further assessed by comparative transcriptome analysis using microarrays. The results showed that each pair of strains was clonally identical based on phylogenetic analysis of 150 core genes. A novel 24.1-Kb plasmid found in strain S23A was apparently lost in the sibling strain I23C. A 353-bp inversion affecting two essential genes of the serotype-specific gene cluster was found in the serotype antigen-nonexpressing strain I23C, while the same gene cluster was intact in the serotype-expressing sibling strain S23A. A 2,293-bp deletion affecting a gene encoding oxaloacetate decarboxylase and its neighbor region was found in strain SCC2302 but not in the sibling strain AAS4a. However, no evidence of gains or losses of genomic islands was found in the paired strains. Transcriptome profiles showed little or no difference in the paired strains. In conclusion, the genome of A. actinomycetemcomitans appears to be relatively stable during short-term infection. Several types of genomic changes were observed in the paired strains of A. actinomycetemcomitans recovered from the same subjects, including a mutation in serotype-specific gene cluster that may allow the bacteria to evade host immune response.

  • 33. Vilkuna-Rautiainen, T
    et al.
    Pussinen, PJ
    Roivainen, M
    Petäys, T
    Jousilahti, P
    Hovi, T
    Vartiainen, E
    Asikainen, Sirkka
    Umeå University, Faculty of Medicine, Odontology, Oral Microbiology.
    Serum antibody response to periodontal pathogens and herpes simplex virus in relation to classic risk factors of cardiovascular disease.2006In: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 35, no 6, 1486-1494 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Increasing evidence links chronic infections, especially burden of several infections, with increased risk for cardiovascular diseases (CVD). We studied joint immune response against two major periodontal pathogens and herpes simplex virus (HSV) in relation to established risk factors of CVD. METHODS: Serum antibody levels to HSV, Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis were determined by ELISA. The study included 1107 subjects, 734 from Finland and 373 from Russia. RESULTS: Combined antibody response to periodontal pathogens was associated inversely (OR, 95% CI) with high-density lipoprotein (HDL) cholesterol concentration (beta = 0.35; 0.20, 0.60; P < 0.001) and directly with HSV antibody quartiles: compared with the first quartile, ORs (95% CI) for quartiles 2-4 were 1.43 (0.88-2.32), 1.74 (1.07-2.82), and 1.89 (1.18-3.02), respectively (P for trend <0.001), after adjusting for age, gender, area, education, smoking, BMI, alcohol, triglycerides, and number of teeth. In linear regression analysis, the 3-pathogen antibody score (comprising antibody levels against periodontal pathogens and HSV) was inversely associated with HDL cholesterol concentration (beta = -0.067/1 mmol/l; -0.235, -0.018; P < 0.05). CONCLUSIONS: HSV infection may promote infection by periodontal pathogens. Furthermore, the infectious burden comprising HSV and periodontitis may increase the risk for CVD by clearly decreasing HDL cholesterol concentrations.

  • 34. Yang, HW
    et al.
    Asikainen, Sirkka
    Umeå University, Faculty of Medicine, Odontology, Oral Microbiology.
    Dogan, B
    Suda, R
    Lai, CH
    Relationship of Actinobacillus actinomycetemcomitans serotype b to aggressive periodontitis: frequency in pure cultured isolates2004In: Journal of Periodontology, ISSN 0022-3492, E-ISSN 1943-3670, Vol. 75, no 4, 592-599 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: To our knowledge, the association of the five serotypes of Actinobacillus actinomycetemcomitans (A. actinomycetemcomitans) to the new diagnostic classification scheme defined by the American Academy of Periodontology in 1999 has not yet been described. The goal of this study was to characterize the frequencies of the five serotypes of A. actinomycetemcomitans in A. actinomycetemcomitans isolates from various forms of periodontitis using both old and new diagnostic classifications and to determine the relationships between serotype and age and clinical diagnosis. METHODS: A total of 345 A. actinomycetemcomitans isolates from 115 A. actinomycetemcomitans culture-positive subjects (mean age 38.0 +/- 18.3 years, 59% female) were collected. Based on the new classifications, 33 subjects had aggressive periodontitis and 82 chronic periodontitis. According to old classifications, there were six prepubertal periodontitis (PPP), 12 localized juvenile periodontitis (LJP), 15 post-localized juvenile periodontitis (PLJP), 28 refractory periodontitis (Ref-P), and 54 adult periodontitis (AP) cases. Serotypes of A. actinomycetemcomitans were determined by an indirect immunofluorescence assay using serotype-specific polyclonal antisera to A. actinomycetemcomitans strains ATCC 29523, ATCC 43728, ATCC 33384, IDH 781 and IDH 1705 (serotype a, b, c, d, and e, respectively). Proportions of serotype b were examined between different diagnostic and age groups with a Z-test for proportions. RESULTS: Most subjects (n = 100, 86.96%) were infected with a single serotype (22 serotype a, 44 serotype b, 30 serotype c, 1 serotype d, and 3 serotype e). There were 11 subjects (9.57%) with two serotypes and two subjects (1.74%) with 3 serotypes. Two individuals had isolates lacking any detectable serotype antigen. Serotype b was the predominant serotype in children under 18 years of age and young adults between 19 to 35 years, although serotype b status was not significantly associated with age. Serotypes d and e were not found in patients under 35 years old. In 62 adult patients, one subject had serotype d and three had serotype e. Serotype b was the most common serotype in aggressive periodontitis (60.61%). The proportion of cases with serotype b was significantly higher in aggressive periodontitis compared to chronic periodontitis (P = 0.031). Other serotypes were not significantly associated with new diagnostic categories. Serotypes d and e were not detected in aggressive periodontitis. CONCLUSION: The results of this study show that proportions of serotype b of A. actinomycetemcomitans are significantly greater in culture-positive patients with aggressive periodontitis than those with chronic periodontitis.

1 - 34 of 34
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf