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  • 1.
    Aberg, Carola Höglund
    et al.
    Umeå universitet, Medicinsk fakultet, Odontologi. Umeå universitet, Medicinsk fakultet, Odontologi, Parodontologi.
    Sjödin, Bengt
    Lakio, Laura
    Pussinen, Pirkko J
    Johansson, Anders
    Umeå universitet, Medicinsk fakultet, Odontologi. Umeå universitet, Medicinsk fakultet, Odontologi, Parodontologi.
    Claesson, Rolf
    Umeå universitet, Medicinsk fakultet, Odontologi. Umeå universitet, Medicinsk fakultet, Odontologi, Oral mikrobiologi.
    Presence of Aggregatibacter actinomycetemcomitans in young individuals: a 16-year clinical and microbiological follow-up study.2009Ingår i: Journal of clinical periodontology, ISSN 1600-051X, Vol. 36, nr 10, s. 815-22Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIM: To look for clinical signs of periodontal disease in young adults who exhibited radiographic bone loss and detectable numbers of Aggregatibacter actinomycetemcomitans in their primary dentition. MATERIAL AND METHODS: Periodontal status and radiographic bone loss were examined in each of the subjects 16 years after the baseline observations. Techniques for anaerobic and selective culture, and checkerboard, were used to detect periodontitis-associated bacterial species. The isolated A. actinomycetemcomitans strains were characterized by polymerase chain reaction. RESULTS: Signs of localized attachment loss were found in three out of the 13 examined subjects. A. actinomycetemcomitans was recovered from six of these subjects and two of these samples were from sites with deepened probing depths and attachment loss. Among the isolated A. actinomycetemcomitans strains, serotypes a-c and e, but not d or f, were found. None of the isolated strains belonged to the highly leucotoxic JP2 clone, and one strain lacked genes for the cytolethal distending toxin. CONCLUSIONS: This study indicates that the presence of A. actinomycetemcomitans and early bone loss in the primary dentition does not necessarily predispose the individual to periodontal attachment loss in the permanent dentition.

  • 2.
    Claesson, Rolf
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Chiang, Huei-Min
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Lindholm, Mark
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Höglund-Åberg, Carola
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Haubek, Dorte
    Aarhus University, Denmark.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Oscarsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Characterization of Aggregatibacter actinomycetemcomitans Serotype b Strains with Five Different, Including Two Novel, Leukotoxin Promoter Structures2020Ingår i: Vaccines, E-ISSN 2076-393X, Vol. 8, nr 3, artikel-id 398Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The JP2 genotype of A. actinomycetemcomitans, serotype b has attracted much interest during the past three decades due to its close association with periodontitis in young individuals and the enhanced expression of a leukotoxin (LtxA). A typical feature of this genotype is a 530-base pair (bp) deletion in the ltxCABD promoter region controlling leukotoxin expression. In the present work, we have characterized serotype b strains with four additional promoter types. Two novel types have been recognized, that is, one with a 230-bp deletion and one with a 172-bp duplication. Moreover, a strain with a 640-bp deletion and three strains with a full-length promoter, including the type strain Y4, were included in the present study. The seven strains were characterized by multi locus sequence typing (MLST) and arbitrarily primed polymerase chain reaction (PCR) and assessed for LtxA production. MLST showed that the strains with the non-JP2-like deletions represented distinct monophyletic groups, whereas the JP2 strain, HK1651, represented a separate branch. LtxA production was high in all three strains with a promoter deletion, whereas the other four strains showed significantly lower levels. It can be concluded that the genetic characterization and determination of LtxA production of A. actinomycetemcomitans isolates from individuals with periodontitis can contribute to the identification of novel virulent genotypes of this bacterium.

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  • 3.
    Claesson, Rolf
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Gudmundson, Jan
    Östersund, Sweden.
    Höglund-Åberg, Carola
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Haubek, Dorte
    Aarhus, Denmark.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Detection of a 640-bp deletion in the Aggregatibacter actinomycetemcomitans leukotoxin promoter region in isolates from an adolescent of Ethiopian origin2015Ingår i: Journal of Oral Microbiology, ISSN 2000-2297, E-ISSN 2000-2297, Vol. 7, artikel-id 26974Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The expression of the leukotoxin of Aggregatibacter actinomycetemcomitans is regulated by the leukotoxin promoter. A 530-bp deletion or an 886-bp insertion sequence (IS) element in this region has earlier been described in highly leukotoxic isolates. Here, we report on highly leukotoxic isolate with a 640-bp deletion, which was detected in an adolescent of Ethiopian origin.

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  • 4.
    Claesson, Rolf
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Höglund-Åberg, Carola
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Haubek, Dorte
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Age-related prevalence and characteristics of Aggregatibacter actinomycetemcomitans in periodontitis patients living in Sweden2017Ingår i: Journal of Oral Microbiology, ISSN 2000-2297, E-ISSN 2000-2297, Vol. 9, artikel-id 1334504Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The presence of Aggregatibacter actinomycetemcomitans in patients with periodontitis has been extensively studied for decades. Objective: To study the prevalence of A. actinomycetemcomitans in younger and older periodontitis patients and to genetically characterize isolates of this bacterium. Design: Data from microbiological analyses of 3459 subgingival plaque samples collected from 1445 patients, 337 'younger' patients (<= 35 yrs) and 1108 'older' patients (>35 yrs) during 15 years (2000-2014), has been summerized. Isolates of A. actinomycetemcomitans were serotyped, leukotoxin promoter typed (JP2 and non JP2) and arbitrarily primed PCR (APPCR) genotyped. The origin of the JP2 genotype detected in the study population was determined. Results: The prevalence of A. actinomycetemcomitans was higher among younger than older patients and samples from the younger patients contained higher proportions of the bacterium. Serotype b was more prevalent among younger patients and the majorty of these isolates was from the same AP-PCR genotype. The JP2 genotype was detected in 1.2% of the patients, and the majority of these carriers were of non-African origin. Conslusions: For presence and charcteristics of A. actinomycetemcomitans in clinical samples the age of the carriers were a discriminating factor. Additional, apparently non- African carriers of the JP2 genotype of A. actinomycetemcomitans were identified.

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  • 5.
    Claesson, Rolf
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Höglund-Åberg, Carola
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Esberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Haubek, Dorte
    Aarhus university, Denmark.
    Oscarsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Multilocus Sequence Typing of Non-JP2 Serotype b Aggregatibacter actinomycetemcomitans Strains of Ghanaian and Swedish Origin2021Ingår i: Frontiers in Cellular and Infection Microbiology, E-ISSN 2235-2988, Vol. 11, artikel-id 769671Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective and Methods: The Gram-negative bacterium, Aggregatibacter actinomycetemcomitans is associated with periodontitis affecting young individuals. The geographic dissemination of the highly leukotoxic JP2 genotype of serotype b of this species was previously studied by multilocus sequence typing (MLST). Here, we have used MLST to genetically characterize non-JP2 genotype strains of serotype b, isolated from individuals living in Ghana (n=41), and in Sweden (n=13), respectively.

    Results: The MLST analysis revealed a total of nine sequence types (ST). Both Ghanaian and Swedish isolates were distributed in ST 1-3. ST 5 and 6 were only identified among the Ghanaian strains, whereas ST 4, 7, 8 and 9 were uniquely represented among the Swedish strains. Previously, we characterized these non-JP2 genotype strains of A. actinomycetemcomitans serotype b by arbitrarily-primed (AP)-PCR, which distributed them into three groups, AP-PCR type 1, 2, and 3, respectively. AP-PCR type 1 strains are generally highly leukotoxic, and are associated with progression of periodontal attachment loss. As AP-PCR type 1 includes both JP2 genotype strains and a proportion of non-JP2 genotype strains of serotype b, a straightforward diagnostic procedure has been sought. This has revealed a gene, cagE, which appears to be conserved only in this AP-PCR type. According to our results, MLST was not a highly discriminatory method to identify AP-PCR type 1, as strains of this AP-PCR type could be found within three different ST: ST 2, ST 3 and ST 8.

    Conclusion: According to MLST, a geographic dissemination of non-JP2 genotype A. actinomycetemcomitans serotype b appears to exist. However, aiming to identify carriers of AP-PCR type 1, non-JP2 genotype serotype b, PCR with cagE-specific primers is likely the most efficient diagnostic procedure known today.

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  • 6.
    Claesson, Rolf
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Lagervall, Maria
    Department of Periodontology at Skanstull, Stockholm County Council, Stockholm, Sweden.
    Höglund-Åberg, Carola
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Haubek, Dorte
    Department of Pediatric Dentistry, School of Dentistry, Aarhus, Denmark.
    Detection of the highly leucotoxic JP2 clone of Aggregatibacter actinomycetemcomitans in members of a Caucasian family living in Sweden2011Ingår i: Journal of Clinical Periodontology, ISSN 0303-6979, E-ISSN 1600-051X, Vol. 38, nr 2, s. 115-121Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Carriers of the JP2 clone of Aggregatibacter actinomycetemcomitans exhibit an enhanced risk for developing aggressive periodontitis compared with individuals carrying non-JP2 clones. While the JP2 clone is almost exclusively detected among adolescents of African descent, reports on Caucasians colonized with the JP2 clone are remarkably few.

    Objective: The aim of this paper is to report on the history of periodontal disease and microbiological findings in a Caucasian family.

    Material and Methods: A. actinomycetemcomitans and other periodontitis-associated bacterial species in subgingival plaque samples were quantified by conventional culture technique. Leucotoxin promoter typing, serotyping and further characterizations of A. actinomycetemcomitans isolates were performed by PCR. DNA sequencing of the pseudogene, hbpA was performed to determine the origin of the detected JP2 clones. Further, genetically ancestry testing of family members was carried out.

    Results: The JP2 clone was detected in samples from two of the family members, a 33-year-old daughter and her 62-year-old mother. Relationship of their JP2 clones with JP2 clone strains from the Mediterranean area of Africa was indicated. Genotyping confirmed the Caucasian origin of all family members.

    Conclusions: Caucasian JP2 carriers exist and older subjects can carry the JP2 clone of A. actinomycetemcomitans.

  • 7.
    Dahlén, Gunnar
    et al.
    Göteborgs Universitet.
    Claesson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Höglund Åberg, Carola
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Tandläkarutbildning.
    Haubek, Dorte
    Aarhus University Denmark.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Tandläkarutbildning.
    Kwamin, Francis
    Ghana University, Ghana.
    Subgingival bacteria in Ghanaian adolescents with or without progression of attachment loss2014Ingår i: Journal of Oral Microbiology, ISSN 2000-2297, E-ISSN 2000-2297, Vol. 6, artikel-id 23977Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: This study describes subgingival bacterial profiles associated with clinical periodontal status in Ghanaian adolescents with or without progression of attachment loss.

    MATERIALS AND METHODS: Among 500 adolescents included in a cohort study, 397 returned 2 years later for a periodontal re-examination, including full-mouth CAL measurements. At follow-up, a subgroup of 98 adolescents was also subjected to bacterial sampling with paper points at four periodontal sites (mesial aspect of 11, 26, 31, and 46) and analyzed with the checkerboard DNA-DNA hybridization technique against DNA-probes from nine periodontitis-associated bacterial species.

    RESULTS: The 98 Ghanaian adolescents examined in the present study were similar to the entire group examined at the 2-year follow-up with respect to age, gender, and CAL ≥3 mm. A high detection frequency of Fusobacterium nucleatum and Prevotella intermedia (>99%) using checkerboard analysis was found, while for Aggregatibacter actinomycetemcomitans the detection frequency was <50%. A strong correlation was found at the individual level between the presence of P. intermedia and the total CAL change, and P. intermedia and Porphyromonas gingivalis were strongly correlated with a change in CAL and probing pocket depth (PPD) at the sampled sites. In a linear regression model, a significant discriminating factor for the total CAL change in the dentition during the 2-year follow-up period was obtained for P. intermedia and public school.

    CONCLUSION: This study indicates that subgingival bacterial species other than A. actinomycetemcomitans, for example, P. intermedia, have a significant association with periodontal breakdown (change in CAL) in Ghanaian adolescents with progression of periodontal attachment loss.

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    Dahlén
  • 8.
    Granlund, Margareta
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi.
    Höglund Åberg, Carola
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Claesson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Discrepancies in Antimicrobial Susceptibility between the JP2 and the Non-JP2 Genotype of Aggregatibacter actinomycetemcomitans2022Ingår i: Antibiotics, ISSN 0066-4774, E-ISSN 2079-6382, Vol. 11, nr 3, artikel-id 317Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The Aggregatibacter actinomycetemcomitans JP2 genotype is associated with high leukotoxin production and severe (aggressive) periodontitis. The aim of this study was to compare the antimicrobial susceptibility of JP2 and non-JP2 genotype strains. Minimal inhibitory concentrations (MICs) of 11 antimicrobials were determined for 160 A. actinomycetemcomitans of serotype a, b, or c, mostly isolated in Sweden or Ghana. MIC distributions for benzylpenicillin and fusidic acid revealed a more susceptible subpopulation for 38 serotype b strains, including the 32 of the JP2 genotype, with a benzylpenicillin MIC range of 0.125–0.5 mg/L. In contrast, benzylpenicillin MIC ≤ 16 mg/L was the estimated 99.5% epidemiological cutoff (ECOFF) of all strains. Beta-lactamase production was not detected. The fusidic acid MIC distribution of 11 strains of Aggregatibacter aphrophilus agreed with that found in non-JP2 strains. Cefotaxime, meropenem, levofloxacin, and trimethoprim–sulfamethoxazole MICs were all ≤0.25 mg/L, while MIC90 values for amoxicillin, azithromycin and tetracycline were 1 mg/L. Metronidazole MICs varied between 0.5 and >256 mg/L. The discrepant findings indicate that A. actinomycetemcomitans may be divided into two separate wild types, with a suggested intrinsic reduced susceptibility for benzylpenicillin in the majority of non-JP2 genotype strains. Possible implications for the treatment of A. actinomycetemcomitans infections are discussed.

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  • 9.
    Höglund Åberg, Carola
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Exotoxins of Aggregatibacter actinomycetemcomitans and periodontal attachment loss in adolescents2013Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Aggregatibacter actinomycetemcomitans is an oral bacterium that is mainly associated with aggressive forms of periodontitis, which most often starts at an early age. Amongst the virulence factors of A. actinomycetemcomitans, two exotoxins, the leukotoxin (LtxA) and the cytolethal distending toxin (Cdt), are suggested to play an important role in the pathogenicity of aggressive periodontitis. There is also a genetic diversity of the different strains of A. actinomycetemcomitans, and a variation in the ability of different strains to express and release exotoxins has been suggested. Of the different genotypes of A. actinomycetemcomitans, the highly leukotoxic JP2 genotype, which is prevalent in individuals of African origin, seems to be the genotype that is most strongly associated with localized aggressive periodontitis.

    This thesis is built upon studies of a West African adolescent population. The aim was to study the virulence characteristics of A. actinomycetemcomitans genotypes with a specific focus on the LtxA and the Cdt in relation to the progression of attachment loss (AL). The specific aim was first, to investigate cross-sectionally the presence of the JP2 and non-JP2 genotypes of A. actinomycetemcomitans in relation to the prevalence of AL and then prospectively to assess the progression of AL in a Ghanaian adolescent population. Second, in clinical isolates of A. actinomycetemcomitans obtained from the participants of the study, the serotypes and the virulence characteristics related to the two exotoxins were studied and associated with the progression of AL at the individual level.

    In Paper I, based on the study population consisting of 500 adolescents (mean age 13.2 years; SD ±1.5), it was shown that the overall carrier rate of A. actinomycetemcomitans was high (54.4%) and that the presence of this bacterium was associated with AL ≥ 3 mm. The JP2 genotype was prevalent (8.8%) in this population. In Paper II, 397 (79.4%) of the study participants were periodontally examined again at a 2-year follow-up. The presence of the JP2 genotype of A. actinomycetemcomitans in subgingival plaque was strongly associated with the progression of AL. This study also provided support for an enhanced estimated risk (odds ratio, OR=3.4), though less pronounced, for the progression of AL in individuals positive for the non-JP2 genotypes of A. actinomycetemcomitans.

    In Paper III, all three cdt genes (a, b and c) were detected in 79% of the examined A. actinomycetemcomitans isolates, all of which expressed an active toxin. The distribution of the cdt genes showed a serotype-dependent pattern. In particular, the presence of the b serotypes (both JP2 and non-JP2 genotypes) was associated with the disease progression, whereas the expression of Cdt was not particularly related to the disease progression.  In Paper IV, it was shown that the presence of of A. actinomycetemcomitans isolates with high leukotoxicity, also those of the non-JP2 genotypes of A. actinomycetemcomitans, were associated with an increased risk of the progression of AL in relation to the reference group. The main proportion of the serotype b isolates was distributed in the category of highly leukotoxic isolates. The analyses of the non-JP2 genotypes of serotype b indicated a diversity linked to the level of leukotoxicity.

    In conclusion, A. actinomycetemcomitans in general was associated with the progression of AL. Individuals with an increased risk of developing progression of AL mainly harboured isolates of A. actinomycetemcomitans with a high leukotoxicity, which suggests that the LtxA is an important virulence factor. Of the two exotoxins, the pathogenic potential was mainly associated with the LtxA, while the role of the Cdt is unclear.

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  • 10.
    Höglund Åberg, Carola
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Molekylär paradontologi.
    Antonoglou, Georgios
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Molekylär paradontologi.
    Haubek, Dorte
    Section for Pediatric Dentistry, Department of Dentistry, Health, Århus University, Århus, Denmark.
    Kwamin, Francis
    Dental School University of Ghana, Accra, Ghana.
    Claesson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Cytolethal distending toxin in isolates of Aggregatibacter actinomycetemcomitans from Ghanaian adolescents and association with serotype and disease progression 2013Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 8, nr 6, s. e65781-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and Objectives: The cytolethal distending toxin (Cdt) is a highly conserved exotoxin that are produced by a number of Gram negative bacteria, including Aggregatibacter actinomycetemcomitans, and affects mammalian cells by inhibiting cell division and causing apoptosis. A complete cdt-operon is present in the majority of A. actinomycetemcomitans, but the proportion of isolates that lack cdt-encoding genes (A, B and C) varies according to the population studied. The objectives of this study were to examine serotype, Cdt-genotype, and Cdt-activity in isolates of A. actinomycetemcomitans collected from an adolescent West African population and to examine the association between the carrier status of A. actinomycetemcomitans and the progression of attachment loss (AL).

    Material and Methods: A total of 249 A. actinomycetemcomitans isolates from 200 Ghanaian adolescents were examined for serotype and cdt-genotype by PCR. The activity of the Cdt-toxin was examined by DNA-staining of exposed cultured cells and documented with flow cytometry. The periodontal status of the participants was examined at baseline and at a two-year follow-up.

    Results: Presence of all three cdt-encoding genes was detected in 79% of the examined A. actinomycetemcomitans isolates. All these isolates showed a substantial Cdt-activity. The two different cdt-genotypes (with and without presence of all three cdt-encoding genes) showed a serotype-dependent distribution pattern. Presence of A. actinomycetemcomitans was significantly associated with progression of AL (OR = 5.126; 95% CI = [2.994 - 8.779], p < 0.001).

    Conclusion: A. actinomycetemcomitans isolated from the Ghanaian adolescents showed a distribution of serotype and cdt-genotype in line with results based on other previously studied populations. Presence of A. actinomycetemcomitans was significantly associated with disease progression, in particular the b serotype, whereas the association with disease progression was not particularly related to cdt-genotype, and Cdt-activity.

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    Cytolethal distending toxin in isolates of Aggregatibacter actinomycetemcomitans from Ghanaian adolescents and association with serotype and disease progression
  • 11.
    Höglund Åberg, Carola
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Haubek, Dorte
    Århus University.
    Kwamin, Francis
    Ghana University.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Claesson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Leukotoxic activity of Aggregatibacter actinomycetemcomitans and periodontal attachment loss2014Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 9, nr 8, s. e104095-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aggregatibacter actinomycetemcomitans is a Gram-negative periodontitis-associated bacterium that expresses a toxin that selectively affects leukocytes. This leukotoxin is encoded by an operon belonging to the core genome of this bacterial species. Variations in the expression of the leukotoxin have been reported, and a well-characterized specific clonal type (JP2) of this bacterium with enhanced leukotoxin expression has been isolated. In particular, the presence of the JP2 genotype significantly increases the risk for the progression of periodontal attachment loss (AL). Based on these findings we hypothesized that variations in the leukotoxicity are linked to disease progression in infected individuals. In the present study, the leukotoxicity of 239 clinical isolates of A. actinomycetemcomitans was analysed with different bioassays, and the genetic peculiarities of the isolates were related to their leukotoxicity based on examination with molecular techniques. The periodontal status of the individuals sampled for the presence of A. actinomycetemcomitans was examined longitudinally, and the importance of the observed variations in leukotoxicity was evaluated in relation to disease progression. Our data show that high leukotoxicity correlates with an enhanced risk for the progression of AL. The JP2 genotype isolates were all highly leukotoxic, while the isolates with an intact leukotoxin promoter (non-JP2 genotypes) showed substantial variation in leukotoxicity. Genetic characterization of the non-JP2 genotype isolates indicated the presence of highly leukotoxic genotypes of serotype b with similarities to the JP2 genotype. Based on these results, we conclude that A. actinomycetemcomitans harbours other highly virulent genotypes besides the previously described JP2 genotype. In addition, the results from the present study further highlight the importance of the leukotoxin as a key virulence factor in aggressive forms of periodontitis.

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  • 12.
    Höglund Åberg, Carola
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Kelk, Peyman
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Aggregatibacter actinomycetemcomitans: virulence of its leukotoxin and association with aggressive periodontitis2015Ingår i: Virulence, ISSN 2150-5608, Vol. 6, nr 3, s. 188-195Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Periodontitis is an infection-induced inflammatory disease that causes loss of the tooth supporting tissues. Much focus has been put on comparison of the microbial biofilm in the healthy periodontium with the diseased one. The information arising from such studies is limited due to difficulties to compare the microbial composition in these two completely different ecological niches. A few longitudinal studies have contributed with information that makes it possible to predict which individuals who might have an increased risk of developing aggressive forms of periodontitis, and the predictors are either microbial or/and host-derived factors. The most conspicuous condition that is associated with disease risk is the presence of Aggregatibacter actinomycetemcomitans at the individual level. This Gram-negative bacterium has a great genetic variation with a number of virulence factors. In this review we focus in particular on the leukotoxin that, based on resent knowledge, might be one of the most important virulence factors of A. actinomycetemcomitans.

  • 13.
    Höglund Åberg, Carola
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Kwamin, Francis
    Ghana University.
    Claesson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Dahlén, Gunnar
    Göteborgs Universitet.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Haubek, Dorte
    Århus Universitet, Danmark.
    Progression of attachment loss is strongly associated with presence of the JP2 genotype of Aggregatibacter actinomycetemcomitans: a prospective cohort study of a young adolescent population2014Ingår i: Journal of Clinical Periodontology, ISSN 0303-6979, E-ISSN 1600-051X, Vol. 41, nr 3, s. 232-241Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIM: To assess the progression of attachment loss (AL) during a two-year period according to the presence of JP2 and non-JP2 genotypes of A. actinomycetemcomitans in a Ghanaian adolescent population.

    METHODS: A total of 500 adolescents (mean age 13.2 years, SD± 1.5) were enrolled in the study. After two years, 397 (79.4%) returned for a periodontal re-examination, including the measurement of AL. The carrier status of the JP2 and non-JP2 genotypes of A. actinomycetemcomitans was evaluated in a baseline examination two years earlier.

    RESULTS: Individuals who carried the JP2 genotype of A. actinomycetemcomitans had a significantly increased risk (relative risk (RR) = 7.3) of developing AL ≥ 3 mm. The mean AL at the follow-up and the mean two-year progression of AL was significantly higher in the JP2 genotype-positive group (n=38) compared with the group positive for the non-JP2 genotypes of A. actinomycetemcomitans (n=169), and the group of A. actinomycetemcomitans-negative individuals (n=190). The JP2 genotype was strongly associated with the progression of AL ≥ 3 mm (OR= 14.3). The non-JP2 genotypes of A. actinomycetemcomitans were also, however less pronounced, associated with the progression of AL ≥ 3 mm (OR=3.4).

    CONCLUSION: The JP2 genotype of A. actinomycetemcomitans is strongly associated with the progression of AL.

  • 14.
    Höglund Åberg, Carola
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Molekylär paradontologi.
    Kwamin, Francis
    Univ Ghana, Sch Dent, Accra, Ghana.
    Claesson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Oral mikrobiologi.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Molekylär paradontologi. Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Oral mikrobiologi.
    Haubek, Dorte
    Århus Univ, Dept Dent, Århus, Denmark.
    Presence of JP2 and Non-JP2 genotypes of aggregatibacter actinomycetemcomitans and periodontal attachment loss in adolescents in Ghana2012Ingår i: Journal of Periodontology, ISSN 0022-3492, E-ISSN 1943-3670, Vol. 83, nr 12, s. 1520-1528Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Limited data are reported concerning the presence of A. actinomycetemcomitans and attachment loss (AL) in sub-Saharan countries. The authors investigate the carrier frequency of JP2 and non-JP2 genotypes of A. actinomycetemcomitans and the presence of AL in Ghanaian adolescents and evaluate socioeconomic conditions and oral hygiene practices. Methods: Five hundred individuals (mean +/- SD age: 13.2 +/- 1.5 years) in public and private schools were interviewed about demographic characteristics and oral hygiene practices and were given a full-mouth periodontal examination. Subgingival plaque samples were obtained from periodontal sites around permanent first molars and incisors. The carrier status of A. actinomycetemcomitans at the individual level was determined based on results obtained by cultivation and polymerase chain reaction. Results: The findings of this study show a relatively high carrier rate of JP2 and non-JP2 genotypes of Aggregatibacter actinomycetemcomitans in the Ghanaian adolescent population and the presence of this bacterium is associated with the occurrence of AL. The overall carrier rate of A. actinomycetemcomitans was 54.4%, and the highly leukotoxic JP2 genotype was detected in 8.8% of the study population. A total of 107 (21.4%) individuals had >= 1 tooth with AL >= 3 mm. The majority of the individuals carrying A. actinomycetemcomitans (80.1%) (P<0.001) and of the periodontally diseased individuals (91.6%) (P<0.001) were found in public schools. Conclusions: A. actinomycetemcomitans and AL were frequently found in Ghanaian adolescents. The school type was the strongest predictor of both presence of A. actinomycetemcomitans and AL.

  • 15.
    Johansson, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Claesson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Höglund Åberg, Carola
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Haubek, D.
    Oscarsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    The cagE gene sequence as a diagnostic marker to identify JP2 and non-JP2 highly leukotoxic Aggregatibacter actinomycetemcomitans serotype b strains.2017Ingår i: Journal of Periodontal Research, ISSN 0022-3484, E-ISSN 1600-0765, Vol. 52, nr 5, s. 903-912Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND AND OBJECTIVE:Aggregatibacter actinomycetemcomitans is involved in oral and systemic infections, and is associated with, eg aggressive forms of periodontitis and with endocarditis. The cagE gene encodes a ≈39 kDa putative exotoxin expressed by A. actinomycetemcomitans. The level of conservation of cagE, and its possible significance in periodontal disease, has not yet been thoroughly investigated. In the present study, the role of the cagE gene as a diagnostic marker has been investigated.

    MATERIAL AND METHODS:We have used conventional polymerase chain reaction (PCR), quantitative PCR and whole genome sequencing data to determine the prevalence of cagE in A. actinomycetemcomitans based on analysis of: (i) 249 isolates, collected and cultivated in a Ghanaian longitudinal cohort study; (ii) a serotype b collection of 19 strains; and (iii) the 36 A. actinomycetemcomitans genomes available in the NCBI database.

    RESULTS:Whereas cagE was absent in the other serotypes, our data support that this gene sequence is linked to a virulent and highly leukotoxic group of serotype b strains, including both JP2 and non-JP2 genotypes of A. actinomycetemcomitans.

    CONCLUSION:We propose that cagE has the potential to be used as a PCR-based gene marker for the identification of a virulent and highly leukotoxic group of serotype b strains, including both JP2 and non-JP2 genotypes. This finding might be of importance in the risk assessment of the development of periodontal attachment loss in young individuals and hence suggested to be a relevant discovery in future development of new diagnostic tools and/or treatment strategies.

  • 16.
    Johansson, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Claesson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Höglund-Åberg, Carola
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Haubek, Dorte
    Lindholm, Mark
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Jasim, Sarah
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Oscarsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Genetic Profiling of Aggregatibacter actinomycetemcomitans Serotype B Isolated from Periodontitis Patients Living in Sweden2019Ingår i: Pathogens, E-ISSN 2076-0817, Vol. 8, nr 3, s. 1-13, artikel-id 153Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The bacterium Aggregatibacter actinomycetemcomitans is associated with aggressive forms of periodontitis and with systemic diseases, such as endocarditis. By assessing a Ghanaian longitudinal adolescent cohort, we earlier recognized the cagE gene as a possible diagnostic marker for a subgroup of JP2 and non-JP2 genotype serotype b A. actinomycetemcomitans strains, associated with high leukotoxicity as determined in a semi-quantitative cell assay. This group of A. actinomycetemcomitans is associated with the progression of attachment loss. In the present work, we used conventional polymerase chain reaction (PCR) and quantitative PCR to perform the cagE genotyping of our collection of 116 selected serotype b A. actinomycetemcomitans strains, collected over a period of 15 years from periodontitis patients living in Sweden. The A. actinomycetemcomitans strains carrying cagE (referred to as cagE+; n = 49) were compared to the cagE-negative strains (n = 67), present at larger proportions in the subgingival plaque samples, and were also much more prevalent in the young (≤35 years) compared to in the old (>35 years) group of patients. Our present results underline the potential use of cagE genotyping in the risk assessment of the development of periodontal attachment loss in Swedish adolescents.

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  • 17.
    Lindholm, Mark
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Claesson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Löf, Hanna
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Chiang, Huei-Min
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Oscarsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Höglund-Åberg, Carola
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Radiographic and clinical signs of periodontitis and associated bacterial species in a Swedish adolescent population2023Ingår i: Journal of Periodontology, ISSN 0022-3492, E-ISSN 1943-3670, Vol. 94, nr 5, s. 630-640Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Periodontitis in adolescents has historically been rare in the Nordic countries but could be expected to increase due to changes in demographics. The primary aim was to cross-sectionally examine the presence of radiographic bone loss in adolescents in Västerbotten County, Sweden. The secondary aim was to compare periodontal and microbial parameters, as well as demographic patterns, in controls without bone loss with cases with bone loss.

    Methods: Adolescents born 2001 and who had a dental examination 2016 (n = 1656) were screened for proximal bone loss using bitewing radiographs taken during dental examinations (2014-2016). Individuals that exhibited proximal bone loss (> 2 mm) were invited to participate in a complete periodontal examination. Subgingival plaque and saliva were also sampled. For each adolescent with bone loss, two healthy individuals as controls were examined. Selected bacterial species in saliva and subgingival plaque were quantitatively examined by quantitative PCR. The subgingival plaque samples were also analysed with cultivation technique.

    Results: Proximal bone loss was identified in 24 individuals (1.45%) based on all the radiographs. Thirteen of these cases were periodontally examined and matched with 26 controls. Most cases were diagnosed with periodontitis (12/13 [92%]), whereas none of the controls had periodontitis. Higher concentrations and higher prevalence of the bacteria Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Filifactor alocis were generally found in the cases.

    Conclusion:The results suggest that periodontitis among adolescents, because of demographic differences (an increasingly heterogenous population), in Sweden is increasing and emphasizes the importance of radiographs for early detection of this disease.

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  • 18. Nørskov-Lauritsen, Niels
    et al.
    Claesson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Jensen, Anne Birkeholm
    Höglund Åberg, Carola
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Haubek, Dorte
    Aggregatibacter Actinomycetemcomitans: Clinical Significance of a Pathobiont Subjected to Ample Changes in Classification and Nomenclature2019Ingår i: Pathogens, E-ISSN 2076-0817, Vol. 8, nr 4, artikel-id 243Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Aggregatibacter actinomycetemcomitans is a Gram-negative bacterium that is part of the oral microbiota. The aggregative nature of this pathogen or pathobiont is crucial to its involvement in human disease. It has been cultured from non-oral infections for more than a century, while its portrayal as an aetiological agent in periodontitis has emerged more recently. A. actinomycetemcomitans is one species among a plethora of microorganisms that constitute the oral microbiota. Although A. actinomycetemcomitans encodes several putative toxins, the complex interplay with other partners of the oral microbiota and the suppression of host response may be central for inflammation and infection in the oral cavity. The aim of this review is to provide a comprehensive update on the clinical significance, classification, and characterisation of A. actinomycetemcomitans, which has exclusive or predominant host specificity for humans.

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  • 19.
    Oscarsson, Jan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Claesson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Lindholm, Mark
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Höglund-Åberg, Carola
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Tools of Aggregatibacter actinomycetemcomitans to Evade the Host Response2019Ingår i: Journal of Clinical Medicine, E-ISSN 2077-0383, Vol. 8, nr 7, artikel-id 1079Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Periodontitis is an infection-induced inflammatory disease that affects the tooth supporting tissues, i.e., bone and connective tissues. The initiation and progression of this disease depend on dysbiotic ecological changes in the oral microbiome, thereby affecting the severity of disease through multiple immune-inflammatory responses. Aggregatibacter actinomycetemcomitans is a facultative anaerobic Gram-negative bacterium associated with such cellular and molecular mechanisms associated with the pathogenesis of periodontitis. In the present review, we outline virulence mechanisms that help the bacterium to escape the host response. These properties include invasiveness, secretion of exotoxins, serum resistance, and release of outer membrane vesicles. Virulence properties of A. actinomycetemcomitans that can contribute to treatment resistance in the infected individuals and upon translocation to the circulation, also induce pathogenic mechanisms associated with several systemic diseases.

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  • 20.
    Razooqi, Zeinab
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Höglund-Åberg, Carola
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Kwamin, Francis
    Ghan university, Ghana, Accra.
    Claesson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Haubek, Dorte
    Jammerbugt Municipal Dental Service, Brovst, Denmark.
    Oscarsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Aggregatibacter actinomycetemcomitans and Filifactor alocis as associated with periodontal attachment loss in a cohort of ghanaian adolescents2022Ingår i: Microorganisms, E-ISSN 2076-2607, Vol. 10, nr 12, artikel-id 2511Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aims of the present study were to document the presence of Aggregatibacter actinomyctemcomitans and the emerging oral pathogen Filifactor alocis, as well as to identify genotypes of these bacterial species with enhanced virulence. In addition, these data were analyzed in relation to periodontal pocket depth (PPD) and the progression of PPD from the sampled periodontal sites during a two-year period. Subgingival plaque samples were collected from 172 periodontal pockets of 68 Ghanaian adolescents. PPD at sampling varied from 3–14 mm and the progression from baseline, i.e., two years earlier up to 8 mm. The levels of A. actinomycetemcomitans and F. alocis were determined with quantitative PCR. The highly leukotoxic JP2-genotype of A. actinomycetemcomitans and the ftxA a gene of F. alocis, encoding a putative Repeats-in-Toxin (RTX) protein, were detected with conventional PCR. The prevalence of A. actinomycetemcomitans was 57%, and 14% of the samples contained the JP2 genotype. F. alocis was detected in 92% of the samples and the ftxA gene in 52%. The levels of these bacterial species were significantly associated with enhanced PPD and progression, with a more pronounced impact in sites positive for the JP2 genotype or the ftxA gene. Taken together, the results indicate that the presence of both A. actinomycetemcomitans and F. alocis with their RTX proteins are linked to increased PPD and progression of disease.

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  • 21.
    Razooqi, Zeinab
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Tjellström, Ingeborg
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Höglund-Åberg, Carola
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Kwamin, Francis
    Ghana University, Accra, Ghana.
    Claesson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Haubek, Dorte
    Aarhus university, Aarhus, Denmark.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Oscarsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Association of Filifactor alocis and its RTX toxin gene ftxA with periodontal attachment loss, and in synergy with Aggregatibacter actinomycetemcomitans2024Ingår i: Frontiers in Cellular and Infection Microbiology, E-ISSN 2235-2988, Vol. 14, artikel-id 1376358Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The Gram-positive bacterium, Filifactor alocis is an oral pathogen, and approximately 50% of known strains encode a recently identified repeat-in-toxin (RTX) protein, FtxA. By assessing a longitudinal Ghanaian study population of adolescents (10-19 years of age; mean age 13.2 years), we recently discovered a possible correlation between deep periodontal pockets measured at the two-year follow-up, presence of the ftxA gene, and a high quantity of F. alocis. To further understand the contribution of F. alocis and FtxA in periodontal disease, we used qPCR in the present study to assess the carriage loads of F. alocis and the prevalence of its ftxA gene in subgingival plaque specimens, sampled at baseline from the Ghanaian cohort (n=500). Comparing these results with the recorded clinical attachment loss (CAL) longitudinal progression data from the two-year follow up, we concluded that carriers of ftxA-positive F. alocis typically exhibited higher loads of the bacterium. Moreover, high carriage loads of F. alocis and concomitant presence of the ftxA gene were two factors that were both associated with an enhanced prevalence of CAL progression. Interestingly, CAL progression appeared to be further promoted upon the simultaneous presence of F. alocis and the non-JP2 genotype of Aggregatibacter actinomycetemcomitans. Taken together, our present findings are consistent with the notion that F. alocis and its ftxA gene promotes CAL during periodontal disease.

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