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Höglund-Åberg, Carola
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Publications (10 of 14) Show all publications
Johansson, A., Claesson, R., Höglund-Åberg, C., Haubek, D., Lindholm, M., Jasim, S. & Oscarsson, J. (2019). Genetic Profiling of Aggregatibacter actinomycetemcomitans Serotype B Isolated from Periodontitis Patients Living in Sweden. Pathogens, 8(3), 1-13, Article ID 153.
Open this publication in new window or tab >>Genetic Profiling of Aggregatibacter actinomycetemcomitans Serotype B Isolated from Periodontitis Patients Living in Sweden
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2019 (English)In: Pathogens, ISSN 2076-0817, Vol. 8, no 3, p. 1-13, article id 153Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Basel, Switzerland: MDPI, 2019
Keywords
Aggregatibacter actinomycetemcomitans; cagE; virB1; virB4; genotype; virulence
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject
Infectious Diseases
Identifiers
urn:nbn:se:umu:diva-163485 (URN)10.3390/pathogens8030153 (DOI)000488003600042 ()31533208 (PubMedID)
Available from: 2019-09-23 Created: 2019-09-23 Last updated: 2019-10-24Bibliographically approved
Oscarsson, J., Claesson, R., Lindholm, M., Höglund-Åberg, C. & Johansson, A. (2019). Tools of Aggregatibacter actinomycetemcomitans to Evade the Host Response. Journal of Clinical Medicine, 8(7), Article ID 1079.
Open this publication in new window or tab >>Tools of Aggregatibacter actinomycetemcomitans to Evade the Host Response
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2019 (English)In: Journal of Clinical Medicine, ISSN 2077-0383, Vol. 8, no 7, article id 1079Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Basel: MDPI, 2019
Keywords
Aggregatibacter actinomycetemcomitans, cytolethal distending toxin, invasiveness, leukotoxin, outer membrane vesicles, serum resistance
National Category
Medical Biotechnology
Research subject
Infectious Diseases
Identifiers
urn:nbn:se:umu:diva-161754 (URN)10.3390/jcm8071079 (DOI)31336649 (PubMedID)
Available from: 2019-07-25 Created: 2019-07-25 Last updated: 2019-07-29Bibliographically approved
Claesson, R., Höglund-Åberg, C., Haubek, D. & Johansson, A. (2017). Age-related prevalence and characteristics of Aggregatibacter actinomycetemcomitans in periodontitis patients living in Sweden. Journal of Oral Microbiology, 9, Article ID 1334504.
Open this publication in new window or tab >>Age-related prevalence and characteristics of Aggregatibacter actinomycetemcomitans in periodontitis patients living in Sweden
2017 (English)In: Journal of Oral Microbiology, ISSN 2000-2297, E-ISSN 2000-2297, Vol. 9, article id 1334504Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Taylor & Francis, 2017
Keywords
Aggregatibacter actinomycetemcomitans, leukotoxin, JP2, serotypes, AP-PCR genotypes, crobiological diagnostics
National Category
Microbiology in the medical area Dentistry
Identifiers
urn:nbn:se:umu:diva-137819 (URN)10.1080/20002297.2017.1334504 (DOI)000404392200001 ()
Available from: 2017-07-26 Created: 2017-07-26 Last updated: 2018-06-09Bibliographically approved
Johansson, A., Claesson, R., Höglund Åberg, C., Haubek, D. & Oscarsson, J. (2017). The cagE gene sequence as a diagnostic marker to identify JP2 and non-JP2 highly leukotoxic Aggregatibacter actinomycetemcomitans serotype b strains.. Journal of Periodontal Research, 52(5), 903-912
Open this publication in new window or tab >>The cagE gene sequence as a diagnostic marker to identify JP2 and non-JP2 highly leukotoxic Aggregatibacter actinomycetemcomitans serotype b strains.
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2017 (English)In: Journal of Periodontal Research, ISSN 0022-3484, E-ISSN 1600-0765, Vol. 52, no 5, p. 903-912Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
John Wiley & Sons, 2017
Keywords
Aggregatibacter actinomycetemcomitans, aggressive periodontitis, cagE, genotype, virulence, high leukotoxicity
National Category
Microbiology in the medical area
Research subject
Microbiology
Identifiers
urn:nbn:se:umu:diva-133592 (URN)10.1111/jre.12462 (DOI)000409224500011 ()28397250 (PubMedID)
Available from: 2017-04-12 Created: 2017-04-12 Last updated: 2018-06-09Bibliographically approved
Höglund Åberg, C., Kelk, P. & Johansson, A. (2015). Aggregatibacter actinomycetemcomitans: virulence of its leukotoxin and association with aggressive periodontitis. Virulence, 6(3), 188-195
Open this publication in new window or tab >>Aggregatibacter actinomycetemcomitans: virulence of its leukotoxin and association with aggressive periodontitis
2015 (English)In: Virulence, ISSN 2150-5608, Vol. 6, no 3, p. 188-195Article, review/survey (Refereed) Published
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.

Place, publisher, year, edition, pages
Taylor & Francis, 2015
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject
Infectious Diseases
Identifiers
urn:nbn:se:umu:diva-99665 (URN)10.4161/21505594.2014.982428 (DOI)000353286300004 ()25494963 (PubMedID)
Available from: 2015-04-18 Created: 2015-02-10 Last updated: 2018-06-07Bibliographically approved
Claesson, R., Gudmundson, J., Höglund-Åberg, C., Haubek, D. & Johansson, A. (2015). Detection of a 640-bp deletion in the Aggregatibacter actinomycetemcomitans leukotoxin promoter region in isolates from an adolescent of Ethiopian origin. Journal of Oral Microbiology, 7, Article ID 26974.
Open this publication in new window or tab >>Detection of a 640-bp deletion in the Aggregatibacter actinomycetemcomitans leukotoxin promoter region in isolates from an adolescent of Ethiopian origin
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2015 (English)In: Journal of Oral Microbiology, ISSN 2000-2297, E-ISSN 2000-2297, Vol. 7, article id 26974Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
CoAction Publishing, 2015
Keywords
Aggregatibacter actinomycetemcomitans, leukotoxicity, deletion, JP2, aggressive periodontitis, geographic spreading, Africa
National Category
Microbiology in the medical area Dentistry
Research subject
Microbiology
Identifiers
urn:nbn:se:umu:diva-101986 (URN)10.3402/jom.v7.26974 (DOI)000365696700001 ()25881573 (PubMedID)
Available from: 2015-04-18 Created: 2015-04-18 Last updated: 2018-06-07Bibliographically approved
Höglund Åberg, C., Haubek, D., Kwamin, F., Johansson, A. & Claesson, R. (2014). Leukotoxic activity of Aggregatibacter actinomycetemcomitans and periodontal attachment loss. PLoS ONE, 9(8), e104095
Open this publication in new window or tab >>Leukotoxic activity of Aggregatibacter actinomycetemcomitans and periodontal attachment loss
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2014 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 8, p. e104095-Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Public library science, 2014
Keywords
Aggregatibacter actinomycetemcomitans, leukotoxin (ltxA), periodontitis, attachment loss (AL)
National Category
Dentistry
Research subject
Odontology
Identifiers
urn:nbn:se:umu:diva-84192 (URN)10.1371/journal.pone.0104095 (DOI)000341357200065 ()25093857 (PubMedID)
Funder
Swedish Research Council
Note

Published in thesis in manuscript form with the title: Leukotoxic activity of Aggregatibacter actinomycetemcomitans.

Available from: 2013-12-17 Created: 2013-12-17 Last updated: 2018-06-08Bibliographically approved
Höglund Åberg, C., Kwamin, F., Claesson, R., Dahlén, G., Johansson, A. & Haubek, D. (2014). Progression of attachment loss is strongly associated with presence of the JP2 genotype of Aggregatibacter actinomycetemcomitans: a prospective cohort study of a young adolescent population. Journal of Clinical Periodontology, 41(3), 232-241
Open this publication in new window or tab >>Progression of attachment loss is strongly associated with presence of the JP2 genotype of Aggregatibacter actinomycetemcomitans: a prospective cohort study of a young adolescent population
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2014 (English)In: Journal of Clinical Periodontology, ISSN 0303-6979, E-ISSN 1600-051X, Vol. 41, no 3, p. 232-241Article in journal (Refereed) Published
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.

Keywords
A. actinomycetemcomitans, JP2 genotype, attachment loss, progression, leukotoxin, Ghana, periodontitis, adolescent
National Category
Dentistry
Research subject
Infectious Diseases
Identifiers
urn:nbn:se:umu:diva-83805 (URN)10.1111/jcpe.12209 (DOI)000330577300003 ()24304011 (PubMedID)
Funder
Swedish Research Council
Available from: 2013-12-08 Created: 2013-12-07 Last updated: 2018-06-08Bibliographically approved
Dahlén, G., Claesson, R., Höglund Åberg, C., Haubek, D., Johansson, A. & Kwamin, F. (2014). Subgingival bacteria in Ghanaian adolescents with or without progression of attachment loss. Journal of Oral Microbiology, 6, Article ID 23977.
Open this publication in new window or tab >>Subgingival bacteria in Ghanaian adolescents with or without progression of attachment loss
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2014 (English)In: Journal of Oral Microbiology, ISSN 2000-2297, E-ISSN 2000-2297, Vol. 6, article id 23977Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
CoAction Publishing, 2014
Keywords
subgingival bacteria, periodontitis, attachment loss, progression, adolescent, Ghana
National Category
Dentistry
Research subject
Microbiology
Identifiers
urn:nbn:se:umu:diva-88878 (URN)10.3402/jom.v6.23977 (DOI)000365673300001 ()24834145 (PubMedID)
Funder
Swedish Research Council
Available from: 2014-05-17 Created: 2014-05-17 Last updated: 2018-06-07Bibliographically approved
diva2:630551
Open this publication in new window or tab >>Cytolethal distending toxin in isolates of Aggregatibacter actinomycetemcomitans from Ghanaian adolescents and association with serotype and disease progression
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2013 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 6, p. e65781-Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Public Library Science, 2013
Keywords
Aggregatibacter actinomycetemcomitans, cytolethal distending toxin (Cdt), attachment loss (AL)
National Category
Dentistry
Research subject
Microbiology
Identifiers
urn:nbn:se:umu:diva-73249 (URN)10.1371/journal.pone.0065781 (DOI)000320363300043 ()23922633 (PubMedID)
Available from: 2013-06-19 Created: 2013-06-19 Last updated: 2018-06-08Bibliographically approved
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