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Oscarsson, Jan
Publications (10 of 25) Show all publications
Ahlstrand, T., Kovesjoki, L., Maula, T., Oscarsson, J. & Ihalin, R. (2019). Aggregatibacter actinomycetemcomitans LPS binds human interleukin-8. Journal of Oral Microbiology, 11(1)
Open this publication in new window or tab >>Aggregatibacter actinomycetemcomitans LPS binds human interleukin-8
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2019 (English)In: Journal of Oral Microbiology, ISSN 2000-2297, E-ISSN 2000-2297, Vol. 11, no 1Article in journal (Refereed) Published
Abstract [en]

Various gram-negative species sequester host cytokines using outer membrane proteins or surface modulation by sulfated polysaccharides. An outer membrane lipoprotein (BilRI) of the periodontal pathogen Aggregatibacter actinomycetemcomitans binds several cytokines, including interleukin (IL)-8. Because IL-8 is positively charged at physiological pH, we aimed to determine whether IL-8 interacts with negatively charged lipopolysaccharide (LPS). Binding was investigated using electrophoretic mobility shift assays and microwell-based time-resolved fluorometric immunoassay. LPS from each tested strain of A. actinomycetemcomitans (N = 13), Pseudomonas aeruginosa (N = 1) and Escherichia coli (N = 1) bound IL-8. The K-d value of the A. actinomycetemcomitans LPS-IL-8 interaction varied between 1.2-17 mu M irrespective of the serotype and the amount of phosphorus in LPS and was significantly lower than that of the BilRI-IL-8 interaction. Moreover, IL-8 interacted with whole A. actinomycetemcomitans cells and outer membrane vesicles. Hence, LPS might be involved in binding of IL-8 to the outer membrane of A. actinomycetemcomitans. This raises an interesting question regarding whether other gram-negative periodontal pathogens use LPS for IL-8 sequestering in vivo.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2019
Keywords
Lipopolysaccharides, host-pathogen interactions, chemokines, periodontal pathogen, bacterial rulence, outer membrane vesicles
National Category
Dentistry
Identifiers
urn:nbn:se:umu:diva-154325 (URN)10.1080/20002297.2018.1549931 (DOI)000451666300001 ()
Available from: 2018-12-18 Created: 2018-12-18 Last updated: 2018-12-18Bibliographically approved
Oscarsson, J. & Johansson, A. (2019). Comment from the Editor to the Special Issue: “Periodontitis: From Dysbiotic Microbial Immune Response to Systemic Inflammation”. Journal of Clinical Medicine, 8(10), Article ID 1706.
Open this publication in new window or tab >>Comment from the Editor to the Special Issue: “Periodontitis: From Dysbiotic Microbial Immune Response to Systemic Inflammation”
2019 (English)In: Journal of Clinical Medicine, ISSN 2077-0383, Vol. 8, no 10, article id 1706Article in journal, Editorial material (Other academic) Published
Abstract [en]

The human oral cavity contains a large number of different microbial habitats. When microbes from the oral indigenous flora colonize the interspace between the tooth and the connective tissue, they induce an inflammatory response. If the microbes are in sufficient numbers, and release components that cause an imbalance in the host inflammatory response, degenerative processes in the surrounding tissues are induced, ultimately resulting in periodontal disease. The disease progress depends on bacterial load, the composition of the microbial community, and host genetic factors. The two most studied periodontal pathogens, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans express virulence factors, including proteases and exotoxins. Periodontal infections are also linked to the risk pattern of several systemic diseases. We would like to shed light on the mechanisms behind periodontitis and the associations of periodontal infections with systemic inflammation. Seven articles are included in this Special Issue and cover several pathogenic processes in the periodontal infection with capacity to cause imbalance in the host response. Highlights from each of the published papers are summarized and discussed below.

Place, publisher, year, edition, pages
Basel, Switzerland: MDPI, 2019
Keywords
periodontitis, cardiovascular diseases, rheumatoid arthritis, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, inflammatory response
National Category
Medical Biotechnology
Research subject
Infectious Diseases
Identifiers
urn:nbn:se:umu:diva-164304 (URN)10.3390/jcm8101706 (DOI)31623278 (PubMedID)
Available from: 2019-10-21 Created: 2019-10-21 Last updated: 2019-10-24Bibliographically approved
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
Lindholm, M., Aung, K. M., Wai, S. N. & Oscarsson, J. (2019). Role of OmpA1 and OmpA2 in Aggregatibacter actinomycetemcomitans and Aggregatibacter aphrophilus serum resistance. Journal of Oral Microbiology, 11(1), Article ID 1536192.
Open this publication in new window or tab >>Role of OmpA1 and OmpA2 in Aggregatibacter actinomycetemcomitans and Aggregatibacter aphrophilus serum resistance
2019 (English)In: Journal of Oral Microbiology, ISSN 2000-2297, E-ISSN 2000-2297, Vol. 11, no 1, article id 1536192Article in journal (Refereed) Published
Abstract [en]

Aggregatibacter actinomycetemcomitans and Aggregatibacter aphrophilus belong to the HACEK group of fastidious Gram-negative organisms, a recognized cause of infective endocarditis. A. actinomycetemcomitans is also implicated in aggressive forms of periodontitis. We demonstrated that A. aphrophilus strains, as A. actinomycetemcomitans are ubiquitously serum resistant. Both species encode two Outer membrane protein A paralogues, here denoted OmpA1 and OmpA2. As their respective pangenomes contain several OmpA1 and OmpA2 alleles, they represent potential genotypic markers. A naturally competent strain of A. actinomycetemcomitans and A. aphrophilus, respectively were used to elucidate if OmpA1 and OmpA2 contribute to serum resistance. Whereas OmpA1 was critical for survival of A. actinomycetemcomitans D7SS in 50% normal human serum (NHS), serum resistant ompA1 mutants were fortuitously obtained, expressing enhanced levels of OmpA2. Similarly, OmpA1 rather than OmpA2 was a major contributor to serum resistance of A. aphrophilus HK83. Far-Western blot revealed that OmpA1AA, OmpA2AA, and OmpA1AP can bind to C4-binding protein, an inhibitor of classical and mannose-binding lectin (MBL) complement activation. Indeed, ompA1 mutants were susceptible to these pathways, but also to alternative complement activation. This may at least partly reflect a compromised outer membrane integrity but is also consistent with alternative mechanisms involved in OmpA-mediated serum resistance.

Place, publisher, year, edition, pages
Taylor & Francis, 2019
Keywords
Aggregatibacter actinomycetemcomitans, Aggregatibacter aphrophilus, serum resistance, outer membrane protein A
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-153103 (URN)10.1080/20002297.2018.1536192 (DOI)000448422100001 ()2-s2.0-85055581204 (Scopus ID)
Available from: 2018-11-07 Created: 2018-11-07 Last updated: 2018-11-07Bibliographically 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
Belibasakis, G. N., Maula, T., Bao, K., Lindholm, M., Bostanci, N., Oscarsson, J., . . . Johansson, A. (2019). Virulence and Pathogenicity Properties of Aggregatibacter actinomycetemcomitans. Pathogens, 8(4), Article ID E222.
Open this publication in new window or tab >>Virulence and Pathogenicity Properties of Aggregatibacter actinomycetemcomitans
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2019 (English)In: Pathogens, ISSN 2076-0817, Vol. 8, no 4, article id E222Article in journal (Refereed) Published
Abstract [en]

Aggregatibacter actinomycetemcomitans is a periodontal pathogen colonizing the oral cavity of a large proportion of the human population. It is equipped with several potent virulence factors that can cause cell death and induce or evade inflammation. Because of the large genetic diversity within the species, both harmless and highly virulent genotypes of the bacterium have emerged. The oral condition and age, as well as the geographic origin of the individual, influence the risk to be colonized by a virulent genotype of the bacterium. In the present review, the virulence and pathogenicity properties of A. actinomycetemcomitans will be addressed.

Place, publisher, year, edition, pages
Basel: MDPI, 2019
Keywords
Aggregatibacter actinomycetemcomitans, biofilm, cytokine binding factors, cytolethal distending toxin, horizontal gene transfer, leukotoxin, lipopolysaccharides, outer membrane vesicles, proteomic
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-165083 (URN)10.3390/pathogens8040222 (DOI)31698835 (PubMedID)2-s2.0-85074732943 (Scopus ID)
Funder
Swedish Research Council, 2017-01198Västerbotten County Council, 7003193
Available from: 2019-11-09 Created: 2019-11-09 Last updated: 2019-11-26Bibliographically approved
Bao, K., Bostanci, N., Thurnheer, T., Grossmann, J., Wolski, W. E., Thay, B., . . . Oscarsson, J. (2018). Aggregatibacter actinomycetemcomitans H-NS promotes biofilm formation and alters protein dynamics of other species within a polymicrobial oral biofilm. npj Biofilms and Microbiomes, 4(12), 1-11
Open this publication in new window or tab >>Aggregatibacter actinomycetemcomitans H-NS promotes biofilm formation and alters protein dynamics of other species within a polymicrobial oral biofilm
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2018 (English)In: npj Biofilms and Microbiomes, ISSN 2055-5008, Vol. 4, no 12, p. 1-11Article in journal (Refereed) Published
Abstract [en]

Aggregatibacter actinomycetemcomitans is a Gram-negative organism, strongly associated with aggressive forms of periodontitis. An important virulence property of A. actinomycetemcomitans is its ability to form tenacious biofilms that can attach to abiotic as well as biotic surfaces. The histone-like (H-NS) family of nucleoid-structuring proteins act as transcriptional silencers in many Gram-negative bacteria. To evaluate the role of H-NS in A. actinomycetemcomitanshns mutant derivatives of serotype a strain D7S were generated. Characteristics of the hns mutant phenotype included shorter and fewer pili, and substantially lower monospecies biofilm formation relative to the wild type. Furthermore, the D7S hns mutant exhibited significantly reduced growth within a seven-species oral biofilm model. However, no apparent difference was observed regarding the numbers and proportions of the remaining six species regardless of being co-cultivated with D7S hnsor its parental strain. Proteomics analysis of the strains grown in monocultures confirmed the role of H-NS as a repressor of gene expression in A. actinomycetemcomitans. Interestingly, proteomics analysis of the multispecies biofilms indicated that the A. actinomycetemcomitanswild type and hns mutant imposed different regulatory effects on the pattern of protein expression in the other species, i.e., mainly Streptococcus spp., Fusobacterium nucleatum, and Veillonella dispar. Gene ontology analysis revealed that a large portion of the differentially regulated proteins was related to translational activity. Taken together, our data suggest that, apart from being a negative regulator of protein expression in A. actinomycetemcomitans, H-NS promotes biofilm formation and may be an important factor for survival of this species within a multispecies biofilm.

Place, publisher, year, edition, pages
Springer, 2018
Keywords
Aggregatibacter actinomycetemcomitans, H-NS, oral biofilm, oral microbiology, aggressive periodontitis, proteomics
National Category
Microbiology in the medical area
Research subject
Odontology
Identifiers
urn:nbn:se:umu:diva-148402 (URN)10.1038/s41522-018-0055-4 (DOI)
Available from: 2018-06-05 Created: 2018-06-05 Last updated: 2018-10-29Bibliographically approved
Ahlstrand, T., Tuominen, H., Beklen, A., Torittu, A., Oscarsson, J., Sormunen, R., . . . Ihalin, R. (2017). A novel intrinsically disordered outer membrane lipoprotein of Aggregatibacter actinomycetemcomitans binds various cytokines and plays a role in biofilm response to interleukin-1β and interleukin-8. Virulence, 8(2), 115-134
Open this publication in new window or tab >>A novel intrinsically disordered outer membrane lipoprotein of Aggregatibacter actinomycetemcomitans binds various cytokines and plays a role in biofilm response to interleukin-1β and interleukin-8
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2017 (English)In: Virulence, ISSN 2150-5594, E-ISSN 2150-5608, Vol. 8, no 2, p. 115-134Article in journal (Refereed) Published
Abstract [en]

Intrinsically disordered proteins (IDPs) do not have a well-defined and stable 3-dimensional fold. Some IDPs can function as either transient or permanent binders of other proteins and may interact with an array of ligands by adopting different conformations. A novel outer membrane lipoprotein, bacterial interleukin receptor I (BilRI) of the opportunistic oral pathogen Aggregatibacter actinomycetemcomitans binds a key gatekeeper proinflammatory cytokine interleukin (IL)-1β. Because the amino acid sequence of the novel lipoprotein resembles that of fibrinogen binder A of Haemophilus ducreyi, BilRI could have the potential to bind other proteins, such as host matrix proteins. However, from the tested host matrix proteins, BilRI interacted with neither collagen nor fibrinogen. Instead, the recombinant non-lipidated BilRI, which was intrinsically disordered, bound various pro/anti-inflammatory cytokines, such as IL-8, tumor necrosis factor (TNF)-α, interferon (IFN)-γ and IL-10. Moreover, BilRI played a role in the in vitro sensing of IL-1β and IL-8 because low concentrations of cytokines did not decrease the amount of extracellular DNA in the matrix of bilRI− mutant biofilm as they did in the matrix of wild-type biofilm when the biofilms were exposed to recombinant cytokines for 22 hours. BilRI played a role in the internalization of IL-1β in the gingival model system but did not affect either IL-8 or IL-6 uptake. However, bilRI deletion did not entirely prevent IL-1β internalization, and the binding of cytokines to BilRI was relatively weak. Thus, BilRI might sequester cytokines on the surface of A. actinomycetemcomitans to facilitate the internalization process in low local cytokine concentrations.

Keywords
Aggregatibacter actinomycetemcomitans, bacterial cytokine receptor, biofilm matrix composition, intrinsically disordered protein, outer membrane lipoprotein
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-131727 (URN)10.1080/21505594.2016.1216294 (DOI)000395377700002 ()27459270 (PubMedID)
Available from: 2017-02-20 Created: 2017-02-20 Last updated: 2018-06-09Bibliographically approved
Kieselbach, T. & Oscarsson, J. (2017). Dataset of the proteome of purified outer membrane vesicles from the human pathogen Aggregatibacter actinomycetemcomintans. Data in Brief, 10, 426-431
Open this publication in new window or tab >>Dataset of the proteome of purified outer membrane vesicles from the human pathogen Aggregatibacter actinomycetemcomintans
2017 (English)In: Data in Brief, ISSN 2352-3409, Vol. 10, p. 426-431Article in journal (Refereed) Published
Abstract [en]

Abstract The Gram-negative bacterium Aggregatibacter actinomycetemcomitans is an oral and systemic pathogen, which is linked to aggressive forms of periodontitis and can be associated with endocarditis. The outer membrane vesicles (OMVs) of this species contain effector proteins such as cytolethal distending toxin (CDT) and leukotoxin (LtxA), which they can deliver into human host cells. The OMVs can also activate innate immunity through NOD1- and NOD2-active pathogen-associated molecular patterns. This dataset provides a proteome of highly purified OMVs from A. actinomycetemcomitans serotype e strain 173. The experimental data do not only include the raw data of the LC-MS/MS analysis of four independent preparations of purified OMVs but also the mass lists of the processed data and the Mascot.dat files from the database searches. In total 501 proteins are identified, of which 151 are detected in at least three of four independent preparations. In addition, this dataset contains the COG definitions and the predicted subcellular locations (PSORTb 3.0) for the entire genome of A. actinomycetemcomitans serotype e strain SC1083, which is used for the evaluation of the LC-MS/MS data. These data are deposited in ProteomeXchange in the public dataset PXD002509. In addition, a scientific interpretation of this dataset by Kieselbach et al. (2015) [2] is available at http://dx.doi.org/10.1371/journal.pone.0138591.

Place, publisher, year, edition, pages
Elsevier, 2017
Keywords
Micobiology, Odontology, Periodontitis, Outer membrane vesicle, Proteomics
National Category
Chemical Sciences
Identifiers
urn:nbn:se:umu:diva-128946 (URN)10.1016/j.dib.2016.12.015 (DOI)28050585 (PubMedID)
Available from: 2016-12-20 Created: 2016-12-20 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
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