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Aggregatibacter actinomycetemcomitans—Gram-Negative Bacterial Pathogen
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Aggregatibacter actinomycetemcomitans—Gram-Negative Bacterial Pathogen

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Bacterial Pathogens".

Deadline for manuscript submissions: closed (31 January 2020) | Viewed by 52060

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Dr. Anders Johansson

E-Mail Website
Guest Editor
Division of Molecular Periodontology, Department of Odontology, Faculty of Medicine, Umeå University, Umeå, Sweden
Interests: periodontal infection; Aggregatibacter actinomycetemcomitans; virulence mechanisms; pro-inflammatory response
Special Issues, Collections and Topics in MDPI journals
Prof. Joseph M. DiRienzo

E-Mail Website
Guest Editor
Department of Microbiology, University of Pennsylvania, Philadelphia, United States
Interests: Oral microbial pathogens; Gram-negative virulence factors; AB toxins; lipopolysaccharide.

Special Issue Information

Dear Colleagues,

Aggregatibacter actinomycetemcomitans, a member of the Gram-negative taxonomic family Pasteurellaceae, has attracted considerable attention as a potentially important pathogen in specific forms of periodontal disease and has earned a reputation as a member of the HACEK group of bacteria associated with some cases of infective endocarditis. The bacterium has acquired an impressive virulence-related armamentarium, including two well-characterized cytotoxins, exoenzymes, adhesins, and signaling molecules that promote its colonization and perturbation of the tissues, structural cells, and inflammatory cells of the human oral cavity. The focus of this Special Issue is on the properties and activities of A. actinomycetemcomitans that promote its function as an infectious agent, that is, its ability to target specific host populations, and define its interactions with specific mucosal tissues and cells. The objective is to present a complete picture of the participation of this bacterium in disease by presenting both in vitro and in vivo experimental and clinical studies. A comprehensive view of the contribution of this bacterium to mechanisms of infection and disease should also provide a basis for the development of new control strategies that move beyond the classical antibiotics.

Assoc. Prof. Anders Johansson
Prof. Joseph M. DiRienzo
Guest Editor

Manuscript Submission Information

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Keywords

  • Aggregatibacteria actinomycetemcomitans
  • leukotoxin
  • cytolethal distending toxin
  • epidemiology
  • periodontal pathogen
  • collagenase
  • biofilm
  • HACEK
  • systemic disease

Published Papers (15 papers)

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Editorial

Jump to: Research, Review, Other

5 pages, 193 KiB  
Editorial
Editorial Comments to the Special Issue: “Aggregatibacter actinomycetemcomitans—Gram-Negative Bacterial Pathogen”
by Jan Oscarsson, Joseph DiRienzo and Anders Johansson
Pathogens 2020, 9(6), 441; https://doi.org/10.3390/pathogens9060441 - 04 Jun 2020
Cited by 4 | Viewed by 1854
Abstract
Aggregatibacter actinomycetemcomitans is a periodontal pathogen colonizing the oral cavity in many individuals of the human population. It is equipped with several potent virulence factors that can cause cell death and induce or evade the host inflammatory response. Both harmless and highly virulent [...] Read more.
Aggregatibacter actinomycetemcomitans is a periodontal pathogen colonizing the oral cavity in many individuals of the human population. It is equipped with several potent virulence factors that can cause cell death and induce or evade the host inflammatory response. Both harmless and highly virulent genotypes of the bacterium have emerged because of the large genetic diversity within the species. 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 editorial, the different genetic and virulence properties of A. actinomycetemcomitans will be addressed in relation to the publications in this Special Issue. Full article
(This article belongs to the Special Issue Aggregatibacter actinomycetemcomitans—Gram-Negative Bacterial Pathogen)

Research

Jump to: Editorial, Review, Other

14 pages, 1785 KiB  
Article
Distinct Signaling Pathways Between Human Macrophages and Primary Gingival Epithelial Cells by Aggregatibacter actinomycetemcomitans
by Ellen S. Ando-Suguimoto, Manjunatha R. Benakanakere, Marcia P.A. Mayer and Denis F. Kinane
Pathogens 2020, 9(4), 248; https://doi.org/10.3390/pathogens9040248 - 27 Mar 2020
Cited by 12 | Viewed by 2736
Abstract
In aggressive periodontitis, the dysbiotic microbial community in the subgingival crevice, which is abundant in Aggregatibacter actinomycetemcomitans, interacts with extra- and intracellular receptors of host cells, leading to exacerbated inflammation and subsequent tissue destruction. Our goal was to understand the innate immune interactions [...] Read more.
In aggressive periodontitis, the dysbiotic microbial community in the subgingival crevice, which is abundant in Aggregatibacter actinomycetemcomitans, interacts with extra- and intracellular receptors of host cells, leading to exacerbated inflammation and subsequent tissue destruction. Our goal was to understand the innate immune interactions of A. actinomycetemcomitans with macrophages and human gingival epithelial cells (HGECs) on the signaling cascade involved in inflammasome and inflammatory responses. U937 macrophages and HGECs were co-cultured with A. actinomycetemcomitans strain Y4 and key signaling pathways were analyzed using real-time PCR, Western blotting and cytokine production by ELISA. A. actinomycetemcomitans infection upregulated the transcription of TLR2, TLR4, NOD2 and NLRP3 in U937 macrophages, but not in HGECs. Transcription of IL-1β and IL-18 was upregulated in macrophages and HGECs after 1 h interaction with A. actinomycetemcomitans, but positive regulation persisted only in macrophages, resulting in the presence of IL-1β in macrophage supernatant. Immunoblot data revealed that A. actinomycetemcomitans induced the phosphorylation of AKT and ERK1/2, possibly leading to activation of the NF-κB pathway in macrophages. On the other hand, HGEC signaling induced by A. actinomycetemcomitans was distinct, since AKT and 4EBP1 were phosphorylated after stimulation with A. actinomycetemcomitans, whereas ERK1/2 was not. Furthermore, A. actinomycetemcomitans was able to induce the cleavage of caspase-1 in U937 macrophages in an NRLP3-dependent pathway. Differences in host cell responses, such as those seen between HGECs and macrophages, suggested that survival of A. actinomycetemcomitans in periodontal tissues may be favored by its ability to differentially activate host cells. Full article
(This article belongs to the Special Issue Aggregatibacter actinomycetemcomitans—Gram-Negative Bacterial Pathogen)
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14 pages, 758 KiB  
Article
Chemical Composition, Antimicrobial activity, In Vitro Cytotoxicity and Leukotoxin Neutralization of Essential Oil from Origanum vulgare against Aggregatibacter actinomycetemcomitans
by Sanae Akkaoui, Anders Johansson, Maâmar Yagoubi, Dorte Haubek, Adnane El hamidi, Sana Rida, Rolf Claesson and OumKeltoum Ennibi
Pathogens 2020, 9(3), 192; https://doi.org/10.3390/pathogens9030192 - 05 Mar 2020
Cited by 12 | Viewed by 3240
Abstract
In this study, the essential oil of Origanum vulgare was evaluated for putative antibacterial activity against six clinical strains and five reference strains of Aggregatibacter actinomycetemcomitans, in comparison with some antimicrobials. The chemical composition of the essential oil was analyzed, using chromatography [...] Read more.
In this study, the essential oil of Origanum vulgare was evaluated for putative antibacterial activity against six clinical strains and five reference strains of Aggregatibacter actinomycetemcomitans, in comparison with some antimicrobials. The chemical composition of the essential oil was analyzed, using chromatography (CG) and gas chromatography–mass spectrometry coupled (CG–MS). The major compounds in the oil were Carvacrol (32.36%), α-terpineol (16.70%), p-cymene (16.24%), and Thymol (12.05%). The antimicrobial activity was determined by an agar well diffusion test. A broth microdilution method was used to study the minimal inhibitory concentration (MIC). The minimal bactericidal concentration (MBC) was also determined. The cytotoxicity of the essential oil (IC50) was <125 µg/mL for THP-1 cells, which was high in comparison with different MIC values for the A. actinomycetemcomitans strains. O. vulgare essential oil did not interfere with the neutralizing capacity of Psidium guajava against the A. actinomycetemcomitans leukotoxin. In addition, it was shown that the O. vulgare EO had an antibacterial effect against A. actinomycetemcomitans on a similar level as some tested antimicrobials. In view of these findings, we suggest that O.vulgare EO may be used as an adjuvant for prevention and treatment of periodontal diseases associated to A. actinomycetemcomitans. In addition, it can be used together with the previously tested leukotoxin neutralizing Psidium guajava. Full article
(This article belongs to the Special Issue Aggregatibacter actinomycetemcomitans—Gram-Negative Bacterial Pathogen)
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23 pages, 4526 KiB  
Article
Aggregatibacter actinomycetemcomitans LtxA Hijacks Endocytic Trafficking Pathways in Human Lymphocytes
by Edward T Lally, Kathleen Boesze-Battaglia, Anuradha Dhingra, Nestor M Gomez, Jinery Lora, Claire H Mitchell, Alexander Giannakakis, Syed A Fahim, Roland Benz and Nataliya Balashova
Pathogens 2020, 9(2), 74; https://doi.org/10.3390/pathogens9020074 - 21 Jan 2020
Cited by 5 | Viewed by 4338
Abstract
Leukotoxin (LtxA), from oral pathogen Aggregatibacter actinomycetemcomitans, is a secreted membrane-damaging protein. LtxA is internalized by β2 integrin LFA-1 (CD11a/CD18)-expressing leukocytes and ultimately causes cell death; however, toxin localization in the host cell is poorly understood and these studies fill this void. [...] Read more.
Leukotoxin (LtxA), from oral pathogen Aggregatibacter actinomycetemcomitans, is a secreted membrane-damaging protein. LtxA is internalized by β2 integrin LFA-1 (CD11a/CD18)-expressing leukocytes and ultimately causes cell death; however, toxin localization in the host cell is poorly understood and these studies fill this void. We investigated LtxA trafficking using multi-fluor confocal imaging, flow cytometry and Rab5a knockdown in human T lymphocyte Jurkat cells. Planar lipid bilayers were used to characterize LtxA pore-forming activity at different pHs. Our results demonstrate that the LtxA/LFA-1 complex gains access to the cytosol of Jurkat cells without evidence of plasma membrane damage, utilizing dynamin-dependent and presumably clathrin-independent mechanisms. Upon internalization, LtxA follows the LFA-1 endocytic trafficking pathways, as identified by co-localization experiments with endosomal and lysosomal markers (Rab5, Rab11A, Rab7, and Lamp1) and CD11a. Knockdown of Rab5a resulted in the loss of susceptibility of Jurkat cells to LtxA cytotoxicity, suggesting that late events of LtxA endocytic trafficking are required for toxicity. Toxin trafficking via the degradative endocytic pathway may culminate in the delivery of the protein to lysosomes or its accumulation in Rab11A-dependent recycling endosomes. The ability of LtxA to form pores at acidic pH may result in permeabilization of the endosomal and lysosomal membranes. Full article
(This article belongs to the Special Issue Aggregatibacter actinomycetemcomitans—Gram-Negative Bacterial Pathogen)
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19 pages, 2112 KiB  
Article
The Cell-Cycle Regulatory Protein p21CIP1/WAF1 Is Required for Cytolethal Distending Toxin (Cdt)-Induced Apoptosis
by Bruce J. Shenker, Lisa M. Walker, Ali Zekavat, Robert H. Weiss and Kathleen Boesze-Battaglia
Pathogens 2020, 9(1), 38; https://doi.org/10.3390/pathogens9010038 - 02 Jan 2020
Cited by 10 | Viewed by 3037
Abstract
The Aggregatibacter actinomycetemcomitans cytolethal distending toxin (Cdt) induces lymphocytes to undergo cell-cycle arrest and apoptosis; toxicity is dependent upon the active Cdt subunit, CdtB. We now demonstrate that p21CIP1/WAF1 is critical to Cdt-induced apoptosis. Cdt induces increases in the levels of p21 [...] Read more.
The Aggregatibacter actinomycetemcomitans cytolethal distending toxin (Cdt) induces lymphocytes to undergo cell-cycle arrest and apoptosis; toxicity is dependent upon the active Cdt subunit, CdtB. We now demonstrate that p21CIP1/WAF1 is critical to Cdt-induced apoptosis. Cdt induces increases in the levels of p21CIP1/WAF1 in lymphoid cell lines, Jurkat and MyLa, and in primary human lymphocytes. These increases were dependent upon CdtB’s ability to function as a phosphatidylinositol (PI) 3,4,5-triphosphate (PIP3) phosphatase. It is noteworthy that Cdt-induced increases in the levels of p21CIP1/WAF1 were accompanied by a significant decline in the levels of phosphorylated p21CIP1/WAF1. The significance of Cdt-induced p21CIP1/WAF1 increase was assessed by preventing these changes with a two-pronged approach; pre-incubation with the novel p21CIP1/WAF1 inhibitor, UC2288, and development of a p21CIP1/WAF1-deficient cell line (Jurkatp21−) using clustered regularly interspaced short palindromic repeats (CRISPR)/cas9 gene editing. UC2288 blocked toxin-induced increases in p21CIP1/WAF1, and JurkatWT cells treated with this inhibitor exhibited reduced susceptibility to Cdt-induced apoptosis. Likewise, Jurkatp21− cells failed to undergo toxin-induced apoptosis. The linkage between Cdt, p21CIP1/WAF1, and apoptosis was further established by demonstrating that Cdt-induced increases in levels of the pro-apoptotic proteins Bid, Bax, and Bak were dependent upon p21CIP1/WAF1 as these changes were not observed in Jurkatp21− cells. Finally, we determined that the p21CIP1/WAF1 increases were dependent upon toxin-induced increases in the level and activity of the chaperone heat shock protein (HSP) 90. We propose that p21CIP1/WAF1 plays a key pro-apoptotic role in mediating Cdt-induced toxicity. Full article
(This article belongs to the Special Issue Aggregatibacter actinomycetemcomitans—Gram-Negative Bacterial Pathogen)
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13 pages, 1679 KiB  
Article
Transcriptomic Analysis of Aggregatibacter actinomycetemcomitans Core and Accessory Genes in Different Growth Conditions
by Natalia O. Tjokro, Weerayuth Kittichotirat, Annamari Torittu, Riikka Ihalin, Roger E. Bumgarner and Casey Chen
Pathogens 2019, 8(4), 282; https://doi.org/10.3390/pathogens8040282 - 03 Dec 2019
Cited by 4 | Viewed by 2727
Abstract
Aggregatibacter actinomycetemcomitans genome can be divided into an accessory gene pool (found in some but not all strains) and a core gene pool (found in all strains). The functions of the accessory genes (genomic islands and non-island accessory genes) are largely unknown. We [...] Read more.
Aggregatibacter actinomycetemcomitans genome can be divided into an accessory gene pool (found in some but not all strains) and a core gene pool (found in all strains). The functions of the accessory genes (genomic islands and non-island accessory genes) are largely unknown. We hypothesize that accessory genes confer critical functions for A. actinomycetemcomitans in vivo. This study examined the expression patterns of accessory and core genes of A. actinomycetemcomitans in distinct growth conditions. We found similar expression patterns of island and non-island accessory genes, which were generally lower than the core genes in all growth conditions. The median expression levels of genomic islands were 29%–37% of the core genes in enriched medium but elevated to as high as 63% of the core genes in nutrient-limited media. Several putative virulence genes, including the cytolethal distending toxin operon, were found to be activated in nutrient-limited conditions. In conclusion, genomic islands and non-island accessory genes exhibited distinct patterns of expression from the core genes and may play a role in the survival of A. actinomycetemcomitans in nutrient-limited environments. Full article
(This article belongs to the Special Issue Aggregatibacter actinomycetemcomitans—Gram-Negative Bacterial Pathogen)
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9 pages, 4127 KiB  
Article
Aggregatibacter actinomycetemcomitans Biofilm Reduces Gingival Epithelial Cell Keratin Expression in an Organotypic Gingival Tissue Culture Model
by Arzu Beklen, Annamari Torittu, Riikka Ihalin and Marja Pöllänen
Pathogens 2019, 8(4), 278; https://doi.org/10.3390/pathogens8040278 - 01 Dec 2019
Cited by 6 | Viewed by 2382
Abstract
Epithelial cells express keratins, which are essential for the structural integrity and mechanical strength of the cells. In the junctional epithelium (JE) of the tooth, keratins such as K16, K18, and K19, are expressed, which is typical for non-differentiated and rapidly dividing cells. [...] Read more.
Epithelial cells express keratins, which are essential for the structural integrity and mechanical strength of the cells. In the junctional epithelium (JE) of the tooth, keratins such as K16, K18, and K19, are expressed, which is typical for non-differentiated and rapidly dividing cells. The expression of K17, K4, and K13 keratins can be induced by injury, bacterial irritation, smoking, and inflammation. In addition, these keratins can be found in the sulcular epithelium and in the JE. Our aim was to estimate the changes in K4, K13, K17, and K19 expression in gingival epithelial cells exposed to Aggregatibacter actinomycetemcomitans. An organotypic gingival mucosa and biofilm co-culture was used as a model system. The effect of the biofilm after 24 h was assessed using immunohistochemistry. The structure of the epithelium was also studied with transmission electron microscopy (TEM). The expression of K17 and K19, as well as total keratin expression, decreased in the suprabasal layers of epithelium, which were in close contact with the A. actinomycetemcomitans biofilm. The effect on keratin expression was biofilm specific. The expression of K4 and K13 was low in all of the tested conditions. When stimulated with the A. actinomycetemcomitans biofilm, the epithelial contact site displayed a thick necrotic layer on the top of the epithelium. The A. actinomycetemcomitans biofilm released vesicles, which were found in close contact with the epithelium. After A. actinomycetemcomitans irritation, gingival epithelial cells may lose their resistance and become more vulnerable to bacterial infection. Full article
(This article belongs to the Special Issue Aggregatibacter actinomycetemcomitans—Gram-Negative Bacterial Pathogen)
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9 pages, 959 KiB  
Article
Whole Genome Sequencing of Aggregatibacter actinomycetemcomitans Cultured from Blood Stream Infections Reveals Three Major Phylogenetic Groups Including a Novel Lineage Expressing Serotype a Membrane O Polysaccharide
by Signe Nedergaard, Carl M. Kobel, Marie B. Nielsen, Rikke T. Møller, Anne B. Jensen and Niels Nørskov-Lauritsen
Pathogens 2019, 8(4), 256; https://doi.org/10.3390/pathogens8040256 - 22 Nov 2019
Cited by 11 | Viewed by 2412
Abstract
Twenty-nine strains of Aggregatibacter actinomycetemcomitans cultured from blood stream infections in Denmark were characterised. Serotyping was unremarkable, with almost equal proportions of the three major types plus a single serotype e strain. Whole genome sequencing positioned the serotype e strain outside the species [...] Read more.
Twenty-nine strains of Aggregatibacter actinomycetemcomitans cultured from blood stream infections in Denmark were characterised. Serotyping was unremarkable, with almost equal proportions of the three major types plus a single serotype e strain. Whole genome sequencing positioned the serotype e strain outside the species boundary; moreover, one of the serotype a strains was unrelated to other strains of the major serotypes and to deposited sequences in the public databases. We identified five additional strains of this type in our collections. The particularity of the group was corroborated by phylogenetic analysis of concatenated core genes present in all strains of the species, and by uneven distribution of accessory genes only present in a subset of strains. Currently, the most accurate depiction of A. actinomycetemcomitans is a division into three lineages that differ in genomic content and competence for transformation. The clinical relevance of the different lineages is not known, and even strains excluded from the species sensu stricto can cause serious human infections. Serotyping is insufficient for characterisation, and serotypes a and e are not confined to specific lineages. Full article
(This article belongs to the Special Issue Aggregatibacter actinomycetemcomitans—Gram-Negative Bacterial Pathogen)
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14 pages, 1734 KiB  
Article
Differential Cell Lysis Among Periodontal Strains of JP2 and Non-JP2 Genotype of Aggregatibacter actinomycetemcomitans Serotype B Is Not Reflected in Dissimilar Expression and Production of Leukotoxin
by Anne Birkeholm Jensen, Marianne Lund, Niels Nørskov-Lauritsen, Anders Johansson, Rolf Claesson, Jesper Reinholdt and Dorte Haubek
Pathogens 2019, 8(4), 211; https://doi.org/10.3390/pathogens8040211 - 30 Oct 2019
Cited by 5 | Viewed by 2906
Abstract
Leukotoxic potential of Aggregatibacter actinomycetemcomitans strains has been studied by the use of several methods, and results differ depending on the methods used. The aim of the present study was to perform a comprehensive examination of the leukotoxic potential of a collection of [...] Read more.
Leukotoxic potential of Aggregatibacter actinomycetemcomitans strains has been studied by the use of several methods, and results differ depending on the methods used. The aim of the present study was to perform a comprehensive examination of the leukotoxic potential of a collection of A. actinomycetemcomitans strains by use of three quantitative methods, Western blotting, ELISA, and mRNA expression assay and compare these results with previous data obtained by a cell lysis assay. A higher leukotoxic potential among JP2 genotype strains compared to non-JP2 genotype strains of A. actinomycetemcomitans was found by Western blotting, ELISA and mRNA expression assay. Leukotoxicity as determined by cell lysis assay showed a variation among strains examined, not only depending on being part of JP2 genotype vs. non-JP2 genotype group of A. actinomycetemcomitans. The leukotoxicity of A. actinomycetemcomitans strains as determined by cell lysis assay did not correspond to the leukotoxic potential of A. actinomycetemcomitans strains as determined by three quantitative methods. A comparison of the results obtained by ELISA and mRNA expression assay showed a reasonable correlation between these two methods. It seems important to use more than one method to assess the LtxA-related virulence capacity of A. actinomycetemcomitans in order to obtain comprehensive understanding of the leukotoxic potential of A. actinomycetemcomitans strains. Full article
(This article belongs to the Special Issue Aggregatibacter actinomycetemcomitans—Gram-Negative Bacterial Pathogen)
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13 pages, 1015 KiB  
Article
Genetic Profiling of Aggregatibacter actinomycetemcomitans Serotype B Isolated from Periodontitis Patients Living in Sweden
by Anders Johansson, Rolf Claesson, Carola Höglund Åberg, Dorte Haubek, Mark Lindholm, Sarah Jasim and Jan Oscarsson
Pathogens 2019, 8(3), 153; https://doi.org/10.3390/pathogens8030153 - 17 Sep 2019
Cited by 13 | Viewed by 3242
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Aggregatibacter actinomycetemcomitans—Gram-Negative Bacterial Pathogen)
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Review

Jump to: Editorial, Research, Other

26 pages, 3075 KiB  
Review
Aggregatibacter, a Low Abundance Pathobiont That Influences Biogeography, Microbial Dysbiosis, and Host Defense Capabilities in Periodontitis: The History of a Bug, and Localization of Disease
by Daniel H. Fine, Helen Schreiner and Senthil Kumar Velusamy
Pathogens 2020, 9(3), 179; https://doi.org/10.3390/pathogens9030179 - 02 Mar 2020
Cited by 20 | Viewed by 3943
Abstract
Aggregatibacter actinomycetemcomitans, the focus of this review, was initially proposed as a microbe directly related to a phenotypically distinct form of periodontitis called localized juvenile periodontitis. At the time, it seemed as if specific microbes were implicated as the cause of distinct forms [...] Read more.
Aggregatibacter actinomycetemcomitans, the focus of this review, was initially proposed as a microbe directly related to a phenotypically distinct form of periodontitis called localized juvenile periodontitis. At the time, it seemed as if specific microbes were implicated as the cause of distinct forms of disease. Over the years, much has changed. The sense that specific microbes relate to distinct forms of disease has been challenged, as has the sense that distinct forms of periodontitis exist. This review consists of two components. The first part is presented as a detective story where we attempt to determine what role, if any, Aggregatibacter plays as a participant in disease. The second part describes landscape ecology in the context of how the host environment shapes the framework of local microbial dysbiosis. We then conjecture as to how the local host response may limit the damage caused by pathobionts. We propose that the host may overcome the constant barrage of a dysbiotic microbiota by confining it to a local tooth site. We conclude speculating that the host response can confine local damage by restricting bacteremic translocation of members of the oral microbiota to distant organs thus constraining morbidity and mortality of the host. Full article
(This article belongs to the Special Issue Aggregatibacter actinomycetemcomitans—Gram-Negative Bacterial Pathogen)
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18 pages, 1052 KiB  
Review
Aggregatibacter Actinomycetemcomitans: Clinical Significance of a Pathobiont Subjected to Ample Changes in Classification and Nomenclature
by Niels Nørskov-Lauritsen, Rolf Claesson, Anne Birkeholm Jensen, Carola Höglund Åberg and Dorte Haubek
Pathogens 2019, 8(4), 243; https://doi.org/10.3390/pathogens8040243 - 18 Nov 2019
Cited by 39 | Viewed by 6345
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Aggregatibacter actinomycetemcomitans—Gram-Negative Bacterial Pathogen)
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23 pages, 1403 KiB  
Review
Virulence and Pathogenicity Properties of Aggregatibacter actinomycetemcomitans
by Georgios N. Belibasakis, Terhi Maula, Kai Bao, Mark Lindholm, Nagihan Bostanci, Jan Oscarsson, Riikka Ihalin and Anders Johansson
Pathogens 2019, 8(4), 222; https://doi.org/10.3390/pathogens8040222 - 06 Nov 2019
Cited by 54 | Viewed by 8211
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Aggregatibacter actinomycetemcomitans—Gram-Negative Bacterial Pathogen)
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Other

9 pages, 422 KiB  
Case Report
JP2 Genotype of Aggregatibacter actinomycetemcomitans in Caucasian Patients: A Presentation of Two Cases
by Alexandra Stähli, Anton Sculean and Sigrun Eick
Pathogens 2020, 9(3), 178; https://doi.org/10.3390/pathogens9030178 - 01 Mar 2020
Cited by 8 | Viewed by 2167
Abstract
Aggregatibacter actinomycetemcomitans is a key pathogen that has been associated with periodontal disease. Its most important virulence factor is a leukotoxin capable of inactivating immune cells. The JP2 genotype of Aggregatibacter actinomycetemcomitans shows enhanced leukotoxic activity and is mostly present in individuals of [...] Read more.
Aggregatibacter actinomycetemcomitans is a key pathogen that has been associated with periodontal disease. Its most important virulence factor is a leukotoxin capable of inactivating immune cells. The JP2 genotype of Aggregatibacter actinomycetemcomitans shows enhanced leukotoxic activity and is mostly present in individuals of North and West African origin with severe periodontitis. In this paper, two cases of Caucasians diagnosed with the JP2 genotype are presented. A 50-year-old female patient had three approximal sites with ≥ 6 mm clinical attachment loss (CAL) and eight sites with probing depth (PD) ≥ 5 mm. Microbiological diagnostics revealed A. actinomycetemcomitans JP2 genotype, but not Porphyromonas gingivalis. This JP2 genotype was highly leukotoxic to monocytic cells. The second case was a 55-year-old female patient with CAL of > 5 mm at all molars and PD of up to 12 mm. A. actinomycetemcomitans JP2 was identified, but not P. gingivalis. Her husband originated from North-Africa. In him, no A. actinomycetemcomitans was detected, but their 17-year-old daughter was diagnosed with periodontitis and was found to be positive for the JP2 genotype. Both patients were successfully treated with adjunctive antibiotics and the JP2 genotype was eliminated. In summary, here, the microbiological diagnosis was key for the treatment with adjunctive antibiotics. Full article
(This article belongs to the Special Issue Aggregatibacter actinomycetemcomitans—Gram-Negative Bacterial Pathogen)
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Obituary
In Memoriam: Edward “Ned” Lally
by Nataliya Balashova
Pathogens 2020, 9(3), 177; https://doi.org/10.3390/pathogens9030177 - 01 Mar 2020
Cited by 1 | Viewed by 1205
Abstract
On February 11, 2019, we lost a colleague and friend Dr [...] Full article
(This article belongs to the Special Issue Aggregatibacter actinomycetemcomitans—Gram-Negative Bacterial Pathogen)
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