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Molecular Oral Microbiology Jun 2020Aggregatibacter actinomycetemcomitans is a Gram-negative bacterium associated with localized aggressive periodontitis, as well as other systemic diseases. This organism... (Review)
Review
Aggregatibacter actinomycetemcomitans is a Gram-negative bacterium associated with localized aggressive periodontitis, as well as other systemic diseases. This organism produces a number of virulence factors, all of which provide some advantage to the bacterium. Several studies have demonstrated that clinical isolates from diseased patients, particularly those of African descent, frequently belong to specific clones of A. actinomycetemcomitans that produce significantly higher amounts of a protein exotoxin belonging to the repeats-in-toxin (RTX) family, leukotoxin (LtxA), whereas isolates from healthy patients harbor minimally leukotoxic strains. This finding suggests that LtxA might play a key role in A. actinomycetemcomitans pathogenicity. Because of this correlation, much work over the past 30 years has been focused on understanding the mechanisms by which LtxA interacts with and kills host cells. In this article, we review those findings, highlight the remaining open questions, and demonstrate how knowledge of these mechanisms, particularly the toxin's interactions with lymphocyte function-associated antigen-1 (LFA-1) and cholesterol, enables the design of targeted anti-LtxA strategies to prevent/treat disease.
Topics: Aggregatibacter actinomycetemcomitans; Exotoxins; Humans; Lymphocyte Function-Associated Antigen-1; Virulence Factors
PubMed: 32061022
DOI: 10.1111/omi.12284 -
Frontiers in Immunology 2019is a low-abundance Gram-negative oral pathobiont that is highly associated with a silent but aggressive orphan disease that results in periodontitis and tooth loss in... (Review)
Review
is a low-abundance Gram-negative oral pathobiont that is highly associated with a silent but aggressive orphan disease that results in periodontitis and tooth loss in adolescents of African heritage. For the most part conducts its business by utilizing strategies allowing it to conceal itself below the radar of the host mucosal immune defense system. A great deal of misinformation has been conveyed with respect to biology in health and disease. The purpose of this review is to present misconceptions about and the strategies that it uses to colonize, survive, and evade the host. In the process manages to undermine host mucosal defenses and contribute to disease initiation. This review will present clinical observational, molecular, and interventional studies that illustrate genetic, phenotypic, and biogeographical tactics that have been recently clarified and demonstrate how survives and suppresses host mucosal defenses to take part in disease pathogenesis. At one point in time was considered to be the causative agent of Localized Aggressive Periodontitis. Currently, it is most accurate to look at as a community activist and necessary partner of a pathogenic consortium that suppresses the initial host response so as to encourage overgrowth of its partners. The data for activist role stems from molecular genetic studies complemented by experimental animal investigations that demonstrate how establishes a habitat (housing), nutritional sustenance in that habitat (food), and biogeographical mobilization and/or relocation from its initial habitat (transportation). In this manner can transfer to a protected but vulnerable domain (pocket or sulcus) where its community activism is most useful. 's "strategy" includes obtaining housing, food, and transportation at no cost to its partners challenging the economic theory that "there ain't no such thing as a free lunch." This "strategy" illustrates how co-evolution can promote survival, on one hand, and overgrowth of community members, on the other, which can result in local host dysbiosis and susceptibility to infection.
Topics: Adolescent; Aggregatibacter actinomycetemcomitans; Aggressive Periodontitis; Animals; Biofilms; Genes, Bacterial; Host Microbial Interactions; Humans; Immunity, Mucosal; Models, Immunological; Pasteurellaceae Infections
PubMed: 31040843
DOI: 10.3389/fimmu.2019.00728 -
Archives of Oral Biology Aug 2020This 6-year study evaluatedAggregatibacter actinomycetemcomitans outcomes and their relationship to clinical status. (Review)
Review
OBJECTIVE
This 6-year study evaluatedAggregatibacter actinomycetemcomitans outcomes and their relationship to clinical status.
DESIGN
From the eligible individuals (23-70 years of age), 31 regular compliers (between-visit interval < 6 months) were randomly selected and matched for age/sex with 31 irregular compliers (between-visit interval > 6 months). Periodontal clinical examination and subgingival samples were obtained 5 times: T1 (baseline), T2 (after active periodontal therapy), T3 (2 years), T4 (4 years), and T5 (6 years). Total bacteria load, A. actinomycetemcomitans, and red complex species Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola levels were determined by qPCR while PCR was used to determine the occurrence of the a-b-c-d-e-f-g serotypes and the JP2 clone of A. actinomycetemcomitans. Data between groups was compared over time.
RESULTS
At baseline PCR revealed A. actinomycetemcomitans prevalence of 9.7 % and JP2 prevalence of 6.7 %. A. actinomycetemcomitans qPCR levels were higher among individuals < 35 years of age and increased at T2 in irregular compliers. At in irregular compliers at the three follow-up visits. Serotypes a, d, and f showed greater values in at least one follow-up visit in regular compliers. A. actinomycetemcomitans showed negative correlation with probing depth (PD) while serotype b showed negative correlations with PD, PI, clinical attachment level and red complex.
CONCLUSIONS
Longitudinally, compliance during PMT contributed to lower A. actinomycetemcomitans levels with some degree of correlation with clinical status. However, this study failed to report any positive effect on the occurrence of the most virulent representatives, i.e. serotype b and the JP2 clone.
Topics: Adult; Aged; Aggregatibacter actinomycetemcomitans; Humans; Middle Aged; Pasteurellaceae Infections; Periodontics; Porphyromonas gingivalis; Serogroup; Tannerella forsythia; Treponema denticola; Young Adult
PubMed: 32422332
DOI: 10.1016/j.archoralbio.2020.104747 -
Journal of Dental Research Jun 2010Aggregatibacter actinomycetemcomitans is a Gram-negative bacterium that colonizes the human oral cavity and is the causative agent for localized aggressive periodontitis... (Review)
Review
Aggregatibacter actinomycetemcomitans is a Gram-negative bacterium that colonizes the human oral cavity and is the causative agent for localized aggressive periodontitis (LAP), an aggressive form of periodontal disease that occurs in adolescents. A. actinomycetemcomitans secretes a protein toxin, leukotoxin (LtxA), which helps the bacterium evade the host immune response during infection. LtxA is a membrane-active toxin that specifically targets white blood cells (WBCs). In this review, we discuss recent developments in this field, including the identification and characterization of genes and proteins involved in secretion, regulation of LtxA, biosynthesis, newly described activities of LtxA, and how LtxA may be used as a therapy for the treatment of diseases.
Topics: Actinobacillus Infections; Adolescent; Aggregatibacter actinomycetemcomitans; Aggressive Periodontitis; Bacterial Toxins; Cytotoxins; Exotoxins; Humans; Immunosuppressive Agents; Leukocytes
PubMed: 20200418
DOI: 10.1177/0022034510363682 -
Medicina Clinica Oct 2021
Topics: Aggregatibacter aphrophilus; Anti-Bacterial Agents; Brain Abscess; Humans
PubMed: 33277020
DOI: 10.1016/j.medcli.2020.07.049 -
Frontiers in Cellular and Infection... 2023Cytolethal distending toxins (Cdt) are a family of toxins produced by several human pathogens which infect mucocutaneous tissue and induce inflammatory disease. Human...
Cytolethal distending toxins (Cdt) are a family of toxins produced by several human pathogens which infect mucocutaneous tissue and induce inflammatory disease. Human macrophages exposed to () Cdt respond through canonical and non-canonical inflammasome activation to stimulate cytokine release. The inflammatory response is dependent on PI3K signaling blockade via the toxin's phosphatidylinositol-3,4,5-triphosphate (PIP3) phosphatase activity; converting PIP3 to phosphatidylinsoitol-3,4-diphosphate (PI3,4P2) thereby depleting PIP3 pools. Phosphoinositides, also play a critical role in phagosome trafficking, serving as binding domains for effector proteins during phagosome maturation and subsequent fusion with lysosomes. We now demonstrate that Cdt manipulates the phosphoinositide (PI) pools of phagosome membranes and alters Rab5 association. Exposure of macrophages to Cdt slowed phagosome maturation and decreased phago-lysosome formation, thereby compromising macrophage phagocytic function. Moreover, macrophages exposed to Cdt showed decreased bactericidal capacity leading to increase in survival. Thus, Cdt may contribute to increased susceptibility to bacterial infection. These studies uncover an underexplored aspect of Cdt function and provide new insight into the virulence potential of Cdt in mediating the pathogenesis of disease caused by Cdt-producing organisms such as
Topics: Humans; Aggregatibacter actinomycetemcomitans; Phosphatidylinositol 3-Kinases; Phagocytes; Macrophages; Phosphatidylinositols
PubMed: 37719670
DOI: 10.3389/fcimb.2023.1220089 -
Molecular Oral Microbiology Jun 2016Aggregatibacter actinomycetemcomitans is a perio-pathogenic bacteria that has long been associated with localized aggressive periodontitis. The mechanisms of its... (Review)
Review
Aggregatibacter actinomycetemcomitans is a perio-pathogenic bacteria that has long been associated with localized aggressive periodontitis. The mechanisms of its pathogenicity have been studied in humans and preclinical experimental models. Although different serotypes of A. actinomycetemcomitans have differential virulence factor expression, A. actinomycetemcomitans cytolethal distending toxin (CDT), leukotoxin, and lipopolysaccharide (LPS) have been most extensively studied in the context of modulating the host immune response. Following colonization and attachment in the oral cavity, A. actinomycetemcomitans employs CDT, leukotoxin, and LPS to evade host innate defense mechanisms and drive a pathophysiologic inflammatory response. This supra-physiologic immune response state perturbs normal periodontal tissue remodeling/turnover and ultimately has catabolic effects on periodontal tissue homeostasis. In this review, we have divided the host response into two systems: non-hematopoietic and hematopoietic. Non-hematopoietic barriers include epithelium and fibroblasts that initiate the innate immune host response. The hematopoietic system contains lymphoid and myeloid-derived cell lineages that are responsible for expanding the immune response and driving the pathophysiologic inflammatory state in the local periodontal microenvironment. Effector systems and signaling transduction pathways activated and utilized in response to A. actinomycetemcomitans will be discussed to further delineate immune cell mechanisms during A. actinomycetemcomitans infection. Finally, we will discuss the osteo-immunomodulatory effects induced by A. actinomycetemcomitans and dissect the catabolic disruption of balanced osteoclast-osteoblast-mediated bone remodeling, which subsequently leads to net alveolar bone loss.
Topics: Aggregatibacter actinomycetemcomitans; Aggressive Periodontitis; Alveolar Bone Loss; Homeostasis; Host-Pathogen Interactions; Humans; Immunity, Innate; Inflammasomes; Pasteurellaceae Infections; Signal Transduction; Virulence Factors
PubMed: 26197893
DOI: 10.1111/omi.12119 -
Virulence 2015Periodontitis is an infection-induced inflammatory disease that causes loss of the tooth supporting tissues. Much focus has been put on comparison of the microbial... (Review)
Review
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.
Topics: Adolescent; Aggregatibacter actinomycetemcomitans; Aggressive Periodontitis; Bone Resorption; Exotoxins; Female; Genetic Variation; Humans; Interleukin-1beta; Virulence Factors
PubMed: 25494963
DOI: 10.4161/21505594.2014.982428 -
Journal of Medical Microbiology Dec 2022are Gram-negative, facultatively anaerobic rods or coccobacilli that are infrequently encountered as pathogens causing infection. The range of invasive infection that...
are Gram-negative, facultatively anaerobic rods or coccobacilli that are infrequently encountered as pathogens causing infection. The range of invasive infection that cause is poorly described. The pathogenicity of species such as is debated. To identify invasive infection due to species in a large healthcare organization and to characterize clinical syndromes, co-morbidities and risk factors. All microbiological samples positive for species were identified by conventional culture or 16S rRNA PCR between October 2017 and March 2021. Electronic records for all patients with positive samples were reviewed and the infection syndrome classified for patients with invasive disease. Twenty-seven patients with invasive infection were identified, with a statistically significant difference in species-specific patterns of invasive infection (=0.02) and a statistically significant association with residence in the 30 % most deprived households in the UK by postcode (<0.01). The three most common co-morbidities were periodontitis or recent dental work (29.6%), cardiovascular disease (25.9%) and diabetes (18.5 %). We describe a novel association of with skin and soft tissue infection. The propensity of the species to cause invasive infection at different body sites and be associated with deprivation is reported. bacteraemia was associated with infective endocarditis, and was implicated in severe appendicitis and noted to cause brain abscess. Areas warranting future research include exploring the risk-factors required for invasive infection and those that may determine the species-specific differences in patterns of invasive disease.
Topics: Humans; Aggregatibacter; Retrospective Studies; RNA, Ribosomal, 16S; Endocarditis, Bacterial
PubMed: 36748613
DOI: 10.1099/jmm.0.001612 -
The Pediatric Infectious Disease Journal Jan 2015Aggregatibacter actinomycemcomitans, previously named Actinobacillus actinomycetemcomitans (Aa), is a facultative Gram-negative slow-growing coccobacillus associated... (Review)
Review
Aggregatibacter actinomycemcomitans, previously named Actinobacillus actinomycetemcomitans (Aa), is a facultative Gram-negative slow-growing coccobacillus associated with severe oral and nonoral infections. It is a member of the HACEK group. Pulmonary infection caused by Aa is rare. We describe two cases of Aa pneumonia mimicking malignancy and review published pediatric cases.
Topics: Adolescent; Aggregatibacter; Child; Diagnosis, Differential; Humans; Lung Neoplasms; Male; Pasteurellaceae Infections; Pneumonia, Bacterial
PubMed: 25068288
DOI: 10.1097/INF.0000000000000493