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.
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.
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.
Infant Oral Mutilation (IOM) includes germectomy and early extraction of primary and permanent incisors and canines, primarily in the lower jaw. The aim of the present study was to examine the prevalence and impact of IOM, involving the removal of mandibular permanent incisors and/or canines, on dental occlusion and Oral Health-Related Quality of Life (OHRQoL) among Kenyan adolescents from Maasai Mara. In a cross-sectional study, 284 adolescents (14–18 yrs. of age) participated in an oral examination and an interview, using a structured questionnaire on age, gender, medical history, and IOM practice. For the analysis of the dental occlusion, participants with IOM, in terms of absence of two or more permanent teeth in the mandibular incisor and/or canine tooth segments (IOM group), were compared to participants who had all six incisors and canines present in the oral cavity (control group). OHRQoL was assessed using child perception questionnaire (CPQ11–14). The majority of the participants (61%) had been exposed to IOM, among whom 164 (95%) had absence of two mandibular central incisors. More individuals in the IOM group had maxillary overjet exceeding 5 mm than in the control group (50.9% vs. 20%, p < 0.001). Nineteen (11%) subjects in the IOM group had mesial occlusion in contrast to none in the control group (p < 0.001). The mean and median total CPQ scores and the mean and median CPQ domain scores were low in both groups with no significant differences between the groups. Approximately two-thirds of the study population presented with IOM, with the majority of them missing two mandibular permanent central incisors. Although some participants with IOM had substantial maxillary overjet and mesial occlusion, only few of them showed substantial effect on their OHRQoL.
The JP2 genotype of A. actinomycetemcomitans, serotype b has attracted much interest during the past three decades due to its close association with periodontitis in young individuals and the enhanced expression of a leukotoxin (LtxA). A typical feature of this genotype is a 530-base pair (bp) deletion in the ltxCABD promoter region controlling leukotoxin expression. In the present work, we have characterized serotype b strains with four additional promoter types. Two novel types have been recognized, that is, one with a 230-bp deletion and one with a 172-bp duplication. Moreover, a strain with a 640-bp deletion and three strains with a full-length promoter, including the type strain Y4, were included in the present study. The seven strains were characterized by multi locus sequence typing (MLST) and arbitrarily primed polymerase chain reaction (PCR) and assessed for LtxA production. MLST showed that the strains with the non-JP2-like deletions represented distinct monophyletic groups, whereas the JP2 strain, HK1651, represented a separate branch. LtxA production was high in all three strains with a promoter deletion, whereas the other four strains showed significantly lower levels. It can be concluded that the genetic characterization and determination of LtxA production of A. actinomycetemcomitans isolates from individuals with periodontitis can contribute to the identification of novel virulent genotypes of this bacterium.
Aggregatibacter actinomycetemcomitans is implicated in the etiology of periodontitis that affects adolescents. The monitoring and mapping of the geographic dissemination pattern of JP2 and non-JP2 genotypes of A. actinomycetemcomitans are of interest. In Africa, the highly leukotoxic JP2 genotype is known to be prevalent, particularly in north-west Africa. The aims of this study were to determine the prevalence of JP2 and non-JP2 genotypes and investigate the oral hygiene practices among adolescents living in Maasai Mara, Kenya. A total of 284 adolescents (mean age: 15.0 yrs; SD 1.1) were interviewed regarding their age, gender, medical history, and oral hygiene practice, and the number of teeth present was recorded. One subgingival pooled plaque sample from all the first molars of each participant was analyzed by conventional PCR. The mean number of permanent teeth present was 27.9 (SD: 2.0; range: 22–32; 95% CI: 27.7–28.1). Sixteen (5.6%) and two (0.7%) adolescents were positive for non-JP2 and JP2 genotypes, respectively. For the vast majority of the adolescents, the use of a toothbrush (99.3%) and toothpaste (80.1%), as well as some kind of toothpick (>60.2%), were part of their oral hygiene practice, with dental floss (0.4%) and/or mouth rinses (0.4%) rarely being used. We have, for the first time, identified Kenyan adolescents colonized with the JP2 genotype. The prevalence of the JP2 genotype of A. actinomycetemcomitans is low, a possible indicator that it spreading through human migration from North and West Africa to East Africa is a rare occasion.