Virulence and Pathogenicity Properties of Aggregatibacter actinomycetemcomitans

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 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.

Keywords: Aggregatibacter actinomycetemcomitans; biofilm; cytokine binding factors; cytolethal distending toxin; horizontal gene transfer; leukotoxin; lipopolysaccharides; outer membrane vesicles; proteomic.

Figure 1

Subgingival biofilm samples from pathological periodontal pockets cultivated on blood agar plates for 48 h at 37 °C in an anaerobic atmosphere. (A) Sample obtained from a periodontal pocket of a middle-aged patient diagnosed with generalized chronic periodontitis. The macroscopical observation of the plated sample showed occurrence of a variety of colonies corresponding to different bacterial species. (B) Sample obtained from a periodontal pocket of a 25-year-old patient diagnosed with localized aggressive periodontitis. The macroscopical observation of the plated sample showed predominantly the occurrence a single colony type. (C) Microscopical (50× magnification) examination indicated that all colonies belonged to the A. actinomycetemcomitans species, which was confirmed in assays based on genetic characterization.

Figure 2

Leukotoxin (LtxA) induces a rapid inflammatory cell death in human macrophages. Briefly, LtxA binds to the LFA-1 receptor (1) and induces an extracellular release of ATP (2), which act as a ligand for the P2X7-receptor and result in an efflux of potassium (3). These processes promote the formation of an inflammasome multimer (4) that activates the cysteine proteinase caspase-1, resulting in a rapid activation (5) and secretion of IL-1β (6). Courtesy of Haubek and Johansson [20].

Figure 3

Schematic representation of a putative structure of the lipid A and the core oligosaccharides of A. actinomycetemcomitans lipopolysaccharide (LPS). The lipid A (black) of A. actinomycetemcomitans LPS is formed by four primary fatty acyl chains (myristic or 3-hydroxymyristic acid) linked by ester and amide linkages to a disaccharide of glucosamine. Two of the primary fatty acyl chains are esterified by secondary fatty acids. The acylation pattern of lipid A is asymmetric with four fatty acyl chains on the non-reducing glucosamine and two on the reducing glucosamine. The inner core (purple) is linked to lipid A by a ketosidic bond and is formed by 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo) together with heptose residues such as glycero-manno-heptose. The outer core (green) usually consists of hexoses such as glucose and galactose. Functional groups such as hydroxyl and phosphate groups are common substituents in the lipid A and the core oligosaccharides. The O-specific polysaccharide chain (O-antigen) is the most variable portion in the LPS. The O-antigen consists of a large variety of sugar residues in many combinations and glycosidic linkages. For simplicity, substituents such as hydroxyl and phosphate groups (other than those in lipid A), conformational details of the monosaccharide residues, and the stereochemistry of the glycosidic bonds are not presented.