Aggregatibacter actinomycetemcomitans: virulence of its leukotoxin and association with aggressive periodontitis

Abstract

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.

Keywords: IL-1β; aggregatibacter actinomycetemcomitans; aggressive periodontitis; bone resorption; infection; inflammation; leukotoxin.

Figure 1.

Clinical presentation of localized aggressive periodontitis. A 16-year old female presenting with radiographic alveolar bone loss associated with bone defects (marked with arrows) and probing attachment loss at 2 permanent first molars, left upper premolars and lower incisors. Clinical photographs buccal view (A–C). Radiographs (D–F). The clinical presentation shows sparse plaque accumulation and localized gingival inflammation with 4–8 mm periodontal crevices with bleeding on probing in the affected regions. The results from the microbial sampling are presented in the inserted table and the sampled sites are indicated. Microbiological analysis, by cultivation technique, confirmed the presence of high levels of A. actinomycetemcomitans in the 3 lesions sampled. Diagnosis: localized aggressive periodontitis (LAgP).

Figure 2.

(A) Interaction of A. actinomycetemcomitans leukotoxin (LtxA) with T-, B-lymphocytes, polymorphonuclear (PMN) leukocytes, and macrophages leads to cell lysis. (B) LtxA-induced cell death in macrophages involves several steps before the cell lysis occurs. LtxA binds to LFA-1 (1) and induces extracellular release of ATP (2). The released ATP binds to the P2X₇-receptor (3) that subsequently causes efflux of potassium (4). The inflammasome complex is formed and activated (5), which promotes the cleavage and activation of a cysteine proteinase called caspase-1 (6). The cleaved caspase-1 is then responsible for activation (7) and release of abundant levels of active IL-1β and IL-18 (8).