Abstract
Aggregatibacter actinomycetemcomitans has been described as a member of the indigenous oral microbiota of humans, and is involved in the pathology of periodontitis and various non-oral infections. This bacterium selectively kills human leukocytes through expression of leukotoxin, a large pore-forming protein that belongs to the Repeat in Toxin (RTX) family. The specificity of the toxin is related to its prerequisite for a specific target cell receptor, LFA-1, which is solely expressed on leukocytes. The leukotoxin causes death of different leukocyte populations in a variety of ways. It activates a rapid release of lysosomal enzymes and MMPs from neutrophils and causes apoptosis in lymphocytes. In the monocytes/macrophages, the toxin activates caspase-1, a cysteine proteinase, which causes a proinflammatory response by the activation and secretion of IL-1β and IL-18. A specific clone (JP2) of A. actinomycetemcomitans with enhanced leukotoxin expression significantly correlates to disease onset in infected individuals. Taken together, the mechanisms by which this toxin kills leukocytes are closely related to the pathogenic mechanisms of inflammatory disorders, such as periodontitis. Therapeutic strategies targeting the cellular and molecular inflammatory host response in periodontal diseases might be a future treatment alternative.
Highlights
Aggregatibacter actinomycetemcomitans has been described as a member of the indigenous oral microbiota of humans, and is involved in the pathology of periodontitis and various non-oral infections
cytolethal distending toxin (Cdt) varies among different A. actinomycetemcomitans isolates and high leukotoxin expression has been shown to correlate with disease while the role of Cdt is still less clear [1]
The A. actinomycetemcomitans leukotoxin operon consists of four coding genes designated ltxC, ltxA, ltxB and ltxD and an upstream promoter [11]. ltxA encodes the structure of the toxin, ltxC for components required for posttranslational acylation of the toxin and ltxB and D for transport of the toxin to the bacterial outer membrane
Summary
Aggregatibacter actinomycetemcomitans is a gram-negative bacterium that is present in the oral cavity of a large proportion of the human population [1]. The prevalence of this bacterium shows great variation depending on the geographic origin, age and life style of the examined population [2,3]. Cdt’s are expressed by a number of gram-negative bacteria and cause death of the host cells by blocking their proliferation [8]. Cdt varies among different A. actinomycetemcomitans isolates and high leukotoxin expression has been shown to correlate with disease while the role of Cdt is still less clear [1]. The interaction between leukotoxin and host cells will be the focus of the present paper
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