Survival of an Aggregatibacter actinomycetemcomitans quorum sensing luxS mutant in the mouths of Rhesus monkeys: Insights into Ecological Adaptation

Summary

Experiments were designed to explore a prominent autoinducer-2 (AI-2) producing gene (luxS) related to colonization and survival of Aggregatibacter actinomycetemcomitans, a low abundance member of the indigenous flora, that forms a key component of the dysbiotic flora in localized aggressive periodontitis. The luxS gene was disrupted in a primate strain of A. actinomycetemcomitans prior to implantation into the oral cavity of Rhesus monkeys (Rh). The colonization efficiency of the luxS mutant (RhAa-VS4) was compared to the parental wild-type strain (RhAa3) (positive control) and a ltxA mutant (RhAa-VS2) (negative control). The in vivo results showed that the luxS mutation had minimal impact on A. actinomycetemcomitans colonization as compared to the wild-type RhAa3 strain. In vitro studies revealed that there was a significant up-regulation of attachment related aae, apiA and flp in the RhAa-VS4 strain as compared to RhAa3. Biofilm forming ability was also significantly increased in RhAa-VS4 strain compared to RhAa3, while the AI-2 signal was ablated. The addition of the AI-2 precursor dihydroxy pentanedione (DPD) allowed the RhAa-VS4 strain to achieve RhAa3 biofilm levels. This is the first primate study to test the relevance of LuxS in vivo. In vitro assessment suggests that survival of RhAa-VS4 strain was due to the production of signaling autoinducer molecules derived from other members of the flora as well as the up-regulation of genes related to attachment and biofilm formation.

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