Analysis of the roles of the transchptional regulators VicRK and CovR in the susceptibility of Streptococcus mutans and Streptococcus sanguinis to opsonization by the complement system

Abstract

Streptococcus mutans (SM) e Streptococcus sanguinis (SS) are common bacterial species of the human oral microbiota, which are involved in the pathogenesis of dental caries. The teeth surfaces are the major ecological niches of these species. While SM are considered the major pathogens of dental caries, SS are classically defined as a beneficial commensal species, because of its ability to inhibit the establishment of SM in dental biofilms. However, both species are opportunistic pathogens of bacterial endocarditis resulted from bacteremias from oral origin. To be transmitted and to occupy their ecological niches, these microorganisms need to persist in saliva and to physiologically adapt to the biophysical conditions of their host sites. This complex process involves changes in bacterial transcriptomes in response to environmental stimuli, which include host defense factors. Transcriptomic adaptations in response to environmental stimuli are controlled by two-component systems (TCS) in bactéria. A typical TCS is composed by a membrane histidine kinase (HK) and an intracellular response regulator protein (RR). SM has the TCS designated VicRK (vic of Virulence control) and the orphan RR CovR (cov of control of virulence), which are conserved among pathogenic species of Streptococcus. In Streptococcus pneumoniae and Streptococcus pyogenes, VicRK and CovR regulate genes involved in bacterial evasion of host immune factors, a function that seems to also occur in SM. Recently, we also identified VicRK and CovR in SS. This project aims to investigate the roles of VicRK and CovR in the evasion of SM and SS to human immune factors. To that purpose, vicRK and covR mutants obtained in S. mutans UA159 and in S. sanguinis SK36 will be characterized regarding complement fixation and phagocytosis by PMN in presence of human blood. (AU)