5 years ago

RocA is an accessory protein to the virulence-regulating CovR/S two-component system in the group A Streptococcus.

Danger JL, Sumby P, Miller EW, Jain I, Pflughoeft KJ
Regulating gene expression during infection is critical to the ability of pathogens to circumvent the immune response and cause disease. This is true for the group A Streptococcus (GAS), a pathogen that causes both invasive (e.g. necrotizing fasciitis) and non-invasive (e.g. pharyngitis) diseases. The control of virulence (CovR/S) two-component system has a major role in regulating GAS virulence factor expression. The regulator of cov (RocA) protein, which is a predicted kinase, functions in an undetermined manner through CovR/S to alter gene expression and reduce invasive disease virulence. Here, we show that the ectopic expression of a truncated RocA derivative, harboring the membrane-spanning domains but not the dimerization or HATPase domains, is sufficient to complement a rocA mutant strain. Coupled with a previous bioinformatic study, the data are consistent with RocA being a pseudokinase. RocA reduces the ability of serotype M1 GAS isolates to express capsule and enhances their ability to evade killing in human blood, phenotypes that are not observed for M3 or M18 GAS due to isolates of these serotypes naturally harboring mutant rocA alleles. In addition, we identified that varying RocA concentration attenuates the regulatory activity of Mg2+ and the antimicrobial peptide LL-37, which positively and negatively regulate CovS function, respectively. Thus, we propose that RocA is an accessory protein to the CovR/S system that influences the ability of GAS to modulate gene expression in response to host factors. A model of how RocA interacts with CovR/S, and of the regulatory consequences of such activity, is presented.

Publisher URL: https://www.ncbi.nlm.nih.gov/pubmed/28808155

DOI: PubMed:28808155

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