CovS/CovR of group B streptococcus: a two-component global regulatory system involved in virulence.
Lamy, Marie-Cecile 1,2,3; Zouine, Mohammed 4; Fert, Juliette 2; Vergassola, Massimo 4; Couve, Elisabeth 4; Pellegrini, Elisabeth 1; Glaser, Philippe 4; Kunst, Frank 4; Msadek, Tarek 2; Trieu-Cuot, Patrick 1,2; Poyart, Claire 1,2,3
[Article]
Molecular Microbiology.
54(5):1250-1268, December 2004.
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Summary: In this study, we carried out a detailed structural and functional analysis of a Streptococcus agalactiae (GBS) two-component system which is orthologous to the CovS/CovR (CsrS/CsrR) regulatory system of Streptococcus pyogenes. In GBS, covR and covS are part of a seven gene operon transcribed from two promoters that are not regulated by CovR. A [DELTA]covSR mutant was found to display dramatic phenotypic changes such as increased haemolytic activity and reduced CAMP activity on blood agar. Adherence of the [DELTA]covSR mutant to epithelial cells was greatly increased and analysis by transmission electron microscopy revealed the presence at its surface of a fibrous extracellular matrix that might be involved in these intercellular interactions. However, the [DELTA]covSR mutant was unable to initiate growth in RPMI and its viability in human normal serum was greatly impaired. A major finding of this phenotypic analysis was that the CovS/CovR system is important for GBS virulence, as a 3 log increase of the LD50 of the mutant strain was observed in the neonate rat sepsis model. The pleiotropic phenotype of the [DELTA]covSR mutant is in full agreement with the large number of genes controlled by CovS/CovR as seen by expression profiling analysis, many of which encode potentially secreted or cell surface-associated proteins: 76 genes are repressed whereas 63 were positively regulated. CovR was shown to bind directly to the regulatory regions of several of these genes and a consensus CovR recognition sequence was proposed using both DNase I footprinting and computational analyses.
Copyright (C) 2004 Blackwell Publishing Ltd.