However, this is not surprising, as similar heterogeneity in the selleckchem transcription regulation might exist even among different strains within the same species. Finally, CovRS has been reported to obviously respond to so far unknown molecular signals in human blood. Analysis of GAS global transcription during ex vivo culture in human whole blood revealed that CovRS is involved in GAS adaptation allowing growth in blood [13]. We observed that covS

insertional mutants in the M6, M2 and M18 background were significantly attenuated in their VX-680 in vivo efficiency to multiply in whole human blood, suggesting a high importance of the sensor kinase activity for blood survival. However, this cannot be postulated for M49 591, which is a skin isolate. Moreover, since the adaptation in human blood is associated mainly with pathogenesis during invasive growth, the involvement of CovS to the response to human blood exposure is not a uniform characteristic among different GAS serotype strains. Most recently, a paper published during the review PDGFR inhibitor process of this work by Trevino and colleagues uncovered that CovR retains some regulatory activity in the absence of a functional CovS sensor kinase and that CovS mutants are hypervirulent in ex vivo and in vivo

models of invasive infection [14]. However, CovS mutants were attenuated in their ability to survive in human saliva, which could be one possible explanation why no natural CovS mutants are transmitted from host to host [14]. Conclusion Taken together, no serotype-dependent contribution on regulation of capsule expression and adherence to human keratinocytes was observed. Interestingly, an increased capsule expression in M2, M6 and M18 CovS mutants did not lead to enhanced survival of the bacteria in whole human blood. In contrast, Liothyronine Sodium the effect of CovS on biofilm formation depended on the examined strain. This finding implies that the CovRS system has divergent

effects on similar target genes in different strains. Thus, the CovRS system could differ with respect to its repertoire of regulated genes in a strain-dependent manner. In summary, in addition to Nra, the CovRS system is the second regulator in GAS with serotype- or even strain-dependent activity, further supporting the emerging scheme of divergent regulatory circuits in GAS. Acknowledgements This research was supported by grants from the Federal Ministry of Education and Research (BMBF) – financed networks “”ERA-NET Pathogenomics”" and SysMo “”Systems Biology of Microorganisms”" awarded to B.K and A.P. (BMBF grants BE031-03U213B, 0313936A and 0313979B) The authors would like to thank Ludwig Jonas from the Electron Microscopy Unit of the University Clinic Rostock for support in obtaining REM pictures, and Jana Normann, Yvonne Humbold, Kathleen Arndt and Lars Middelborg for expert technical assistance.