Host-Pathogen Interactions in Streptococcal Diseases by G. Singh Chhatwal

Author:G. Singh Chhatwal
Language: eng
Format: epub
Publisher: Springer Berlin Heidelberg, Berlin, Heidelberg

3 Streptococcal Two-Component Signal Transduction Systems

3.1 The CovRS/CsrRSS system

The CovRS/CsrRS TCS is the best characterized in S. pyogenes and S. agalactiae. In S. pyogenes, it was first discovered by several groups as a major regulator of capsule gene expression, streptolysin S production, and cysteine protease SpeB expression (Levin and Wessels 1998; Heath et al. 1999; Bernish and van de Rijn 1999). This system is functionally connected to S. pyogenes general stress response, including growth in heat, acid environments, and under salt stress. CovRS is also important for growth under iron starvation, in the presence of antimicrobial peptides, and plays a role in the serotype-dependent S. pyogenes biofilm formation and keratinocyte adherence (Dalton et al. 2006; Froehlich et al. 2009; Sugareva et al. 2010). Moreover, it is apparently the major sensor of S. pyogenes for Mg2+ (Gryllos et al. 2007).

Apart from the above-mentioned S. pyogenes virulence factors and functions, many more are directly or indirectly under control of this important TCS. A total of 15 % of all genes encoded on the S. pyogenes chromosome are repressed by CovR, including its own gene. The activity of CovR on most promoters is direct and involves the consensus binding sequence ATTARA, mutation of which relieved CovR repression. Promoter occlusion is the primary mechanism of repression by CovR (Gusa and Scott 2005). Phosphorylation of CovR is critical to its functional activity and leads to dimerization (Gao et al. 2005; Gusa et al. 2006). However, a subcutaneous mouse infection model revealed that CovR is independent of its cognate sensor kinase CovS to get phosphorylated and exert its control functions, suggesting other sources for phosphotransfer (Dalton et al. 2006). Eukaryotic-type serine/threonine kinases, discussed in the next section, are donors for phosphotransfer. Of note, the HK CovS itself was found to inactivate the RR CovR, thereby allowing S. pyogenes to grow under the above-mentioned stress conditions. Thus, the CovRS system has a Janus-like behavior. CovS acts as a kinase to activate the CovR response regulator, which subsequently acts as gene repressor. However, CovS, upon environmental stimulation, can act as a phosphatase inactivating CovR to permit gene transcription from respective promoters. The importance, functional activity and the Janus-like behavior of this system in S. pyogenes have recently been reviewed (Churchward 2007).

Although CovRS is among the most important TCS in S. pyogenes, it is not a master regulator per se, but is rather integrated into existing regulatory networks and is connected and linked to other S. pyogenes stand-alone regulators and sRNAs (Kreikemeyer et al. 2003; Fiedler et al. 2010a). Roberts and Scott investigated the link between CovRS and the Mga regulon (described elsewhere in this review) and found CovRS to repress RivR, a RALP-family regulator (Ralp4). Adjacent to rivR these authors identified rivX, encoding a small regulatory RNA. RivR enhanced transcription by Mga in vivo and in vitro and the rivRX locus was involved in pathogenesis in a mouse soft tissue infection model (Roberts and Scott 2007). Another S. pyogenes TCS, termed TrxSR, which is homologous to the S. pneumoniae HK07/RR07 system, was found as another CovR repressed system (Leday et al.

Download

Copyright Disclaimer:
This site does not store any files on its server. We only index and link to content provided by other sites. Please contact the content providers to delete copyright contents if any and email us, we'll remove relevant links or contents immediately.