CtsR, a novel regulator of stress and heat shock response, controls clp and molecular chaperone gene expression in Gram‐positive bacteria

Abstract

SummaryclpP and clpC of Bacillus subtilis encode subunits of the Clp ATP-dependent protease and are required for stress survival, including growth at high temperature. They play essential roles in stationary phase adaptive responses such as the competence and sporulation developmental pathways, and belong to the so-called class III group of heat shock genes, whose mode of regulation is unknown and whose expression is induced by heat shock or general stress conditions. The product of ctsR, the first gene of the clpC operon, has now been shown to act as a repressor of both clpP and clpC, as well as clpE, which encodes a novel member of the Hsp100 Clp ATPase family. The CtsR protein was purified and shown to bind specifically to the promoter regions of all three clp genes. Random mutagenesis, DNaseI footprinting and DNA sequence deletions and comparisons were used to define a consensus CtsR recognition sequence as a directly repeated heptad upstream from the three clp genes. This target sequence was also found upstream from clp and other heat shock genes of several Gram-positive bacteria, including Listeria monocytogenes, Streptococcus salivarius, S. pneumoniae, S. pyogenes, S. thermophilus, Enterococcus faecalis, Staphylococcus aureus, Leuconostoc oenos, Lactobacillus sake, Lactococcus lactis and Clostridium acetobutylicum. CtsR homologues were also identified in several of these bacteria, indicating that heat shock regulation by CtsR is highly conserved in Gram-positive bacteria.

The SOS response of Listeria monocytogenes is involved in stress resistance and mutagenesis

“…Several classes of stress-response genes have been described in L. monocytogenes, which are activated during exposure to specific or general stresses. In particular, the class I and class III heat-shock and the SigB response have been investigated thoroughly (Derre et al, 1999;Hanawa et al, 1999;Kazmierczak et al, 2003). Recently, it has been shown that the SOS response of L. monocytogenes is activated upon mild heat exposure (van der Veen et al, 2007).…”

Role for dnaK locus in tolerance of multiple stresses in Staphylococcus aureus

“…Class II Hsps are s B dependent, and are induced by heat and other stresses (Schulz & Schumann, 1996). Class III Hsps are Clp proteases/ ATPases, and are typically under the control of the transcriptional repressor CtsR (Derre et al, 1999). The class IV Hsps are encoded by genes that are not controlled by HrcA, s B or CtsR (Helmann et al, 2001).…”

Defining the structure of the general stress regulon of Bacillus subtilis using targeted microarray analysis and random forest classification

“…For 20 of the 37 genes, additional regulation by secondary regulators has already been proven by previous studies. These 20 genes are: bioB, bmrR, purK, radA, yacK, yacM, ydaF, ykrT, yocL, ypuD, yraA, ysnF, ywhH, yxjG and the operon yceC-yceD-yceE-yceF-yceG-yceH (Au et al, 2005;Banse et al, 2008;Baranova et al, 1999;Bower et al, 1996; Cao et al, 2002;Chu et al, 2006;Chumsakul et al, 2011;Comella & Grossman, 2005;Derré et al, 1999;Drzewiecki et al, 1998;Ebbole & Zalkin, 1987;Eiamphungporn & Helmann, 2008;Erwin et al, 2005;Grundy & Henkin, 1998; Höper et al, 2005;Jervis et al, 2007;Kearns et al, 2005; Krüger et al, 1996;Kumaraswami et al, 2010;Leelakriangsak et al, 2007;Lei et al, 2009;Marvasi et al, 2010;Nakano et al, 2003;Nguyen et al, 2009;Perkins et al, 1996; Petersohn et al, 2001;Sekowska & Danchin, 2002;Wang et al, 2006;Weng et al, 1995; You et al, 2008). Details about their secondary regulators are included in Supplementary Table S4.…”