**4. Hsps and virulence in pathogenic microorganisms**

Hsps play a central role in managing the damaged or aggregated proteins inside the cells. They have been linked to the virulence of several pathogenic microbes. *Candida albicans* expresses a bonafide heat shock response that is regulated by the evolutionarily conserved, essential heat shock transcription factor Hsf1. Hsf1 is thought to play a fundamental role in thermal homeostasis, adjusting the levels of essential chaperones to changes in growth temperature (Brown et al., 2010). In *Plasmodium falciparum* heat shock protein 70 is thought to play an essential role in parasite survival and virulence inside the host; Hsp70 is also being tried as a target for designing potential anti-malarial drugs (Cockburn et al., 2010). *Histoplasma capsulatum* is the causative agent of histoplasmosis in humans. A 62 kDa Hsp (Hsp60) of *H. capsulatum* is an immunodominant antigen which has been shown to play an important role in the adaptation of the fungus to temperature stress (Guimaraes et al., 2010). *Staphylococcus aureus* and *Staphylococcus epidermidis* can cause serious chronic infections in humans. An important factor involved in the pathogenesis of *S. aureus* is its ability to be internalized by phagocytes thereby evading the host immune system. Heat shock cognate protein, Hsc70 was identified as playing an important role in the internalization mechanism of *S. aureus* (Hirschhausen et al., 2010). ClpB gene from *Enterococcus faecalis* is linked to thermotolerance and virulence of the bacteria (de Oliveira et al., 2010). The Clp proteases appear to be critical for cell development in *Caulobacter crescentu*, and stress induction in *Bacillus subtilis* (Gerth et al., 2004)*.* ClpC has been linked to the tight regulation of virulence genes in *Listeria monocytogenes*; it has been shown to be required for adhesion and invasion of the pathogen (Nair et al., 2000). ClpC has also been shown to be important for the virulence and survival of *L. monocytogenes* in macrophages (Rouquette et al., 1998). In *Salmonella typhimurium* the Clp protease, ClpP is involved in maintaining the level of Sigma factors inside the bacterium; disruption of ClpP leads to decreased virulence in mice (Webb et al., 1999). ClpP mutation significantly attenuated the virulence of *Streptococcus pneumoniae*  in murine intraperitoneal infection model (Kwon et al., 2003). Disruption of the genes for ClpXP protease in *Salmonella enterica* serovar typhimurium results in loss of virulence in mice; these mutants were more sensitive to the intracellular environment of the macrophage (Gahan & Hill, 1999).
