Disease relevance of clpC

• This locus displays the same genetic organization as that of the clpC/mecB locus of Bacillus subtilis [1].
• Regulation of growth inhibition at high temperature, autolysis, transformation and adherence in Streptococcus pneumoniae by clpC [2].
• Under stress conditions, the facultative intracellular pathogen Listeria monocytogenes produces a ClpC ATPase, which is a general stress protein encoded by clpC and belonging to the HSP-100/Clp family [3].

High impact information on clpC

• The purified CtsR protein of L. monocytogenes binds specifically to the clpC, clpP and clpE regulatory regions, and the extent of the CtsR binding sites was defined by DNase I footprinting [4].
• The first gene of the clpC operon of L. monocytogenes encodes a homologue of the Bacillus subtilis CtsR repressor of stress response genes [4].
• Insertional duplication mutagenesis of clpC resulted in increased tolerance to high temperature; a result in contrast to other bacterial Clp proteases [2].
• Finally, the clpC disruption resulted in decreased genetic transformation [2].
• In the clpE-clpC double mutant, however, cell division was affected, indicating that ClpE acts synergistically with ClpC in cell septation [5].

Biological context of clpC

• Tn917 insertions inactivating the entire operon, or only clpC, gave mutants highly susceptible to stress, including iron limitation, elevated temperatures and high osmolarity [1].
• Overall, our data show that while sigmaB activation occurs through a single pathway under both environmental and energy stress conditions, regulation of expression of some stress response and virulence genes in the sigmaB regulon (e.g., clpC) appears to require networks involving multiple transcriptional regulators [6].
• Culture in charcoal-treated medium, which triggers in wild-type strains the transcriptional activation of the PrfA regulon, also caused a strong downregulation of clpC [7].

Anatomical context of clpC

• A clpC insertional mutant was also restricted in its capacity to grow in bone-marrow-derived macrophages [1].
• During the early phase of infection, a clpC mutant failed to disseminate to hepatocytes in the livers of infected mice whereas the invasive capacity of a clpE mutant remained unchanged [8].
• This was confirmed by a confocal microscopy study on infected cultured hepatocyte and epithelial cell lines, showing a strong reduction of cell invasion only by the clpC mutant [8].

Associations of clpC with chemical compounds

• In one mutant the insertion was immediately upstream of the recently identified ptsHI locus, which encodes two proteins of the phosphoenolpyruvate-dependent carbohydrate uptake system, whereas in the other the insertion was immediately upstream of an operon whose most distal gene was clpC, involved in stress responses and virulence [9].

Analytical, diagnostic and therapeutic context of clpC

• Northern blot experiments showed that expression of clpC was induced in response to high temperature (40-42 degrees C) versus 37 degrees C, suggesting that ClpC is a heat shock protein [2].
• The clpC-deficient mutant formed long chains and failed to undergo lysis after treatment with penicillin or vancomycin [2].
• Electron microscopy studies did not show any morphological alterations in clpE or clpC mutants [5].

References