ClgR contributes to pulmonary pathology but not bacterial growth inMycobacterium tuberculosisinfection

Background The Clp proteases regulator, ClgR, is encoded in the Mycobacterium tuberculosis (Mtb) genome by Rv2745c gene (clgR). ClgR is required to clear damaged proteins, thereby preventing their accumulation in the cell. It also controls the availability of key enzymes or regulators via conditional degradation mechanism of proteolytic activity in Mtb [1,2]. Methods It has been previously reported that Mtb clgR gene is induced in a sigma factor SigH-dependent manner and a deletion mutant of clgR is susceptible to growth in a hypoxic environment. Whether hypoxia is indeed a restriction factor and ClgR is required for Mtb growth in that environment remains unelucidated. We began to address this hypothesis in the C57/BL6 mouse model of TB where Mtb infected lungs do not form granuloma and the lung environment is considerably non-hypoxic. Results Our results demonstrate that despite not having a deficit in growth in either murine lungs or primary macrophages, in comparison to wild type, the ΔclgR mutant failed to induce pulmonary pathology. Conclusion We propose that ClgR is required for the pathogenesis of Mtb.