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ClgR contributes to pulmonary pathology but not bacterial growth in Mycobacterium tuberculosis infection

Gautam, U. S.; Kaushal, D.

2020-02-05 microbiology
10.1101/2020.02.04.934901 bioRxiv
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BackgroundThe 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]. MethodsIt 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. ResultsOur results demonstrate that despite not having a deficit in growth in either murine lungs or primary macrophages, in comparison to wild type, the{Delta} clgR mutant failed to induce pulmonary pathology. ConclusionWe propose that ClgR is required for the pathogenesis of Mtb.

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