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bioRxiv · 10.1101/2023.01.23.525157

A universal stress protein is essential for the survival of Mycobacterium tuberculosis

Banerjee, A.·Chakraborty, M. M.·Sharma, S.·Chaturvedi, R.·Bose, A.·Biswas, P.·Singh, A.·Visweswariah, S. S.
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Abstract

Mycobacterium tuberculosis employs several signaling pathways to regulate its cellular physiology and survival within the host. Mycobacterial genomes encode multiple adenylyl cyclases and cAMP effector proteins, underscoring the diverse ways in which these bacteria utilize cAMP. We have earlier identified universal stress proteins (USP), Rv1636 and MSMEG_3811 in M. tuberculosis and M. smegmatis respectively, as abundantly expressed, novel cAMP-binding proteins. In this study, we show that these USPs may function to regulate cAMP signaling by direct sequestration of the second messenger. In slow-growing mycobacteria, concentrations of Rv1636 were equivalent to the amounts of cAMP present in the cell, and overexpression of Rv1636 in M. smegmatis increased levels of bound cAMP. Rv1636 is secreted via the SecA2 secretion system in M. tuberculosis but is not directly responsible for the efflux of cAMP from the cell. While msmeg_3811 could be readily deleted from the genome of M. smegmatis, we find that the rv1636 gene is essential for growth of M. tuberculosis, and this functionality depends on the cAMP-binding ability of Rv1636. This is the first evidence of a sink for any second messenger in bacterial signaling that would allow mycobacterial cells to regulate the available intracellular free pool of cAMP.

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Banerjee, A., Chakraborty, M. M., Sharma, S., Chaturvedi, R., Bose, A., Biswas, P., Singh, A., Visweswariah, S. S.. 2023-01-23. A universal stress protein is essential for the survival of Mycobacterium tuberculosis. https://doi.org/10.1101/2023.01.23.525157

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