Methyl-accepting chemotaxis like Rv3499c (Mce4A) protein in Mycobacterium tuberculosis H37Rv mediates cholesterol-dependent survival

Cholesterol, an essential cellular component in macrophages, is exploited for entry and long-term survival of Mycobacterium inside the host. Cholesterol-deficient macrophages can restrict the cholesterol-dependent entry of Mycobacterium. Rv3499c protein in Mycobacterium has high binding affinity for cholesterol. Rv3499c gene is a part of mce4 operon which is reported to act as cholesterol transport system in mycobacteria. Earlier we reported Rv3499c protein to localise on cell wall and facilitate entry of Mycobacterium inside macrophages. Here we performed fold recognition and multiple sequence alignment to find similarity with methyl-accepting chemotaxis protein (MCP). MCP allows detection of level of nutrient in the medium, which in this case is cholesterol. We showed Rv3499c protein expression is important for host cholesterol utilization by Mycobacterium for its survival. Infected female balb/c mice presented increased CFU of Rv3499c overexpressing M. tuberculosis H37Rv marked with early disease conditions and increased lung pathology. Thus, findings suggest specific domain of MCP of Rv3499c help in regulation of downstream PDIM synthesis pathways for ligand utilization by M. tuberculosis H37Rv.