Rv3787c Influences Growth Dynamics of Mycobacterium tuberculosis

Rv3787c is a putative S-adenosylmethionine (SAM)-dependent methyltransferase from Mycobacterium tuberculosis, the main agent of human tuberculosis. Researchers identified a conserved non-synonymous polymorphism within the highly transmissible Latin American-Mediterranean lineage, suggesting that Rv3787c may play a role in host-pathogen interactions. In this study, we phenotypically characterized an M. tuberculosis H37Rv mutant lacking Rv3787c and evaluated the complementation of this mutant with strains carrying either the wild-type or mutant alleles of Rv3787c. The mutant strain showed no significant growth impairment under stress conditions induced by SDS or hydrogen peroxide, and it exhibited phthiocerol dimycocerosate (PDIM) and mycolic acid profiles comparable to those of the wild-type strain. Interestingly, following prolonged hypoxia and subsequent re-exposure to aerated conditions, the mutant resumed exponential growth significantly earlier than both the wild-type and complemented strains. In a human macrophage infection model, the mutant maintained persistence levels comparable to those of the wild-type and complemented strains; however, colonies were visible earlier in macrophages infected with the mutant strain. These findings suggest that while Rv3787c is not essential for intracellular survival or replication, it may influence the growth dynamics of M. tuberculosis under specific stress conditions.