THE RV2577 GENE OF Mycobacterium tuberculosis IS A VIRULENCE FACTOR IN TUBERCULOSIS PATHOGENESIS

FORRELLAD M.A.; VAZQUEZ, C.L.; BLANCO F.C.; KLEPP L.I.; BIGI F

Mar del Plata

Congreso; SAIB -51 Annual Meeting; 2015

Sociedad Argentina de Investigaciones Bioquímicas y Biología Molecular.

Mycobacterium tuberculosis is the causative agent of Tuberculosis. The outcome of the host-pathogen interaction depends on the bacterium?s virulence factors and host immune system. Our group has studied a large number of mycobacterial virulence factors among them the Rv2577 gene. This gene is up-regulated in a M. bovis hyper virulent strain and also, an Rv2577 mutant strain presented an attenuated phenotype of virulence. In this study we continue the characterization of Rv2577 gene and its relevance in virulence. For this end, we analyzed the intracellular trafficking of M. tuberculosis wild type (wt), an Rv2577 mutant and a complemented strain by confocal microscopy. We observed the mutant co-localized with the LAMP2 protein, a marker of late phagosome. The wt phenotype was completely restored in the complemented strain. An in silico analysis demonstrated Rv2577 has a Tat signal sequence, suggesting its translocation out the cell. In fact, a subcellular screening by western blot performed with a polyclonal anti-Rv2577 made in this study, shown Rv2577 is localized in the cell wall fraction. Also, Rv2577 has a metallophosphoesterase domain, suggesting a phosphatase activity, yet undetermined. The results suggest Rv2577 is involved in phagosome maturation arrest, possibly by an intimal interaction with phagosomal proteins, suggesting a relevant role in the virulence of M. tuberculosis.