Characterization of Rv2577 and Rv2617c genes as virulence factors of Mycobacterium tuberculosis

FORRELLAD, MARINA ANDREA; BLANCO, FEDERICO CARLOS; GARCIA, E; KLEPP, LAURA INÉS; SANTANGELO, MARÍA DE LA PAZ; BIGI, FABIANA

Canela, RS

Congreso; VII Meeting of the SLAMTB; 2014

Sociedad Latinoamericana de Tuberculosis y otras Micobacteriosis

Background and objective: Mycobacterium tuberculosis is the causative agent of Tuberculosis. Once in the host, the bacterium can be eliminated, to cause an acute infection or to produce a prolonged chronic infection. The final outcome depends on the bacterium´s virulence factors and the host immune system. Our group has studied a large number of mycobacteria virulence factors among them has been demonstrated that the Rv2577 gene is up-regulated in a M. bovis hypervirulent strain and also that Erp protein interacts with the Rv2617 . The aim of the present study is to determine whether the Rv2577 and Rv2617c genes encoding virulence factors in M. tuberculosis and to approximate their biological function. Methods: For this purpose, the wild type (wt), the Rv2577 and Rv2617c mutants and complemented strains were used to infect J774 murine macrophages in which the survival and intracellular traffic were studied. Results: Interestingly, the CFUs were increased in the mutants shared to the wt in the first hours post infection (hpi) whereas a reduction in CFUs counting was observed in the mutants at 96hpi. Furthermore, confocal microscopy studies showed that both mutants co-localized with LAMP2 protein, a marker of late phagosomes. Also, an in silico studies showed that Rv2577 has sequence similarity with purple acid phosphatases suggesting a phosphatase activity which may be involved in the modulation of host signal proteins or to provide inorganic phosphate to the bacterium. Conclusion: Together these results indicate that mutants shown an attenuated phenotype suggesting that both Rv2577 and Rv2617c proteins are virulence factors important in TB pathogenesis.