Mycobacterium hominissuis causes disseminated disease in immunocompromised people such as in AIDS patients, and disease in patients suffering from chronic pulmonary conditions [3]. The bacterium preferentially

infects tissue macrophages and blood monocytes. Once inside a macrophage, the bacterium has been shown to inhibit GDC-0941 solubility dmso the acidification of the phagosome and subsequently prevent the fusion between the phagosome and lysosome [4], which are key stages of phagocytes mechanisms of killing of intracellular microorganisms [5]. Similar to Mycobacterium tuberculosis [6], Salmonella [7] and Leishmania [8], M. hominissuis interferes with the endosome maturation process which precedes phagosome-lysosome fusion. The mechanisms that M. hominissuis uses to survive within macrophages have been an active area of research. Previous reports have shown that M. hominissuis has the ability to modulate the intracellular environment, remaining accessible to internalized transferrin and limiting the proteolytic activity, maintaining cathepsin D in an immature form [9]. Other studies, for example, Malik and colleagues, have suggested inhibition of calcium signaling by another pathogenic mycobacterium (M. tuberculosis) is responsible for the prevention of phagosome-lysosome fusion [10]. Li and colleagues [11], screening of M. hominissuis transposon mutant bank for clones selleck products with attenuated in human macrophages, identified

a 2D6 mutant in which the transposon interrupted MAV_2928 a PPE gene (52% homologous to Rv1787 in M. tuberculosis). MAV_2928 is expressed primarily upon macrophage phagocytosis [11]. The 2D6 mutant was significantly attenuated in macrophages in comparison to the wild-type bacterium although both bacteria had comparable ability to enter the phagocytic cells. In addition, vacuoles containing the 2D6 mutant could not prevent the acidification and subsequent fusion with the lysosomes.

The PE, PPE, and PE-PGRS families of genes in mycobacteria are dispersed throughout the genomes of M. tuberculosis, Mycobacterium bovis, M. hominissuis and Mycobacterium paratuberculosis. It was previously assumed that M. hominissuis and M. paratuberculosis lack PE-PGRS family of learn more proteins [12], but Palmatine we have recently found PE-PGRS proteins in M. hominissuis (Li, Y and colleagues, in press). These families of proteins have been associated with virulence of mycobacteria [11, 13, 14], and some of the proteins have been identified on the bacterial surface [13]. The function of the majority of PPE proteins is unknown. Recently, work with M. tuberculosis has demonstrated that PPEs are associated with the RD1 operon and participate in the secretion of ESAT-6 and CFP-10, two proteins associated with M. tuberculosis virulence [15]. Early events during the infection are likely to influence the characteristics of the macrophage vacuole. MAV_2928 gene in M. hominissuis, homologue to M.