Proteins unique to intraphagosomally grownMycobacterium tuberculosis

Abstract

Pathogenic mycobacteria persist and replicate within phagosomes of host phagocytes by inhibiting phagosome maturation at an early endosome stage. The molecular basis for this behavior is not understood. To identify proteins of Mycobacterium tuberculosis unique to the intraphagosomal phase, mycobacteria were purified from phagosomes of infected murine bone marrow-derived macrophages and analyzed by high-resolution 2-DE and MS. Protein patterns of intraphagosomally grown M. tuberculosis were compared with those of broth-cultured mycobacteria. The analysis revealed 11 mycobacterial proteins exclusively detected in intraphagosomal mycobacteria. Some of these proteins are involved in metabolism and cell envelope synthesis, such as the lipid carrier protein Rv1627c, and the conserved hypothetical protein Rv1130 that shows homology to a virulence-associated protein of Legionella pneumophila. The relevance of these proteins as factors enabling intracellular survival of M. tuberculosis is being discussed.

Functional Characterization of a Vitamin B 12 -Dependent Methylmalonyl Pathway in Mycobacterium tuberculosis : Implications for Propionate Metabolism during Growth on Fatty Acids

“…Propionyl-CoA, as a precursor in several lipid biosynthetic pathways, including those for the (50). The oxidation of propionyl-CoA via the methylcitrate cycle would lead to toxic levels of 2-methylcitrate, which may account, at least in part, for the attenuated phenotypes of ICL and PrpD mutants in vivo (34,36,50), even if vitamin B 12 were available. ␤-Oxidation of odd-chain fatty acids comprising five carbons or more yields an acetyl-CoA subunit(s) in addition to propionyl-CoA.…”

“…Recently, the possibility that the methylcitrate cycle might constitute the dominant pathway for propionate metabolism in vivo was investigated (37). The two key findings that motivated this investigation were the observed upregulation of methylcitrate cycle genes in the intracellular environment and in the mouse lung (34,48) and the inability of a ⌬icl1 ⌬icl2 double mutant of M. tuberculosis Erdman to grow on propionate in vitro or establish an infection in mice (36). The unusual involvement of icl1 and icl2 in both the methylcitrate cycle (as 2-methylisocitrate lyase [MCL]) and the glyoxylate cycle (as isocitrate lyase [ICL]) (18,37) in M. tuberculosis, however, complicates any interpretation of the relative importance of these pathways to M. tuberculosis metabolism.…”

Evidence for complex interactions of stress-associated regulons in an mprAB deletion mutant of Mycobacterium tuberculosis

“…Interestingly, this cluster of genes is also upregulated in the phagosomes of infected murine macrophages, and Rv1129c and Rv1131 are active in infected mice . The function of Rv1130 is unknown, but the protein has been detected in phagosomes and may contribute to intracellular survival (Mattow et al, 2006). Rv1131 (gltA1) is predicted to encode citrate synthase, an enzyme of the TCA (Krebs) cycle (Cole et al, 1998).…”

Confronting the scientific obstacles to global control of tuberculosis

“…Laboratory studies have demonstrated that specific proteins can be upregulated in specific in vivo growth conditions, for example, within phagosomes (45). However, we know little about gene expression levels in M. tuberculosis as it is found in pulmonary cavities, inside granulomas, or even circulating in the blood of individuals with TB (46).…”