Mce1 operon disruption is associated with changes in the lipid profile of M. tuberculosis

Abstract

Disrupting the mce1 operon in M. tuberculosis causes a hypervirulent phenotype and a reduced ability to stimulate Th1 type immunity in mice, suggesting that the mce1 operon is associated with persistence of the bacterium. Upon investigation of lipid extracts from wild-type (wt), mutant, and complemented strains (comp), it was observed that lipids were present on the cell surface of the mutant that were not observed in the wt or comp strains (Figure 1). The accumulating lipids were characterized as the free mycolic acids by high performance mass spectrometry. The genes encoded in mce1, include one fatty acid CoA ligase, three predicted integral membrane proteins, as well as 9 proteins likely to be associated with the cytoplasmic membrane. Six proteins within the operon have homology to the MKL family of ABC transporters. Current investigations are aimed at determining if a defect in lipid transport is causing the accumulation of the lipids on the cell surface. Further investigations are underway to determine the role of the free mycolic acids during infection. MDL and JAL thank the NIH (GM47356) for funding. SC and LWR thank Ellison Medical Foundation (Senior Global ID award) for funding Figure 1.Open in figure viewerPowerPoint Total lipid extracts from M.tuberculosis: Wild-type, k/o and complemented strains. All spectra are scaled to the peak denoted with a ‘*’.