title: Sulfolipid accumulation in Mycobacterium tuberculosis disrupted in the mce2 operon.
abstract: Mycobacterium tuberculosis, the causative agent of tuberculosis, has a lipid-rich cell wall that serves as an effective barrier against drugs and toxic host cell products, which may contribute to the organism's persistence in a host. M. tuberculosis contains four homologous operons called nice (mce1-4) that encode putative ABC transporters involved in lipid importation across the cell wall. Here, we analyzed the lipid composition of M. tuberculosis disrupted in the mce2 operon. High resolution mass spectrometric and thin layer chromatographic analyses of the mutant's cell wall lipid extracts showed accumulation of SL-1 and SL(1278) molecules. Radiographic quantitative analysis and densitometry revealed 2.9, 3.9 and 9.8-fold greater amount of [(35)S] SL-1 in the mce2 operon mutant compared to the wild type M. tuberculosis during the early/mid logarithmic, late logarithmic and stationary phase of growth in liquid broth, respectively. The amount of [(35)S] SL(1278) in the mutant also increased progressively over the same growth phases. The expression of the mce2 operon genes in the wild type strain progressively increased from the logarithmic to the stationary phase of bacterial growth in vitro, which inversely correlated with the proportion of radiolabel incorporation into SL-1 and SL(1278) at these phases. Since the mce2 operon is regulated in wild type M. tuberculosis, its cell wall may undergo changes in SL-1 and SL(1278) contents during a natural course of infection and this may serve as an important adaptive strategy for M. tuberculosis to maintain persistence in a host.
authors: School of Public Health, University of California, Berkeley, CA 94720, USA. omarjanovic@berkeley.edu
authors: Olivera
authors: O
authors: Marjanovic
authors: Anthony T
authors: AT
authors: Iavarone
authors: Lee W
authors: LW
authors: Riley
mesh_terms: D000942:Antigens, Bacterial / Q000235:genetics* / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D002473:Cell Wall / Q000378:metabolism; D002855:Chromatography, Thin Layer; D006801:Humans; D008055:Lipids / Q000096:biosynthesis*; D013058:Mass Spectrometry; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000378:metabolism; D009876:Operon; D014376:Tuberculosis / Q000382:microbiology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D008055:Lipids; C443482:mce2 protein, Mycobacterium tuberculosis; C015518:sulfolipids