Role of the Mce1 transporter in the lipid homeostasis of Mycobacterium tuberculosis.
Tuberculosis is one of the leading causes of mortality throughout the world. Mycobacterium tuberculosis, the causative agent of human tuberculosis, has developed several strategies involving proteins and other compounds known collectively as virulence factors to subvert human host defences and invade the human host. The Mce proteins are among these virulence-related proteins and are encoded by the mce1, mce2, mce3 and mce4 operons in the genome of M. tuberculosis. It has been proposed that these operons encode ABC-like lipid transporters; however, the nature of their substrates has only been revealed in the case of the Mce4 proteins. Here we found that the knockout of the mce1 operon alters the lipid profile of M. tuberculosis H37Rv and the uptake of palmitic acid. Thin layer chromatography and liquid chromatography-mass spectrometry analysis showed that the mce1 mutant accumulates more mycolic acids than the wild type and complemented strains. Interestingly, this accumulation of mycolic acid is exacerbated when bacteria are cultured in the presence of palmitic acid or arachidonic acid. These results suggest that the mce1 operon may serve as a mycolic acid re-importer.
Instituto de Biotecnología, CICVyA - INTA, N. Repetto and De los Reseros, Hurlingham 1686, Argentina.
Marina Andrea
MA
Forrellad
Mycobacteria Research Laboratories, Department of Microbiology, Immunology & Pathology, Colorado State University, Fort Collins, CO 80523-1682, USA.
Michael
M
McNeil
Instituto de Biotecnología, CICVyA - INTA, N. Repetto and De los Reseros, Hurlingham 1686, Argentina.
María de la Paz
Mde L
Santangelo
Instituto de Biotecnología, CICVyA - INTA, N. Repetto and De los Reseros, Hurlingham 1686, Argentina.
Federico Carlos
FC
Blanco
Instituto de Biotecnología, CICVyA - INTA, N. Repetto and De los Reseros, Hurlingham 1686, Argentina.
Elizabeth
E
García
Instituto de Biotecnología, CICVyA - INTA, N. Repetto and De los Reseros, Hurlingham 1686, Argentina.
Laura Inés
LI
Klepp
Department of Microbiology, University of Alabama at Birmingham, 609 Bevill Biomedical Research Building, 845 19th Street South, Birmingham, AL 35294, USA.
Jason
J
Huff
Department of Microbiology, University of Alabama at Birmingham, 609 Bevill Biomedical Research Building, 845 19th Street South, Birmingham, AL 35294, USA.
Michael
M
Niederweis
Mycobacteria Research Laboratories, Department of Microbiology, Immunology & Pathology, Colorado State University, Fort Collins, CO 80523-1682, USA.
Mary
M
Jackson
Instituto de Biotecnología, CICVyA - INTA, N. Repetto and De los Reseros, Hurlingham 1686, Argentina. Electronic address: fbigi@cnia.inta.gov.ar.
Fabiana
F
Bigi
D000942:Antigens, Bacterial / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D006706:Homeostasis; D006801:Humans; D006867:Hydrolases / Q000235:genetics / Q000378:metabolism*; D050356:Lipid Metabolism; D008297:Male; D009171:Mycolic Acids / Q000378:metabolism*; D009876:Operon / Q000235:genetics; D017422:Sequence Analysis, DNA; D014376:Tuberculosis / Q000378:metabolism*
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D009171:Mycolic Acids; C473802:mammalian cell entry protein Mce1A, Mycobacterium tuberculosis; D006867:Hydrolases; C527647:HsaD protein, Mycobacterium tuberculosis
Lipids; Mycobacterium tuberculosis; Mycolic acid; mce operon