Marina Andrea Forrellad1, Michael McNeil2, María de la Paz Santangelo1, Federico Carlos Blanco1, Elizabeth García1, Laura Inés Klepp1, Jason Huff3, Michael Niederweis3, Mary Jackson2, Fabiana Bigi4. 1. Instituto de Biotecnología, CICVyA - INTA, N. Repetto and De los Reseros, Hurlingham 1686, Argentina. 2. Mycobacteria Research Laboratories, Department of Microbiology, Immunology & Pathology, Colorado State University, Fort Collins, CO 80523-1682, USA. 3. Department of Microbiology, University of Alabama at Birmingham, 609 Bevill Biomedical Research Building, 845 19th Street South, Birmingham, AL 35294, USA. 4. Instituto de Biotecnología, CICVyA - INTA, N. Repetto and De los Reseros, Hurlingham 1686, Argentina. Electronic address: fbigi@cnia.inta.gov.ar.
Abstract
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.
Tuberculosis is one of the leading causes of mortality throughout the world. Mycobacterium tuberculosis, the causative agent of pan class="Species">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.
Authors: S Chitale; S Ehrt; I Kawamura; T Fujimura; N Shimono; N Anand; S Lu; L Cohen-Gould; L W Riley Journal: Cell Microbiol Date: 2001-04 Impact factor: 3.715
Authors: Laura I Klepp; Marina A Forrellad; Ana V Osella; Federico C Blanco; Emma J Stella; María Verónica Bianco; María de la Paz Santangelo; Cristopher Sassetti; Mary Jackson; Angel A Cataldi; Fabiana Bigi; Héctor R Morbidoni Journal: Microbes Infect Date: 2012-02-08 Impact factor: 2.700
Authors: Nobuyuki Shimono; Lisa Morici; Nicola Casali; Sally Cantrell; Ben Sidders; Sabine Ehrt; Lee W Riley Journal: Proc Natl Acad Sci U S A Date: 2003-12-08 Impact factor: 11.205
Authors: Sally A Cantrell; Michael D Leavell; Olivera Marjanovic; Anthony T Iavarone; Julie A Leary; Lee W Riley Journal: J Microbiol Date: 2013-09-14 Impact factor: 3.422
Authors: Rainer Kalscheuer; Brian Weinrick; Usha Veeraraghavan; Gurdyal S Besra; William R Jacobs Journal: Proc Natl Acad Sci U S A Date: 2010-11-30 Impact factor: 11.205
Authors: Ryan M Wells; Christopher M Jones; Zhaoyong Xi; Alexander Speer; Olga Danilchanka; Kathryn S Doornbos; Peibei Sun; Fangming Wu; Changlin Tian; Michael Niederweis Journal: PLoS Pathog Date: 2013-01-31 Impact factor: 6.823
Authors: Ellen Foot Perkowski; Brittany K Miller; Jessica R McCann; Jonathan Tabb Sullivan; Seidu Malik; Irving Coy Allen; Virginia Godfrey; Jennifer D Hayden; Miriam Braunstein Journal: Mol Microbiol Date: 2016-02-05 Impact factor: 3.501
Authors: Adriano Queiroz; Daniel Medina-Cleghorn; Olivera Marjanovic; Daniel K Nomura; Lee W Riley Journal: Pathog Dis Date: 2015-08-28 Impact factor: 3.166
Authors: Meghan E Feltcher; Harsha P Gunawardena; Katelyn E Zulauf; Seidu Malik; Jennifer E Griffin; Christopher M Sassetti; Xian Chen; Miriam Braunstein Journal: Mol Cell Proteomics Date: 2015-03-26 Impact factor: 5.911
Authors: Quan Luo; Sebastian Hiessl; Anja Poehlein; Rolf Daniel; Alexander Steinbüchel Journal: Appl Environ Microbiol Date: 2014-04-18 Impact factor: 4.792
Authors: Xavier Carette; John Platig; David C Young; Michaela Helmel; Albert T Young; Zhe Wang; Lakshmi-Prasad Potluri; Cameron Stuver Moody; Jumei Zeng; Sladjana Prisic; Joseph N Paulson; Jan Muntel; Ashoka V R Madduri; Jorge Velarde; Jacob A Mayfield; Christopher Locher; Tiansheng Wang; John Quackenbush; Kyu Y Rhee; D Branch Moody; Hanno Steen; Robert N Husson Journal: mBio Date: 2018-03-06 Impact factor: 7.867