Document Detail


EccA1, a Component of the Mycobacterium marinum ESX-1 Protein Virulence Factor Secretion Pathway, Regulates Mycolic Acid Lipid Synthesis.
MedLine Citation:
PMID:  22444592     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Pathogenic mycobacteria, which cause multiple diseases including tuberculosis, secrete factors essential for disease via the ESX-1 protein export system and are partially protected from host defenses by their lipid-rich cell envelopes. These pathogenic features of mycobacterial biology are believed to act independently of each other. Key ESX-1 components include three ATPases, and EccA1 (Mycobacterium marinum MMAR_5443; M. tuberculosis Rv3868) is the least characterized. Here we show that M. marinum EccA1's ATPase activity is required for ESX-1-mediated protein secretion, and surprisingly for the optimal synthesis of mycolic acids, integral cell-envelope lipids. Increased mycolic acid synthesis defects, observed when an EccA1-ATPase mutant is expressed in an eccA1-null strain, correlate with decreased in vivo virulence and intracellular growth. These data suggest that two mycobacterial virulence hallmarks, ESX-1-dependent protein secretion and mycolic acid synthesis, are critically linked via EccA1.
Authors:
Shilpa A Joshi; David A Ball; Mei G Sun; Fredric Carlsson; Brigitte Y Watkins; Nina Aggarwal; Jenna M McCracken; Kassidy K Huynh; Eric J Brown
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Chemistry & biology     Volume:  19     ISSN:  1879-1301     ISO Abbreviation:  Chem. Biol.     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-03-26     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9500160     Medline TA:  Chem Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  372-80     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Ltd. All rights reserved.
Affiliation:
Department of Microbial Pathogenesis, Genentech, South San Francisco, CA 94080, USA.
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