EccA1, a Component of the Mycobacterium marinum ESX-1 Protein Virulence Factor Secretion Pathway, Regulates Mycolic Acid Lipid Synthesis

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...

Full description

Saved in:
Bibliographic Details
Published in:Chemistry & biology 2012-03, Vol.19 (3), p.372-380
Main Authors: Joshi, Shilpa A., Ball, David A., Sun, Mei G., Carlsson, Fredric, Watkins, Brigitte Y., Aggarwal, Nina, McCracken, Jenna M., Huynh, Kassidy K., Brown, Eric J.
Format: Article
Language:English
Subjects:
Adenosine Triphosphatases - genetics
Adenosine Triphosphatases - metabolism
Animals
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Lipids - biosynthesis
Models, Molecular
Mycobacterium marinum - enzymology
Mycobacterium marinum - metabolism
Mycolic Acids - metabolism
Secretory Pathway
Virulence Factors - metabolism
Zebrafish
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. ► ESX-1 protein export and full mycolate production require EccA1 ATPase function ► EccA1 and lipid synthases important for virulence copurify from the cytosol ► ATPase mutant EccA1 expression sensitizes cells to mycolic acid synthesis stress ► Mycolate synthesis defects may support decreased in vivo virulence and growth
ISSN:1074-5521
1879-1301
DOI:10.1016/j.chembiol.2012.01.008