EccA1, a component of the Mycobacterium marinum ESX-1 protein virulence factor secretion pathway, regulates mycolic acid lipid synthesis

Chem Biol. 2012 Mar 23;19(3):372-80. doi: 10.1016/j.chembiol.2012.01.008.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • Bacterial Proteins
  • Lipids
  • Mycolic Acids
  • Virulence Factors
  • Adenosine Triphosphatases