Article

The Two-Domain LysX Protein of Mycobacterium tuberculosis Is Required for Production of Lysinylated Phosphatidylglycerol and Resistance to Cationic Antimicrobial Peptides

Department of Biochemistry, The University of Texas Health Center at Tyler, Tyler, TX, USA.
PLoS Pathogens (Impact Factor: 8.06). 08/2009; 5(7):e1000534. DOI: 10.1371/journal.ppat.1000534
Source: PubMed

ABSTRACT Author Summary
The human pathogen Mycobacterium tuberculosis (Mtb) survives in the hostile intracellular environment, in part, by withstanding the actions of host-induced cationic antimicrobial peptides (CAMPs). Membrane phospholipid composition and the resultant charge could play an important role in Mtb survival within the host. Acidic phospholipids such as cardiolipin, phosphatidylinositol and its mannoside derivatives, phosphatidylglycerol, and a single basic species, phosphatidylethanolamine, are constituents of the Mtb membrane bilayer. We demonstrate that lysinylated phosphatidylglycerol (L-PG) represents another basic phospholipid and that the lysX gene, which encodes a two-domain protein with lysyl transferase and lysyl-tRNA synthase activities, is necessary for L-PG production. We show that L-PG is required for maintenance of an optimal membrane potential and resistance towards CAMPs. Phagosomes containing the lysX mutant showed an increased association with lysosomes, and the lysX mutant showed growth defects in mouse and guinea pig lungs, indicating that LysX activity is required for full virulence. Collectively, our results suggest that LysX activity, which is responsible for the production of L-PG, is necessary for maintenance of an optimal membrane potential such that the pathogen can grow optimally upon infection, presumably by withstanding the actions of CAMPs.

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Available from: Murty V Madiraju, Jul 06, 2015
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