Mycobacterium tuberculosis protease MarP activates a peptidoglycan hydrolase during acid stress Academic Article uri icon

Overview

MeSH Major

  • Acids
  • Bacterial Proteins
  • Enzyme Activation
  • Gene Expression Regulation, Bacterial
  • Mycobacterium tuberculosis
  • N-Acetylmuramoyl-L-alanine Amidase
  • Peptide Hydrolases
  • Stress, Physiological

abstract

  • Mycobacterium tuberculosis (Mtb) can persist in the human host in a latent state for decades, in part because it has the ability to withstand numerous stresses imposed by host immunity. Prior studies have established the essentiality of the periplasmic protease MarP for Mtb to survive in acidified phagosomes and establish and maintain infection in mice. However, the proteolytic substrates of MarP that mediate these phenotypes were unknown. Here, we used biochemical methods coupled with supravital chemical probes that facilitate imaging of nascent peptidoglycan to demonstrate that during acid stress MarP cleaves the peptidoglycan hydrolase RipA, a process required for RipA's activation. Failure of RipA processing in MarP-deficient cells leads to cell elongation and chain formation, a hallmark of┬áprogeny cell separation arrest. Our results suggest that sustaining peptidoglycan hydrolysis, a process required for cell elongation, separation of progeny cells, and cell wall homeostasis in growing cells, may also be essential for Mtb's survival in acidic conditions.

publication date

  • January 2017

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC5437814

Digital Object Identifier (DOI)

  • 10.15252/embj.201695028

PubMed ID

  • 28057704

Additional Document Info