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Mycobacterium tuberculosis protease MarP activates a peptidoglycan hydrolase during acid stress

Helene Botella1, Julien Vaubourgeix1, Myung Hee Lee2

  • 1Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY, USA.

The EMBO Journal
|January 7, 2017
PubMed

Insights

Mycobacterium tuberculosis uses the protease MarP to activate RipA, enabling survival in acidic host environments. This process is crucial for cell wall maintenance and preventing cell division defects during infection.

Area of Science:

  • Microbiology
  • Cell Biology
  • Biochemistry

Background:

  • Mycobacterium tuberculosis (Mtb) establishes lifelong infections by persisting in a latent state, enduring host immune stresses.
  • The periplasmic protease MarP is essential for Mtb survival in acidified phagosomes and infection establishment.
  • The specific targets of MarP responsible for these survival mechanisms remained unidentified.

Purpose of the Study:

  • To identify the proteolytic substrates of MarP essential for Mycobacterium tuberculosis survival under acidic stress.
  • To elucidate the mechanism by which MarP contributes to Mtb's ability to withstand host immunity.

Main Methods:

  • Biochemical assays were employed to analyze protease activity.
  • Supravital chemical probes were utilized to image nascent peptidoglycan synthesis.
  • Comparative analysis of wild-type and MarP-deficient Mtb strains under acidic conditions.

Main Results:

  • MarP was demonstrated to cleave the peptidoglycan hydrolase RipA during acid stress, activating RipA.
  • MarP-deficient Mtb cells exhibited cell elongation and chain formation due to impaired RipA processing.
  • This processing defect indicates a failure in progeny cell separation.

Conclusions:

  • RipA processing by MarP is essential for Mycobacterium tuberculosis survival in acidic environments.
  • Sustained peptidoglycan hydrolysis, regulated by MarP-RipA interaction, is critical for cell wall homeostasis and Mtb persistence.
  • This finding provides a new target for anti-tuberculosis therapies aimed at disrupting Mtb's survival mechanisms.
Keywords:
acid resistancemycobacteriapeptidoglycanprotease

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