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Mycoplasma pneumoniae CARDS toxin exploits host cell endosomal acidic pH and vacuolar ATPase proton pump to execute

Kumaraguruparan Ramasamy1, Sowmya Balasubramanian1, Alejandra Kirkpatrick1

  • 1Department of Microbiology, Immunology and Molecular Genetics, University of Texas Health San Antonio, San Antonio, TX, 78229, USA.

Scientific Reports
|June 3, 2021
PubMed

Insights

Community Acquired Respiratory Distress Syndrome (CARDS) toxin, a Mycoplasma pneumoniae virulence factor, requires an acidic environment for retrograde transport to the endoplasmic reticulum. This transport is essential for toxin activation and cell vacuole formation.

Area of Science:

  • Microbiology
  • Cell Biology
  • Toxicology

Background:

  • Mycoplasma pneumoniae causes significant respiratory illness, with CARDS toxin as its primary virulence factor.
  • CARDS toxin has distinct functional domains (N-CARDS and C-CARDS) and undergoes retrograde transport after cell entry.
  • The precise mechanisms of CARDS toxin translocation and activation remain unclear.

Purpose of the Study:

  • To investigate the cellular mechanisms governing CARDS toxin transport and activation.
  • To determine the role of intracellular vesicle pH and electrical potential in CARDS toxin translocation.
  • To elucidate the pathway of CARDS toxin retrograde transport and its relation to cytotoxic effects.

Main Methods:

  • Utilized full-length CARDS toxin and mutant/truncated derivatives.
  • Employed pharmacological agents to manipulate intracellular vesicle pH and electrical potential.
  • Analyzed toxin translocation in mammalian cells using these agents.

Main Results:

  • An acidic intracellular environment is critical for CARDS toxin retrograde transport to the endoplasmic reticulum.
  • Retrograde transport is necessary for both toxin cleavage and the induction of vacuole formation.
  • CARDS toxin-induced cell vacuolation is dependent on vacuolar type-ATPase activity.

Conclusions:

  • CARDS toxin translocation to the endoplasmic reticulum is an active, pH-dependent process.
  • Retrograde transport is a key step in CARDS toxin activation and its cytotoxic mechanism.
  • Targeting vacuolar type-ATPase or acidic environments may offer therapeutic strategies against M. pneumoniae infections.

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