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Updated: Aug 26, 2025

Detection of Toxin Translocation into the Host Cytosol by Surface Plasmon Resonance
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V. cholerae MakA is a cholesterol-binding pore-forming toxin that induces non-canonical autophagy

Xiaotong Jia1,2, Anastasia Knyazeva1,2, Yu Zhang1,2

  • 1Department of Chemistry, Umeå University, Umeå, Sweden.

The Journal of Cell Biology
|October 4, 2022
PubMed

Insights

Vibrio cholerae toxin MakA is a novel cholesterol-binding pore-forming toxin (PFT). It induces autophagy by forming pores in a pH-dependent manner, revealing a new mechanism of host cell manipulation.

Area of Science:

  • Microbiology
  • Cell Biology
  • Toxicology

Background:

  • Pore-forming toxins (PFTs) are key virulence factors in bacterial pathogens.
  • Understanding toxin-host interactions is crucial for developing antimicrobial strategies.

Purpose of the Study:

  • To characterize the Vibrio cholerae toxin MakA as a novel cholesterol-binding PFT.
  • To elucidate the mechanism of MakA-induced autophagy and host cell manipulation.

Main Methods:

  • Biochemical assays to assess cholesterol binding and pore formation.
  • Cell-based assays to investigate autophagy induction and membrane repair mechanisms.
  • Site-directed mutagenesis to identify key residues for MakA-cholesterol interaction.

Main Results:

  • MakA is a novel cholesterol-binding PFT that oligomerizes and forms pores at acidic pH.
  • MakA utilizes a unique Ile-Ile motif for cholesterol interaction, distinct from other cholesterol-dependent cytolysins.
  • MakA triggers non-canonical autophagy via V-ATPase-dependent LC3 lipidation on damaged endolysosomal membranes.

Conclusions:

  • MakA represents a new class of cholesterol-binding PFTs with pH-dependent pore formation.
  • MakA's mechanism involves ESCRT-mediated membrane repair and induction of host autophagy.
  • This study reveals novel insights into bacterial toxin function and host-pathogen interactions.

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