Transient Glycolytic Complexation of Arsenate Enhances Resistance in the Enteropathogen Vibrio cholerae

Emilio Bueno, Víctor Pinedo, Dhananjay D. Shinde, André Mateus, Athanasios Typas, Mikhail M. Savitski, Vinai C. Thomas, Felipe Cava

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

The ubiquitous presence of toxic arsenate (AsV) in the environment has raised mechanisms of resistance in all living organisms. Generally, bacterial detoxification of AsV relies on its reduction to arsenite (AsIII) by ArsC, followed by the export of AsIII by ArsB. However, how pathogenic species resist this metalloid remains largely unknown. Here, we found that Vibrio cholerae, the etiologic agent of the diarrheal disease cholera, outcompetes other enteropathogens when grown on millimolar concentrations of AsV. To do so, V. cholerae uses, instead of ArsCB, the AsV-inducible vc1068-1071 operon (renamed var for vibrio arsenate resistance), which encodes the arsenate repressor ArsR, an alternative glyceraldehyde-3-phosphate dehydrogenase, a putative phosphatase, and the AsV transporter ArsJ. In addition to Var, V. cholerae induces oxidative stress-related systems to counter reactive oxygen species (ROS) production caused by intracellular AsV. Characterization of the var mutants suggested that these proteins function independently from one another and play critical roles in preventing deleterious effects on the cell membrane potential and growth derived from the accumulation AsV. Mechanistically, we demonstrate that V. cholerae complexes AsV with the glycolytic intermediate 3-phosphoglycerate into 1-arseno-3-phosphoglycerate (1As3PG). We further show that 1As3PG is not transported outside the cell; instead, it is subsequently dissociated to enable extrusion of free AsV through ArsJ. Collectively, we propose the formation of 1As3PG as a transient metabolic storage of AsV to curb the noxious effect of free AsV. This study advances our understanding of AsV resistance in bacteria and underscores new points of vulnerability that might be an attractive target for antimicrobial interventions.

Original languageEnglish (US)
JournalmBio
Volume13
Issue number5
DOIs
StatePublished - Sep 2022

Keywords

  • Transposon-seq
  • Vibrio cholerae
  • arsenate
  • arsenite
  • enteric pathogens

ASJC Scopus subject areas

  • Microbiology
  • Virology

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