Phosphate Limitation Modulates Vibrio Cholerae Outer Membrane Vesicle Formation, Composition and Toxicity

Area of Science:

• Microbiology
• Bacterial Pathogenesis
• Environmental Microbiology

Background:

• Vibrio cholerae thrives in low-phosphate environments, utilizing the PhoB/PhoR system for gene regulation.
• Outer membrane vesicles (OMVs) are crucial for bacterial adaptation, survival, and pathogenesis.
• Phosphate availability influences bacterial physiology and virulence.

Purpose of the Study:

• To investigate the impact of inorganic phosphate (Pi) availability on OMV production, composition, and toxicity in Vibrio cholerae.
• To determine the role of the PhoB protein in regulating OMV characteristics under Pi limitation.
• To assess the pathogenic potential of OMVs produced under varying Pi conditions.

Main Methods:

• Transmission electron microscopy (TEM), atomic force microscopy (AFM), and nanoparticle tracking analysis (NTA) for OMV characterization.
• Proteomic and lipidomic analyses to identify OMV cargo.
• Functional assays using Galleria mellonella model to evaluate OMV toxicity.

Main Results:

• OMV production significantly increased under Pi limitation, dependent on PhoB.
• OMVs from low-Pi conditions were enriched in phosphate-regulated proteins and phosphorus-free lipids.
• OMVs produced under Pi limitation exhibited significantly higher toxicity in Galleria mellonella.

Conclusions:

• Phosphate limitation is a key environmental cue that modulates Vibrio cholerae OMV production and composition.
• OMVs serve as dynamic effectors, enhancing bacterial adaptation to low-Pi stress and increasing pathogenicity.
• Targeting OMV biogenesis or cargo could be a strategy to control Vibrio cholerae infections.