Vibrio cholerae can Recycle Fatty Acids Via an Acyl-Acyl Carrier Protein Synthetase

Area of Science:

• Microbiology
• Biochemistry
• Molecular Biology

Background:

• Fatty acids are essential molecules synthesized by fatty acid synthase (FAS).
• Certain antibiotics target bacterial FAS, but bacteria can evade inhibition by utilizing exogenous fatty acids.
• Acyl-acyl carrier protein synthetase (AasS) enables direct fatty acid utilization, bypassing the need for beta-oxidation.

Purpose of the Study:

• To identify and characterize the acyl-acyl carrier protein synthetase (AasS) in Vibrio cholerae.
• To investigate the role of AasS in V. cholerae's ability to utilize exogenous fatty acids.
• To explore the potential of targeting AasS or FAS in V. cholerae for antibiotic development.

Main Methods:

• Unnatural fatty acid supplementation and mass spectrometry were employed to identify AasS in V. cholerae.
• In vitro enzyme assays were performed to characterize the substrate specificity of V. cholerae AasS.
• Growth inhibition assays using FAS-targeted antibiotics and fatty acid supplementation were conducted on wild-type and AasS deletion strains of V. cholerae.

Main Results:

• The AasS enzyme from Vibrio cholerae was identified and characterized.
• V. cholerae AasS was shown to load diverse fatty acids onto the FAS acyl carrier protein and coenzyme A.
• FAS-targeted antibiotics inhibited wild-type V. cholerae growth, but this inhibition was rescued by fatty acid supplementation.
• An AasS deletion strain demonstrated growth in the presence of cerulenin and fatty acids, highlighting redundant utilization pathways.

Conclusions:

• Vibrio cholerae possesses an AasS enzyme that facilitates the direct utilization of exogenous fatty acids.
• Fatty acid supplementation can rescue growth inhibition caused by FAS-targeted antibiotics in V. cholerae.
• The study reveals the redundancy of environmental fatty acid utilization in V. cholerae, mediated by AasS.