Vibrio cholerae genomic diversity within and between patients

Area of Science:

• Microbiology
• Genomics
• Evolutionary biology

Background:

• Cholera is a severe diarrheal disease caused by Vibrio cholerae.
• Previous studies show large-scale V. cholerae evolution over decades.
• Intra-patient V. cholerae genetic diversity remains poorly understood.

Purpose of the Study:

• To characterize V. cholerae genomic diversity at a micro-epidemiological level within individual patients.
• To investigate point mutations and gene gain/loss events within hosts.
• To understand the phenotypic consequences of intra-host V. cholerae evolution.

Main Methods:

• Sequencing genomes of multiple V. cholerae isolates (8-20) per patient.
• Identifying single nucleotide variants (SNVs) and gene content variation.
• Analyzing phage and plasmid dynamics and horizontal gene transfer.

Main Results:

• Limited point mutation diversity (0-3 SNVs) but significant gene content variation (up to 103 events) within patients.
• Gene content changes largely driven by phage and plasmid acquisition/loss.
• Intra-host variants demonstrated phenotypic effects, reducing biofilm formation.

Conclusions:

• Vibrio cholerae measurably evolves within individual patients.
• Intra-host evolution involves significant gene content flux, particularly phage and plasmids.
• Intra-host evolution has phenotypic consequences, potentially impacting cholera transmission and outcomes.