A Combination of Metagenomic and Cultivation Approaches Reveals Hypermutator Phenotypes within Vibrio cholerae-Infected Patients
Inès Levade, Ashraful Islam Khan, Fahima Chowdhury, Stephen B. Calderwood, Edward T. Ryan, Jason B. Harris, Regina C. LaRocque, Taufiqur Rahman Bhuiyan, Firdausi Qadri, Ana A. Weil, B. Jesse Shapiro
Abstract
Pathogen evolution within patients can impact phenotypes such as drug resistance and virulence, potentially affecting clinical outcomes. V. cholerae infection can result in life-threatening diarrheal disease or asymptomatic infection. Here, we describe whole-genome sequencing of V. cholerae isolates and culture-free metagenomic sequencing from stool of symptomatic cholera patients and asymptomatic carriers. Despite the typically short duration of cholera, we found evidence for adaptive mutations in the V. cholerae genome that occur independently and repeatedly within multiple symptomatic patients. We also identified V. cholerae hypermutator phenotypes within several patients, which appear to generate mainly neutral or deleterious mutations. Our work sets the stage for future studies of the role of hypermutators and within-patient evolution in explaining the variation from asymptomatic carriage to symptomatic cholera.