title: Phylodynamic analysis of clinical and environmental Vibrio cholerae isolates from Haiti reveals diversification driven by positive selection.
abstract: Phylodynamic analysis of genome-wide single-nucleotide polymorphism (SNP) data is a powerful tool to investigate underlying evolutionary processes of bacterial epidemics. The method was applied to investigate a collection of 65 clinical and environmental isolates of Vibrio cholerae from Haiti collected between 2010 and 2012. Characterization of isolates recovered from environmental samples identified a total of four toxigenic V. cholerae O1 isolates, four non-O1/O139 isolates, and a novel nontoxigenic V. cholerae O1 isolate with the classical tcpA gene. Phylogenies of strains were inferred from genome-wide SNPs using coalescent-based demographic models within a Bayesian framework. A close phylogenetic relationship between clinical and environmental toxigenic V. cholerae O1 strains was observed. As cholera spread throughout Haiti between October 2010 and August 2012, the population size initially increased and then fluctuated over time. Selection analysis along internal branches of the phylogeny showed a steady accumulation of synonymous substitutions and a progressive increase of nonsynonymous substitutions over time, suggesting diversification likely was driven by positive selection. Short-term accumulation of nonsynonymous substitutions driven by selection may have significant implications for virulence, transmission dynamics, and even vaccine efficacy.
  
  
  OBJECTIVE
  Cholera, a dehydrating diarrheal disease caused by toxigenic strains of the bacterium Vibrio cholerae, emerged in 2010 in Haiti, a country where there were no available records on cholera over the past 100 years. While devastating in terms of morbidity and mortality, the outbreak provided a unique opportunity to study the evolutionary dynamics of V. cholerae and its environmental presence. The present study expands on previous work and provides an in-depth phylodynamic analysis inferred from genome-wide single nucleotide polymorphisms of clinical and environmental strains from dispersed geographic settings in Haiti over a 2-year period. Our results indicate that even during such a short time scale, V. cholerae in Haiti has undergone evolution and diversification driven by positive selection, which may have implications for understanding the global clinical and epidemiological patterns of the disease. Furthermore, the continued presence of the epidemic strain in Haitian aquatic environments has implications for transmission.
authors.forename: Taj
authors.initials: T
authors.lastname: Azarian
authors.forename: Afsar
authors.initials: A
authors.lastname: Ali
authors.forename: Judith A
authors.initials: JA
authors.lastname: Johnson
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: David
authors.initials: D
authors.lastname: Mohr
authors.forename: Mattia
authors.initials: M
authors.lastname: Prosperi
authors.affiliation: Emerging Pathogens Institute, University of Florida, Gainesville, Florida, USA.
authors.forename: Nazle M
authors.initials: NM
authors.lastname: Veras
authors.forename: Mohammed
authors.initials: M
authors.lastname: Jubair
authors.affiliation: Emerging Pathogens Institute, University of Florida, Gainesville, Florida, USA.
authors.forename: Samantha L
authors.initials: SL
authors.lastname: Strickland
authors.affiliation: Emerging Pathogens Institute, University of Florida, Gainesville, Florida, USA.
authors.forename: Mohammad H
authors.initials: MH
authors.lastname: Rashid
authors.affiliation: Emerging Pathogens Institute, University of Florida, Gainesville, Florida, USA.
authors.forename: Meer T
authors.initials: MT
authors.lastname: Alam
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Weppelmann
authors.affiliation: Enteric Diseases Laboratory Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Lee S
authors.initials: LS
authors.lastname: Katz
authors.affiliation: Enteric Diseases Laboratory Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Tarr
authors.forename: Rita R
authors.initials: RR
authors.lastname: Colwell
authors.affiliation: Emerging Pathogens Institute, University of Florida, Gainesville, Florida, USA salemi@pathology.ufl.edu jgmorris@epi.ufl.edujgmorris@epi.ufl.edu.
authors.forename: J Glenn
authors.initials: JG
authors.lastname: Morris
authors.affiliation: salemi@pathology.ufl.edu jgmorris@epi.ufl.edujgmorris@epi.ufl.edu.
authors.forename: Marco
authors.initials: M
authors.lastname: Salemi
mesh_terms: D002771:Cholera / Q000453:epidemiology* / Q000382:microbiology*; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D004783:Environmental Microbiology; D019143:Evolution, Molecular; D014644:Genetic Variation; D006205:Haiti / Q000453:epidemiology; D020125:Mutation, Missense; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D041241:Vibrio cholerae O1 / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification; D041242:Vibrio cholerae O139 / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification
chemical_list: D004269:DNA, Bacterial