Evolutionary Dynamics of Vibrio cholerae O1 following a Single-Source Introduction to Haiti

Abstract

Prior to the epidemic that emerged in Haiti in October of 2010, cholera had not been documented in this country. After its introduction, a strain of Vibrio cholerae O1 spread rapidly throughout Haiti, where it caused over 600,000 cases of disease and >7,500 deaths in the first two years of the epidemic. We applied whole-genome sequencing to a temporal series of V. cholerae isolates from Haiti to gain insight into the mode and tempo of evolution in this isolated population of V. cholerae O1. Phylogenetic and Bayesian analyses supported the hypothesis that all isolates in the sample set diverged from a common ancestor within a time frame that is consistent with epidemiological observations. A pangenome analysis showed nearly homogeneous genomic content, with no evidence of gene acquisition among Haiti isolates. Nine nearly closed genomes assembled from continuous-long-read data showed evidence of genome rearrangements and supported the observation of no gene acquisition among isolates. Thus, intrinsic mutational processes can account for virtually all of the observed genetic polymorphism, with no demonstrable contribution from horizontal gene transfer (HGT). Consistent with this, the 12 Haiti isolates tested by laboratory HGT assays were severely impaired for transformation, although unlike previously characterized noncompetent V. cholerae isolates, each expressed hapR and possessed a functional quorum-sensing system. Continued monitoring of V. cholerae in Haiti will illuminate the processes influencing the origin and fate of genome variants, which will facilitate interpretation of genetic variation in future epidemics.

Genetics of Natural Competence in Vibrio cholerae and other Vibrios

“…Whole genome sequence analysis indicated the Haiti isolates were monophyletic with isolates from Nepal, in agreement with a prior hypothesis that the Haiti cholera epidemic arose from a single point source introduction from Southeast Asia (1). Importantly, genome analysis also confirmed that the regulatory and competence apparatus genes of each isolate tested for transformation proficiency were identical to uptake-proficient isolate C6706 (149), although the putative vc0857-0861 pilin-associated genes (20) had not been described at that time. The nature of the defect(s) responsible for the transformation deficiency of the Haiti isolates remains unknown, but such strains have the potential to reveal novel factors or signals that participate in competence regulation or apparatus function in V. cholerae.…”

“…A recent study of a large set of clinical V. cholerae isolates obtained during the cholera outbreak that followed the 2010 earthquake in Haiti found that each V. cholerae isolate tested was defective for natural transformation (149). Whole genome sequence analysis indicated the Haiti isolates were monophyletic with isolates from Nepal, in agreement with a prior hypothesis that the Haiti cholera epidemic arose from a single point source introduction from Southeast Asia (1).…”

Environmental Surveillance for Toxigenic Vibrio cholerae in Surface Waters of Haiti

“…JNEW01000000) clustered with Haiti clinical isolates (Supplemental Figure S1). 30 The tcpA gene was sequenced for a total of six isolates that were tcpA-positive but ctxA-negative by qPCR ( Table 5). The tcpA sequences did not match prototypical El Tor and classical tcpA sequences (Supplemental Figure S2).…”

Microbial Speciation

“…These ecological barriers might later be reinforced by genetic barriers, as sequence divergence accumulates between lineages, eventually inhibiting recombination genome-wide (stage 4). Genetic isolation may also develop more quickly if the capacity for recombination is transiently lost, either genetically (e.g., Katz et al 2013) or physiologically (e.g., by modulating expression of recombination and mismatch repair machinery).…”