Deciphering the Origins and Tracking the Evolution of Cholera Epidemics with Whole-Genome-Based Molecular Epidemiology (original) (raw)
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Genomic diversity of 2010 Haitian cholera outbreak strains
Proceedings of the National Academy of Sciences, 2012
The millions of deaths from cholera during the past 200 y, coupled with the morbidity and mortality of cholera in Haiti since October 2010, are grim reminders that Vibrio cholerae , the etiologic agent of cholera, remains a scourge. We report the isolation of both V . cholerae O1 and non-O1/O139 early in the Haiti cholera epidemic from samples collected from victims in 18 towns across eight Arrondissements of Haiti. The results showed two distinct populations of V. cholerae coexisted in Haiti early in the epidemic. As non-O1/O139 V . cholerae was the sole pathogen isolated from 21% of the clinical specimens, its role in this epidemic, either alone or in concert with V . cholerae O1, cannot be dismissed. A genomic approach was used to examine similarities and differences among the Haitian V . cholerae O1 and V . cholerae non-O1/O139 strains. A total of 47 V . cholerae O1 and 29 V . cholerae non-O1/O139 isolates from patients and the environment were sequenced. Comparative genome anal...
Evolutionary Dynamics of Vibrio cholerae O1 following a Single-Source Introduction to Haiti
mBio, 2013
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. IMPORTANCE Vibrio cholerae is the cause of substantial morbidity and mortality worldwide, with over three million cases of disease each year. An understanding of the mode and rate of evolutionary change is critical for proper interpretation of genome sequence data and attribution of outbreak sources. The Haiti epidemic provides an unprecedented opportunity to study an isolated, single-source outbreak of Vibrio cholerae O1 over an established time frame. By using multiple approaches to assay genetic variation, we found no evidence that the Haiti strain has acquired any genes by horizontal gene transfer, an observation that led us to discover that it is also poorly transformable. We have found no evidence that environmental strains have played a role in the evolution of the outbreak strain.
High depth, whole-genome sequencing of cholera isolates from Haiti and the Dominican Republic
2012
Background: Whole-genome sequencing is an important tool for understanding microbial evolution and identifying the emergence of functionally important variants over the course of epidemics. In October 2010, a severe cholera epidemic began in Haiti, with additional cases identified in the neighboring Dominican Republic. We used whole-genome approaches to sequence four Vibrio cholerae isolates from Haiti and the Dominican Republic and three additional V. cholerae isolates to a high depth of coverage (>2000x); four of the seven isolates were previously sequenced. Results: Using these sequence data, we examined the effect of depth of coverage and sequencing platform on genome assembly and identification of sequence variants. We found that 50x coverage is sufficient to construct a whole-genome assembly and to accurately call most variants from 100 base pair paired-end sequencing reads. Phylogenetic analysis between the newly sequenced and thirty-three previously sequenced V. cholerae isolates indicates that the Haitian and Dominican Republic isolates are closest to strains from South Asia. The Haitian and Dominican Republic isolates form a tight cluster, with only four variants unique to individual isolates. These variants are located in the CTX region, the SXT region, and the core genome. Of the 126 mutations identified that separate the Haiti-Dominican Republic cluster from the V. cholerae reference strain (N16961), 73 are non-synonymous changes, and a number of these changes cluster in specific genes and pathways.
Environmental Microbiology Reports, 2010
Vibrio cholerae O1 El Tor BX 330286 was isolated from a water sample in Australia in 1986, 9 years after an indigenous outbreak of cholera occurred in that region. This environmental strain encodes virulence factors highly similar to those of clinical strains, suggesting an ability to cause disease in humans. We demonstrate its high similarity in gene content and genome-wide nucleotide sequence to clinical V. cholerae strains, notably to pre-seventh pandemic O1 El Tor strains isolated in 1910 (V. cholerae NCTC 8457) and 1937 (V. cholerae MAK 757), as well as seventh pandemic strains isolated after 1960 globally. Here we demonstrate that this strain represents a transitory clone with shared characteristics between pre-seventh and seventh pandemic strains of V. cholerae. Interestingly, this strain was isolated 25 years after the beginning of the seventh pandemic, suggesting the environment as a genome reservoir in areas where cholera does not occur in sporadic, endemic or epidemic form.
Evolutionary perspective on the origin of Haitian cholera outbreak strain
Cholera epidemic has not been reported in Haiti for at least 100 years, although cholera has been present in Latin America since 1991. Surprisingly, the recent cholera epidemic in Haiti (October 2010) recorded more than 250,000 cases and 4000 deaths in the first 6 months and became one of the most explosive and deadly cholera outbreak in recent history. In the present study, we conducted genomic analyses of pathogenicity islands of three Haitian Vibrio cholerae strains and compared them with nine different V. cholerae O1 El Tor genomes. Although CIRS101 is evolutionarily most similar to the Haitian strains, our study also provides some important differences in the genetic organization of pathogenicity islands of Haitian strains with CIRS101. Evolutionary analysis suggests that unusual functional constraints have been imposed on the Haitian strains and we hypothesize that amino acid substitution is more deleterious in Haitian strains than in nonHaitian strains.
mBio, 2011
Cholera continues to be an important cause of human infections, and outbreaks are often observed after natural disasters, such as the one following the 2010 earthquake in Haiti. Once the cholera outbreak was confirmed, rumors spread that the disease was brought to Haiti by a battalion of Nepalese soldiers serving as United Nations peacekeepers. This possible connection has never been confirmed. We used whole-genome sequence typing (WGST), pulsed-field gel electrophoresis (PFGE), and antimicrobial susceptibility testing to characterize 24 recent Vibrio cholerae isolates from Nepal and evaluate the suggested epidemiological link with the Haitian outbreak. The isolates were obtained from 30 July to 1 November 2010 from five different districts in Nepal. We compared the 24 genomes to 10 previously sequenced V. cholerae isolates, including 3 from the Haitian outbreak (began July 2010). Antimicrobial susceptibility and PFGE patterns were consistent with an epidemiological link between the isolates from Nepal and Haiti. WGST showed that all 24 V. cholerae isolates from Nepal belonged to a single monophyletic group that also contained isolates from Bangladesh and Haiti. The Nepalese isolates were divided into four closely related clusters. One cluster contained three Nepalese isolates and three Haitian isolates that were almost identical, with only 1-or 2-bp differences.
Environmental Microbiology Reports, 2010
Vibrio cholerae O1 El Tor BX 330286 was isolated from a water sample in Australia in 1986, 9 years after an indigenous outbreak of cholera occurred in that region. This environmental strain encodes virulence factors highly similar to those of clinical strains, suggesting an ability to cause disease in humans. We demonstrate its high similarity in gene content and genome-wide nucleotide sequence to clinical V. cholerae strains, notably to pre-seventh pandemic O1 El Tor strains isolated in 1910 (V. cholerae NCTC 8457) and 1937 (V. cholerae MAK 757), as well as seventh pandemic strains isolated after 1960 globally. Here we demonstrate that this strain represents a transitory clone with shared characteristics between preseventh and seventh pandemic strains of V. cholerae. Interestingly, this strain was isolated 25 years after the beginning of the seventh pandemic, suggesting the environment as a genome reservoir in areas where cholera does not occur in sporadic, endemic or epidemic form.