Genomic characteristics of recently recognized Vibrio cholerae El Tor lineages associated with cholera in Bangladesh, 1991-2017

Comparative genomic analysis of Vibrio cholerae El Tor associated with endemic cholera in Asia revealed two distinct lineages, one dominant in Bangladesh and the other in India. An in depth whole genome study of V. cholerae El Tor clinical strains isolated during endemic cholera in Bangladesh (1991 – 2017) included reference genome sequence data obtained online. Core genome phylogeny established using single nucleotide polymorphisms (SNPs) showed V. choleraeEl Tor strains comprised two lineages, BD-1 and BD-2, which, according to Bayesian phylodynamic analysis, originated from paraphyletic group BD-0 around 1981. BD-1 and BD-2 lineages overlapped temporally but were negatively associated as causative agents of cholera 2004-2017. Genome wide association study (GWAS) revealed 140 SNPs and 31 indels, resulting in gene alleles unique to BD-1 and BD-2. Regression analysis of root to tip distance and year of isolation indicated early BD-0 strains at the base, whereas BD-1 and BD-2 subsequently emerged and progressed by accumulating SNPs. Pangenome analysis provided evidence of gene acquisition by both BD-1 and BD-2, of which six crucial proteins of known function were predominant in BD-2. BD-1 and BD-2 diverged and have distinctively different genomic traits, namely heterogeneity in VSP-2, VPI-1, mobile elements, toxin encoding elements, and total gene abundance. In addition, the observed phage-inducible chromosomal island-like element (PLE1), and SXT ICE elements (ICETET) in BD-2 presumably provided a fitness advantage for the lineage to outcompete BD-1 as the etiological agent of the endemic cholera in Bangladesh, with implications for global cholera epidemiology.

Mathematical modeling of endemic cholera transmission

Mathematical modeling can be used to project the impact of mass vaccination on cholera transmission. Here, we discuss two examples for which indirect protection from mass vaccination needs to be considered. In the first, we show that non-vaccinees can be protected by mass vaccination campaigns. This additional benefit of indirect protection improves the cost-effectiveness of mass vaccination. In the second, we model the use of mass vaccination to eliminate cholera. In this case, a high population level of immunity, including contributions from infection and vaccination, is required to reach the “herd immunity” threshold needed to stop transmission and achieve elimination.

Genomics of the Argentinian cholera epidemic elucidate the contrasting dynamics of epidemic and endemic Vibrio cholerae

In order to control and eradicate epidemic cholera, we need to understand how epidemics begin, how they spread, and how they decline and eventually end. This requires extensive sampling of epidemic disease over time, alongside the background of endemic disease that may exist concurrently with the epidemic. The unique circumstances surrounding the Argentinian cholera epidemic of 1992–1998 presented an opportunity to do this. Here, we use 490 Argentinian V. cholerae genome sequences to characterise the variation within, and between, epidemic and endemic V. cholerae. We show that, during the 1992–1998 cholera epidemic, the invariant epidemic clone co-existed alongside highly diverse members of the Vibrio cholerae species in Argentina, and we contrast the clonality of epidemic V. cholerae with the background diversity of local endemic bacteria. Our findings refine and add nuance to our genomic definitions of epidemic and endemic cholera, and are of direct relevance to controlling current and future cholera epidemics.

Analysis of 19 Highly Conserved Vibrio cholerae Bacteriophages Isolated from Environmental and Patient Sources Over a Twelve-Year Period

The Vibrio cholerae biotype ‘El Tor’ is responsible for all current epidemic and endemic cholera outbreaks worldwide. These outbreaks are clonal and are hypothesized to originate from the coastal areas near the Bay of Bengal where the lytic bacteriophage ICP1 specifically preys upon these pathogenic outbreak strains. ICP1 has also been the dominant bacteriophage found in cholera patient stool since 2001. However, little is known about its genomic differences between ICP1 strains collected over time. Here we elucidate the pan-genome and phylogeny of ICP1 strains by aligning, annotating and analyzing the genomes of 19 distinct isolates collected between 2001 and 2012. Our results reveal that ICP1 isolates are highly conserved and possess a large core-genome as well as a smaller, somewhat flexible accessory-genome. Despite its overall conservation, ICP1 strains have managed to acquire a number of unknown genes as well as a CRISPR-Cas system, which is known to be critical for its ongoing struggle for co-evolutionary dominance over its host. This study describes a foundation on which to construct future molecular and bioinformatic studies of this V. cholerae-associated bacteriophages.

PREVALENCE OF ICE ELEMENTS OF DIFFERENT TYPES IN V. CHOLERAE

With the help of a virtual PCR in silico analysis of the local database 395 genome-nucleotide sequences of Vibrio cholerae in the presence of ICE element. The results showed widespread ICE member from toxigenic strains and nontoxigenic Vibrio cholerae O1 serotype. Thus all elements of ICE successfully typed three basic types – «Indian», «Mozambique», or «the SXT». In this case up to 40 % nontoxigenic strains O1 serovar and nonO1/nonO139 carried ICE element. When analyzed by PCR in vitro collection of 222 strains of Vibrio cholerae O1 serotype shows the presence of ICE element and determine its type in toxigenic strains isolated in recent years in the Russian Federation. All nontoxigenic O1, O139 and nonO1/nonO139 strains isolated in Russia, deprived of ICE element that differs from strains circulating in endemic cholera areas. This observation allows us to consider the presence of ICE element as a new epidemic marker «of invasive strains of» nontoxigenic Vibrio cholerae.

Imported cholera with acute renal failure after a short business-trip to the Philippines, Germany, October 2015

A German businessman developed acute watery diarrhoea after a three-day trip to the Philippines. He was admitted with severe hypotension and acute renal failure, but recovered with rapid rehydration. Vibrio cholerae O1 serotype Ogawa was isolated. Physicians need to be aware of endemic cholera in Asia including the Philippines and consider this in their pre-travel advice.