Haitian Variant Vibrio cholerae O1 Strains Manifest Higher Virulence in Animal Models

Abstract

Vibrio cholerae causes fatal diarrheal disease cholera in humans due to consumption of contaminated water and food. To instigate the disease, the bacterium must evade the host intestinal innate immune system; penetrate the mucus layer of the small intestine, adhere and multiply on the surface of microvilli and produce toxin(s) through the action of virulence associated genes. V. cholerae O1 that has caused a major cholera outbreak in Haiti contained several unique genetic signatures. These novel traits are used to differentiate them from the canonical El Tor strains. Several studies reported the spread of these Haitian variant strains in different parts of the world including Asia and Africa, but there is a paucity of information on the clinical consequence of these genetic changes. To understand the impact of these changes, we undertook a study involving mice and rabbit models to evaluate the pathogenesis. The colonization ability of Haitian variant strain in comparison to canonical El Tor strain was found to be significantly more in both suckling mice and rabbit model. Adult mice also displayed the same results. Besides that, infection patterns of Haitian variant strains showed a completely different picture. Increased mucosal damaging, colonization, and inflammatory changes were observed through hematoxylin-eosin staining and transmission electron microscopy. Fluid accumulation ability was also significantly higher in rabbit model. Our study indicated that these virulence features of the Haitian variant strain may have some association with the severe clinical outcome of the cholera patients in different parts of the world.

Deciphering the possible role of ctxB7 allele on higher production of cholera toxin by Haitian variant Vibrio cholerae O1

“…Increased pathogenic potential was directly demonstrated as the hypervirulent strain outcompeted other strains in cocolonization studies. Furthermore, one of the recent reports from our group has also shown that Haitian variant strains of Vibrio cholerae O1 displayed higher virulence in animal models [17]. However, it was not previously known whether the H20N change in ctxB7 may have contributed to hypertoxigenic phenotype of the Haiti variant isolates.…”

“…Furthermore, Haitian outbreak strain had also been found to exhibit characteristics of hypervirulence with increased pathogenic potential [4]. Recently, one of the reports from our group has shown that Haitian variant strains of Vibrio cholerae O1 manifested markedly higher fluid accumulation and increased mucosal damage in animal models [17]. However, it was not previously known whether the ctxB7 allele may have contributed to hypertoxigenic phenotype of these atypical variants isolates.…”

Cholera Toxin Production in Vibrio cholerae O1 El Tor Biotype Strains in Single-Phase Culture

“…IB5230 is considered a hypervirulent strain due to its elevated CT production and colonization of the intestine (Satchell et al, 2016;Ghosh et al, 2019). The CT that was produced by this strain is ctxB7, which differs from the classical type ctxB (ctxB1) at amino acid residue 20.…”

Haitian-like genetic traits with creeping MIC of Azithromycin in Vibrio cholerae O1 isolates from Puducherry, India

“…This is in line with studies from other regions, such as a study from Kolkata, India, which reports strains possessing Haitianlike traits across 12 states. Evolution of the variant El Tors has offered heightened virulence and toxigenicity as they produce classical cholera toxin that produces more severe disease [39][40][41]. The emergence of polymyxin B susceptibility, one of the traits of classical biotype in recent years, suggest that El Tor biotype strains have morphed into the classical biotype [8].…”