Single Nucleotide Polymorphisms in Regulator-Encoding Genes Have an Additive Effect on Virulence Gene Expression in a Vibrio cholerae Clinical Isolate

Abstract

Cholera, an infectious disease of the small intestine caused by the aquatic bacterium Vibrio cholerae, often results in vomiting and acute watery diarrhea. If left untreated or if the response is too slow, the symptoms can quickly lead to extreme dehydration and ultimately death of the patient. Recent anecdotal evidence of cholera patients suffering from increasingly severe symptoms and of disease progression at a much higher rate than previously observed has emerged. As recent cholera outbreaks caused by increasingly virulent strains have resulted in higher mortality rates, the need to investigate the mechanism(s) allowing this observed increased virulence is apparent. The significance of our research is in identifying the mechanism for increased virulence capabilities, which will allow the development of a model that will greatly enhance our understanding of cholera disease and V. cholerae pathogenesis, leading to broader biomedical impacts, as cholera serves as a model for other enteric diarrheal diseases.

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

“…Previous studies support that V. cholerae O1 strains with the ctxB7 allele produce excess CT compared to prototypical El Tor isolates [4,14]. This excess toxin production has been attributed in part to change in virulence gene regulation due to single nucleotide substitutions in hns [15] encoding the histone-like nucleoid structuring protein (H-NS) and vieA [16], encoding a cyclic diguanylic acid (c-di-GMP) phosphodiesterase (PDE). Furthermore, Haitian outbreak strain had also been found to exhibit characteristics of hypervirulence with increased pathogenic potential [4].…”

Molecular basis for the differential expression of the global regulator VieA in Vibrio cholerae biotypes directed by H‐NS, LeuO and quorum sensing

“…Genome sequencing of these strains revealed the presence of mutations in the regulatory genes hns , encoding the histone-like nucleoid structuring protein (H-NS) and vieA , encoding a cyclic diguanylic acid (c-di-GMP) phosphodiesterase (PDE) (Satchell et al , 2016). Transfer of hns and vieA single nucleotide polymorphisms (SNPs) from a wave 3 strain into a prototype wave 1 strain resulted in a hypervirulent phenotype (Carignan et al , 2016). These results suggest that natural selection of strains containing mutations in the above loci could be contributing to the increased severity and duration of recent cholera outbreaks.…”

Growth and Maintenance of Escherichia coli Laboratory Strains

“…For its genetic tractability and ease of use for recombinant DNA research, in addition to the nonpathogenic nature of the E. coli K‐12 and B strains making them safe for recombinant DNA work, E. coli has remained a model organism, as clearly demonstrated by the work of Roy Curtiss in 1978 (Curtiss, 1978) and reviewed by Reed and Palsson (2003) and Blount (2015). The use of E. coli in conjugation and allelic exchange in different bacterial genera is described in Skorupski and Taylor (1996) and Carignan, Brumfield, and Son (2016).…”