Phenotypic Analysis Reveals that the 2010 Haiti Cholera Epidemic Is Linked to a Hypervirulent Strain

Abstract

bVibrio cholerae O1 El Tor strains have been responsible for pandemic cholera since 1961. These strains have evolved over time, spreading globally in three separate waves. Wave 3 is caused by altered El Tor (AET) variant strains, which include the strain with the signature ctxB7 allele that was introduced in 2010 into Haiti, where it caused a devastating epidemic. In this study, we used phenotypic analysis to compare an early isolate from the Haiti epidemic to wave 1 El Tor isolates commonly used for research. It is demonstrated that the Haiti isolate has increased production of cholera toxin (CT) and hemolysin, increased motility, and a reduced ability to form biofilms. This strain also outcompetes common wave 1 El Tor isolates for colonization of infant mice, indicating that it has increased virulence. Monitoring of CT production and motility in additional wave 3 isolates revealed that this phenotypic variation likely evolved over time rather than in a single genetic event. Analysis of available whole-genome sequences and phylogenetic analyses suggested that increased virulence arose from positive selection for mutations found in known and putative regulatory genes, including hns and vieA, diguanylate cyclase genes, and genes belonging to the lysR and gntR regulatory families. Overall, the studies presented here revealed that V. cholerae virulence potential can evolve and that the currently prevalent wave 3 AET strains are both phenotypically distinct from and more virulent than many El Tor isolates.

H-NS: an overarching regulator of the Vibrio cholerae life cycle

“…Although the causes of the V. cholerae O1 population shift from classical to El Tor biotypes are not clearly understood, loss of H-NS in El Tor biotype V. cholerae mimics an evolutionary backward change. A recent study of wave 3 El Tor O1 strains isolated during the 2010 cholera outbreak in Haiti revealed that these isolates, which express elevated CT and hemolysin compared to earlier wave 1 strains, harbored mutations in the hns gene [45]. This finding highlights the importance of H-NS transcriptional silencing and antirepression in pathogen evolution.…”

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

“…These strains have spread globally in three separate waves [3]. While acquiring numerous changes in their genetic background, wave 3 altered El Tor (AET) strains have propagated through many of the cholera endemic regions in Asia and Africa [4]. After the 2010 earthquake in Haiti, a disastrous cholera outbreak emerged in late October which affected over 600,000 people, resulting in deaths of around 8000 Haitians [5].…”

The ins and outs of cyclic di-GMP signaling in Vibrio cholerae

“…Cellular c-di-GMP levels vary in different V. cholerae isolates [7]. Thus, when tested in different V. cholerae genetic backgrounds, additional DGCs and PDEs were shown to govern motility.…”