Vibrio cholerae’s mysterious Seventh Pandemic island (VSP-II) encodes novel Zur-regulated zinc starvation genes involved in chemotaxis and cell congregation

Abstract

Vibrio cholerae is the causative agent of cholera, a notorious diarrheal disease that is typically transmitted via contaminated drinking water. The current pandemic agent, the El Tor biotype, has undergone several genetic changes that include horizontal acquisition of two genomic islands (VSP-I and VSP-II). VSP presence strongly correlates with pandemicity; however, the contribution of these islands to V. cholerae’s life cycle, particularly the 26-kb VSP-II, remains poorly understood. VSP-II-encoded genes are not expressed under standard laboratory conditions, suggesting that their induction requires an unknown signal from the host or environment. One signal that bacteria encounter under both host and environmental conditions is metal limitation. While studying V. cholerae’s zinc-starvation response in vitro, we noticed that a mutant constitutively expressing zinc starvation genes (Δzur) congregates at the bottom of a culture tube when grown in a nutrient-poor medium. Using transposon mutagenesis, we found that flagellar motility, chemotaxis, and VSP-II encoded genes were required for congregation. The VSP-II genes encode an AraC-like transcriptional activator (VerA) and a methyl-accepting chemotaxis protein (AerB). Using RNA-seq and lacZ transcriptional reporters, we show that VerA is a novel Zur target and an activator of the nearby AerB chemoreceptor. AerB interfaces with the chemotaxis system to drive oxygen-dependent congregation and energy taxis. Importantly, this work suggests a functional link between VSP-II, zinc-starved environments, and energy taxis, yielding insights into the role of VSP-II in a metal-limited host or aquatic reservoir.

The Vibrio cholerae Seventh Pandemic Islands act in tandem to defend against a circulating phage

“…For years only the island’s integrase and cognate recombination directionality factor were known [ 13 ]. It was recently discovered that a gene cluster in VSP-II ( vc0513-0515 ) is a part of the zinc-dependent Zur regulon [ 22 ]. Specifically, vc0513 encodes a transcriptional activator VerA to activate expression of vc0512 ( aerB) to alter chemotaxis and aggregation in an oxygen dependent manner.…”

Vibrio cholerae requires oxidative respiration through the bd-I and cbb3 oxidases for intestinal proliferation

“…Oxygen sensing may also drive a chemotactic response in V . cholerae through aerotactic chemoreceptors Aer1 [ 55 ] and Aer2 [ 56 ], however this oxygen response pathway is unlikely to be required in vivo as non-chemotactic V . cholerae nevertheless colonize the infant mouse intestine [ 57 ].…”

Contribution of microbial genomics to cholera epidemiology

“…Comparative genomics studies identified two genomic islands, VSP-I and VSP-II, characteristic of strains of the 7PET lineage [11,28]. The genes of these islands are thought to be involved in bacteriophage resistance and bacterial chemotaxis [31,32].…”

“…Par génomique comparative, il a été possible d'identifier deux îlots génomiques, VSP-I et VSP-II, caractéristiques des souches de la lignée 7PET [11,28]. Des gènes de ces îlots auraient un rôle dans la résistance aux bactériophages et dans le chimiotactisme bactérien [31,32].…”