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

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-I and -2 presence strongly correlates with pandemicity; however, the contribution of these islands to the V. cholerae 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 the V. cholerae zinc-starvation response in vitro, we noticed that a mutant constitutively expressing zinc-starvation genes (Δzur) aggregates in nutrient-poor media. Using transposon mutagenesis, we found that flagellar motility, chemotaxis, and VSP-II encoded genes are required for aggregation. 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 activator of the nearby AerB chemoreceptor. AerB interfaces with the chemotaxis system to drive oxygen-dependent autoaggregation and energy taxis. Importantly, this work suggests a functional link between VSP-II, zinc-starved environments, and aerotaxis, yielding insights into the role of VSP-II in a metal-limited host or aquatic reservoir.

Genome-wide association studies reveal distinct genetic correlates and increased heritability of antimicrobial resistance inVibrio choleraeunder anaerobic conditions

“…The GWAS hits in VSPII encode both biofilm/ auto-aggregation associated factors as well as an aerotaxis protein (AerB; VC0512) [69]; findings consistent with roles in AMR and aerobic/anaerobic conditions. These GWAS analyses were of limited power due to the modest sample size, and could be sensitive to false positives at AMR 'hot-spots' like SXT.…”

“…tet(59), aph(6)-Id, radC, dfrA31) and discovered on the Vibrio Pathogenicity Island II (VSPII; N16961 VC0506-VC0512 / E7946 loci RS02705-RS02745); these loci are genetically diverse in Bangladesh [49]. The GWAS hits in VSPII encode both biofilm/ autoaggregation associated factors as well as an aerotaxis protein (AerB; VC0512) [50]; findings consistent with roles in AMR and aerobic/ anaerobic conditions. The GWAS were limited by sample size and were at risk of increased false positive discovery rates at AMR 'hot-spots' like SXT.…”