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

PLoS Genet. 2021 Jun 21;17(6):e1009624. doi: 10.1371/journal.pgen.1009624. eCollection 2021 Jun.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Bacterial Adhesion
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Chemotaxis / genetics*
  • Cholera / microbiology
  • Cholera / pathology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation, Bacterial*
  • Genes, Reporter
  • Genome, Bacterial
  • Genomic Islands*
  • Humans
  • Lac Operon
  • Oxygen / metabolism
  • Oxygen / pharmacology
  • Pandemics
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Transcription, Genetic
  • Vibrio cholerae / drug effects
  • Vibrio cholerae / genetics*
  • Vibrio cholerae / metabolism
  • Vibrio cholerae / pathogenicity*
  • Zinc / deficiency*
  • Zinc / pharmacology


  • Bacterial Proteins
  • DNA-Binding Proteins
  • Repressor Proteins
  • Zinc
  • Oxygen