The metabolite vanillic acid regulates Acinetobacter baumannii surface attachment

Mol Microbiol. 2024 May;121(5):833-849. doi: 10.1111/mmi.15234. Epub 2024 Feb 3.

Abstract

The nosocomial bacterium Acinetobacter baumannii is protected from antibiotic treatment by acquiring antibiotic resistances and by forming biofilms. Cell attachment, one of the first steps in biofilm formation, is normally induced by environmental metabolites. We hypothesized that vanillic acid (VA), the oxidized form of vanillin and a widely available metabolite, may play a role in A. baumannii cell attachment. We first discovered that A. baumannii actively breaks down VA through the evolutionarily conserved vanABKP genes. These genes are under the control of the repressor VanR, which we show binds directly to VanR binding sites within the vanABKP genes bidirectional promoter. VA in turn counteracts VanR inhibition. We identified a VanR binding site and searched for it throughout the genome, especially in pili encoding promoter genes. We found a VanR binding site in the pilus encoding csu operon promoter and showed that VanR binds specifically to it. As expected, a strain lacking VanR overproduces Csu pili and makes robust biofilms. Our study uncovers the role that VA plays in facilitating the attachment of A. baumannii cells to surfaces, a crucial step in biofilm formation. These findings provide valuable insights into a previously obscure catabolic pathway with significant clinical implications.

Keywords: Acinetobacter baumannii; VanR; biofilm; catabolism; vanillic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinetobacter baumannii* / drug effects
  • Acinetobacter baumannii* / genetics
  • Acinetobacter baumannii* / metabolism
  • Bacterial Adhesion*
  • Bacterial Proteins* / genetics
  • Bacterial Proteins* / metabolism
  • Benzaldehydes / metabolism
  • Benzaldehydes / pharmacology
  • Binding Sites
  • Biofilms* / growth & development
  • Fimbriae, Bacterial* / genetics
  • Fimbriae, Bacterial* / metabolism
  • Gene Expression Regulation, Bacterial*
  • Operon
  • Promoter Regions, Genetic*
  • Vanillic Acid* / metabolism
  • Vanillic Acid* / pharmacology