A Genetic Basis for Pseudomonas Aeruginosa Biofilm Antibiotic Resistance

Nature. 2003 Nov 20;426(6964):306-10. doi: 10.1038/nature02122.

Abstract

Biofilms are surface-attached microbial communities with characteristic architecture and phenotypic and biochemical properties distinct from their free-swimming, planktonic counterparts. One of the best-known of these biofilm-specific properties is the development of antibiotic resistance that can be up to 1,000-fold greater than planktonic cells. We report a genetic determinant of this high-level resistance in the Gram-negative opportunistic pathogen, Pseudomonas aeruginosa. We have identified a mutant of P. aeruginosa that, while still capable of forming biofilms with the characteristic P. aeruginosa architecture, does not develop high-level biofilm-specific resistance to three different classes of antibiotics. The locus identified in our screen, ndvB, is required for the synthesis of periplasmic glucans. Our discovery that these periplasmic glucans interact physically with tobramycin suggests that these glucose polymers may prevent antibiotics from reaching their sites of action by sequestering these antimicrobial agents in the periplasm. Our results indicate that biofilms themselves are not simply a diffusion barrier to these antibiotics, but rather that bacteria within these microbial communities employ distinct mechanisms to resist the action of antimicrobial agents.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Biofilms / drug effects*
  • Biofilms / growth & development
  • Drug Resistance, Bacterial*
  • Glucans / biosynthesis
  • Glucans / metabolism
  • Microbial Sensitivity Tests
  • Mutation
  • Periplasm / metabolism
  • Phenotype
  • Plankton
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / genetics*
  • Pseudomonas aeruginosa / physiology

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Glucans