Bis-(3'-5')-cyclic dimeric GMP regulates antimicrobial peptide resistance in Pseudomonas aeruginosa

Antimicrob Agents Chemother. 2013 May;57(5):2066-75. doi: 10.1128/AAC.02499-12. Epub 2013 Feb 12.

Abstract

Bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) is an intracellular second messenger that controls the lifestyles of many bacteria. A high intracellular level of c-di-GMP induces a biofilm lifestyle, whereas a low intracellular level of c-di-GMP stimulates dispersal of biofilms and promotes a planktonic lifestyle. Here, we used the expression of different reporters to show that planktonic cells, biofilm cells, and cells dispersed from biofilms (DCells) had distinct intracellular c-di-GMP levels. Proteomics analysis showed that the low intracellular c-di-GMP level of DCells induced the expression of proteins required for the virulence and development of antimicrobial peptide resistance in Pseudomonas aeruginosa. In accordance with this, P. aeruginosa cells with low c-di-GMP levels were found to be more resistant to colistin than P. aeruginosa cells with high c-di-GMP levels. This finding contradicts the current dogma stating that dispersed cells are inevitably more susceptible to antibiotics than their sessile counterparts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism
  • Biofilms / drug effects
  • Biofilms / growth & development
  • Colistin / pharmacology*
  • Cyclic GMP / analogs & derivatives*
  • Cyclic GMP / metabolism
  • Drug Resistance, Bacterial / drug effects*
  • Drug Resistance, Bacterial / genetics
  • Gene Expression Profiling
  • Gene Expression Regulation, Bacterial / drug effects*
  • Genes, Reporter
  • Green Fluorescent Proteins
  • Plankton / drug effects
  • Plankton / growth & development
  • Proteomics
  • Pseudomonas aeruginosa / drug effects
  • Pseudomonas aeruginosa / genetics*
  • Pseudomonas aeruginosa / metabolism
  • Second Messenger Systems / genetics*

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Green Fluorescent Proteins
  • bis(3',5')-cyclic diguanylic acid
  • Cyclic GMP
  • Colistin