Farnesol increases the susceptibility of Burkholderia pseudomallei biofilm to antimicrobials used to treat melioidosis

J Appl Microbiol. 2016 Mar;120(3):600-6. doi: 10.1111/jam.13027.

Abstract

Aims: The aim of this study was to analyse the in vitro activity of farnesol alone and combined with the antibacterial drugs amoxicillin, doxycycline, ceftazidime and sulfamethoxazole-trimethoprim against Burkholderia pseudomallei biofilms.

Methods and results: Susceptibility was assessed by the broth microdilution test and cell viability was read with the oxidation-reduction indicator dye resazurin. The biofilms were evaluated through three microscopic techniques (optical, confocal and electronic microscopy). The minimum biofilm erradication concentration (MBEC) for farnesol was 75-2400 mmol l(-1). In addition, farnesol significantly reduced the MBEC values for ceftazidime, amoxicillin, doxycycline and sulfamethoxazole-trimethoprim by 256, 16, 4 and 4 times respectively (P < 0·05). Optical, confocal and electronic microscopic analyses of farnesol-treated B. pseudomallei biofilms demonstrated that this compound damages biofilm matrix, probably facilitating antimicrobial penetration in the biofilm structure.

Conclusions: This study demonstrated the effectiveness of farnesol against B. pseudomallei biofilms and its potentiating effect on the activity of antibacterial drugs, in particular ceftazidime, amoxicillin, doxycycline and sulfamethoxazole-trimethoprim.

Significance and impact of the study: The intrinsic antimicrobial resistance of B. pseudomallei is a serious challenge for the treatment of melioidosis. Thus, this paper reports the inhibitory potential of farnesol against B. pseudomallei biofilms, as well as highlights the favourable pharmacological interaction of farnesol with antibiotics tested, not only on cell viability, but also in the structural morphology of biofilms.

Keywords: Burkholderia pseudomallei; biofilm; farnesol; melioidosis; susceptibility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amoxicillin / pharmacology
  • Anti-Bacterial Agents / pharmacology
  • Biofilms / drug effects*
  • Burkholderia pseudomallei / drug effects*
  • Burkholderia pseudomallei / physiology
  • Ceftazidime / pharmacology
  • Farnesol / pharmacology*
  • Humans
  • Melioidosis / drug therapy
  • Melioidosis / microbiology*
  • Microbial Sensitivity Tests / methods
  • Trimethoprim, Sulfamethoxazole Drug Combination

Substances

  • Anti-Bacterial Agents
  • Farnesol
  • Amoxicillin
  • Trimethoprim, Sulfamethoxazole Drug Combination
  • Ceftazidime