Sulfonamide-based diffusible signal factor analogs interfere with quorum sensing in Stenotrophomonas maltophilia and Burkholderia cepacia

Pol Huedo, Vydyula P. Kumar, Conor Horgan, Daniel Yero, Xavier Daura, Isidre Gibert, Timothy P. O'sullivan

Research output: Contribution to journalArticleResearch

1 Citation (Scopus)

Abstract

© 2019 Newlands Press. Aim: Stenotrophomonas maltophilia (Sm) and Burkholderia cepacia complex (BCC) are Gram-negative bacterial pathogens, which are typically multidrug resistant and excellent biofilm producers. These phenotypes are controlled by quorum sensing (QS) systems from the diffusible signal factor (DSF) family. We aim to interfere with this QS system as an alternative approach in combatting such difficult-to-treat infections. Materials & methods: A library of sulfonamide-based DSF bioisosteres was synthesized and tested against the major phenotypes regulated by QS. Results & conclusion: Several analogs display significant antibiofilm activity while the majority increase the action of the last-resort antibiotic colistin against Sm and BCC. Most compounds inhibit DSF synthesis in the Sm K279a strain. Our results support the strategy of interfering with QS communications to combat multidrug resistance.
Original languageEnglish
Pages (from-to)1565-1582
JournalFuture Medicinal Chemistry
Volume11
DOIs
Publication statusPublished - 1 Jan 2019

Keywords

  • antimicrobials
  • biofilms
  • bioisosterism
  • Burkholderia cepacia complex
  • multidrug resistance
  • nosocomial pathogens
  • QS inhibitors
  • quorum sensing (QS)
  • Stenotrophomonas maltophilia
  • sulfonamides

Fingerprint Dive into the research topics of 'Sulfonamide-based diffusible signal factor analogs interfere with quorum sensing in Stenotrophomonas maltophilia and Burkholderia cepacia'. Together they form a unique fingerprint.

Cite this