Controlling persister cells of Pseudomonas aeruginosa PDO300 by (Z)-4-bromo-5-(bromomethylene)-3-methylfuran-2(5H)-one

Jiachuan Pan, Fangchao Song, Dacheng Ren

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Pseudomonas aeruginosa is a major pathogen causing chronic pulmonary infections; for example, 80% of cystic fibrosis patients get infected by this bacterium as the disease progresses. Such chronic infections are challenging because P. aeruginosa exhibits high-level tolerance to antibiotics by forming biofilms (multicellular structures attached to surfaces), by entering dormancy and forming antibiotic tolerant persister cells, and by conversion to the mucoid phenotype. Recently, we reported that a synthetic quorum sensing inhibitor, (Z)-4-bromo-5-(bromomethylene)-3-methylfuran-2(5H)-one (BF8), can sensitize both planktonic and biofilm-associated persister cells of P. aeruginosa PAO1 to antibiotics at the concentrations non-inhibitory to its growth. In this study, we further characterized the effects of this compound on the mucoid strain P. aeruginosa PDO300. BF8 was found to reduce persistence during the growth of PDO300 and effectively kill the persister cells isolated from PDO300 cultures. In addition to planktonic cells, BF8 was also found to inhibit biofilm formation of PDO300 and reduce associated persistence. These findings broaden the activities of this class of compounds and indicate that BF8 also has other targets in P. aeruginosa in addition to quorum sensing.

Original languageEnglish (US)
Pages (from-to)4648-4651
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume23
Issue number16
DOIs
StatePublished - Aug 15 2013

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Keywords

  • Antibiotic tolerance
  • Biofilm
  • Mucoid
  • Persister
  • Pseudomonas aeruginosa
  • Quorum sensing

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

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