Reverting antibiotic tolerance of Pseudomonas aeruginosa PAO1 persister cells by (Z)-4-bromo-5-(bromomethylene)-3-methylfuran-2(5H)-one

• Published in: PloS one 2012-09, Vol.7 (9), p.e45778
• Main Authors: Pan, Jiachuan, Bahar, Ali Adem, Syed, Haseeba, Ren, Dacheng
• Format: Article
• Language: English
• Subjects: 4-Butyrolactone - analogs & derivatives; 4-Butyrolactone - pharmacology; Analysis of Variance; Anti-Bacterial Agents - pharmacology; Antibiotic tolerance; Antibiotics; Antimicrobial agents; Bacteria; Bacterial infections; Biofilms; Biofilms - drug effects; Biology; Biomedical materials; Carbenicillin - pharmacology; Chemical engineering; Chemistry; Ciprofloxacin - pharmacology; Control methods; Drug resistance; Drug Resistance, Bacterial; Drug Synergism; E coli; Escherichia coli; Genes, Bacterial; Gentamicins - pharmacology; Gram-negative bacteria; Infections; Laboratories; Medicine; Microbial Sensitivity Tests; Multidrug resistance; Oligonucleotide Array Sequence Analysis; Pseudomonas aeruginosa; Pseudomonas aeruginosa - cytology; Pseudomonas aeruginosa - drug effects; Pseudomonas aeruginosa - metabolism; Pseudomonas aeruginosa - physiology; Quorum Sensing - drug effects; Staphylococcus aureus; Tetracycline - pharmacology; Tobramycin - pharmacology; Transcriptome - drug effects; Tuberculosis
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0045778

Bacteria are well known to form dormant persister cells that are tolerant to most antibiotics. Such intrinsic tolerance also facilitates the development of multidrug resistance through acquired mechanisms. Thus persister cells are a promising target for developing more effective methods to control chronic infections and help prevent the development of multidrug-resistant bacteria. However, control of persister cells is still an unmet challenge. We show in this report that (Z)-4-bromo-5-(bromomethylene)-3-methylfuran-2(5H)-one (BF8) can restore the antibiotic susceptibility of Pseudomonas aeruginosa PAO1 persister cells at growth non-inhibitory concentrations. Persister control by BF8 was found to be effective against both planktonic and biofilm cells of P. aeruginosa PAO1. Interestingly, although BF8 is an inhibitor of quorum sensing (QS) in Gram-negative bacteria, the data in this study suggest that the activities of BF8 to revert antibiotic tolerance of P. aeruginosa PAO1 persister cells is not through QS inhibition and may involve other targets. BF8 can sensitize P. aeruginosa persister cells to antibiotics.