title: Diffusible signal factor (DSF) quorum sensing signal and structurally related molecules enhance the antimicrobial efficacy of antibiotics against some bacterial pathogens.
abstract: BACKGROUND
  Extensive use of antibiotics has fostered the emergence of superbugs that are resistant to multidrugs, which becomes a great healthcare and public concern. Previous studies showed that quorum sensing signal DSF (diffusible signal factor) not only modulates bacterial antibiotic resistance through intraspecies signaling, but also affects bacterial antibiotic tolerance through interspecies communication. These findings motivate us to exploit the possibility of using DSF and its structurally related molecules as adjuvants to influence antibiotic susceptibility of bacterial pathogens.
  
  
  RESULTS
  In this study, we have demonstrated that DSF signal and its structurally related molecules could be used to induce bacterial antibiotic susceptibility. Exogenous addition of DSF signal (cis-11-methyl-2-dodecenoic acid) and its structural analogues could significantly increase the antibiotic susceptibility of Bacillus cereus, possibly through reducing drug-resistant activity, biofilm formation and bacterial fitness. The synergistic effect of DSF and its structurally related molecules with antibiotics on B. cereus is dosage-dependent. Combination of DSF with gentamicin showed an obviously synergistic effect on B. cereus pathogenicity in an in vitro model. We also found that DSF could increase the antibiotic susceptibility of other bacterial species, including Bacillus thuringiensis, Staphylococcus aureus, Mycobacterium smegmatis, Neisseria subflava and Pseudomonas aeruginosa.
  
  
  CONCLUSIONS
  The results indicate a promising potential of using DSF and its structurally related molecules as novel adjuvants to conventional antibiotics for treatment of infectious diseases caused by bacterial pathogens.
authors.forename: Yinyue
authors.initials: Y
authors.lastname: Deng
authors.forename: Amy
authors.initials: A
authors.lastname: Lim
authors.forename: Jasmine
authors.initials: J
authors.lastname: Lee
authors.forename: Shaohua
authors.initials: S
authors.lastname: Chen
authors.forename: Shuwen
authors.initials: S
authors.lastname: An
authors.forename: Yi-Hu
authors.initials: YH
authors.lastname: Dong
authors.affiliation: Institute of Molecular and Cell Biology, Proteos, 61 Biopolis Drive, Singapore 138673, Singapore. lianhui@imcb.a-star.edu.sg.
authors.forename: Lian-Hui
authors.initials: LH
authors.lastname: Zhang
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005839:Gentamicins / Q000494:pharmacology; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000502:physiology; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007850:Lauric Acids / Q000494:pharmacology*; D053038:Quorum Sensing
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins; D007850:Lauric Acids