Antibiotic adjuvant activities of quorum sensing signal molecules DSF and BDSF against mature biofilms of Staphylococci

Among promising antibiofilm compounds, quorum-sensing (QS) molecules that regulate biological processes such as biofilm formation and intra- or interspecies communication appear to be good candidates. The invitro antibiotic-adjuvant effects of QS molecules diffusible signal factor (DSF) and B. cenocepacia producing-DSF (BDSF) were investigated against mature Staphylococcal biofilms. Broth microdilution methods were used for the determinations of MIC, MBC, MBIC, and MBEC, and bactericidal activities were determined by TKC method. The lowest MICs were obtained with ciprofloxacin and gentamicin, and MBECs with ciprofloxacin. DSF and BDSF at 0.5 µM decreased the MICs as 2–8, and 2–32 fold, respectively. In TKC studies, –cidal activities were achieved by BDSF + gentamycin, or ciprofloxacin, and DSF + daptomycin, vancomycin, meropenem or gentamycin combinations. Synergistic effects were generally obtained with BDSF + gentamicin combinations, followed by DSF + daptomycin against most S. aureus; while BDSF + gentamicin or ciprofloxacin, and DSF + vancomycin or meropenem were synergist against some S. epidermidis biofilms. Also, the antagonist effects were observed with BDSF + meropenem or ciprofloxacin against each MSSE and MSSA. It is estimated that these QS molecules, although it was strain dependent, generally enhanced the antibiotic activity, and would be a new and effective treatment strategy for biofilm control, either alone or as an antibiotic adjuvant.