| Autor: |
Sharafutdinov IS; Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia., Trizna EY; Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia., Baidamshina DR; Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia., Ryzhikova MN; Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia., Sibgatullina RR; Biofunctional Chemistry Laboratory, Alexander Butlerov Institute of Chemistry, Kazan Federal University, Kazan, Russia., Khabibrakhmanova AM; Biofunctional Chemistry Laboratory, Alexander Butlerov Institute of Chemistry, Kazan Federal University, Kazan, Russia., Latypova LZ; Biofunctional Chemistry Laboratory, Alexander Butlerov Institute of Chemistry, Kazan Federal University, Kazan, Russia., Kurbangalieva AR; Biofunctional Chemistry Laboratory, Alexander Butlerov Institute of Chemistry, Kazan Federal University, Kazan, Russia., Rozhina EV; Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia., Klinger-Strobel M; Center for Infectious Diseases and Infection Control, Jena University Hospital, Jena, Germany., Fakhrullin RF; Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia., Pletz MW; Center for Infectious Diseases and Infection Control, Jena University Hospital, Jena, Germany., Bogachev MI; Biomedical Engineering Research Centre, Saint Petersburg Electrotechnical University, Saint Petersburg, Russia., Kayumov AR; Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia., Makarewicz O; Center for Infectious Diseases and Infection Control, Jena University Hospital, Jena, Germany. |
| Abstrakt: |
The gram-positive opportunistic bacterium Staphylococcus aureus is one of the most common causatives of a variety of diseases including skin and skin structure infection or nosocomial catheter-associated infections. The biofilm formation that is an important virulence factor of this microorganism renders the antibiotic therapy ineffective, because biofilm-embedded bacteria exhibit strongly increased tolerance to antimicrobials. Here, we describe a novel 3-chloro-5( S )-[(1 R ,2 S ,5 R )-2-isopropyl-5-methylcyclohexyloxy]-4-[4-methylphenylsulfonyl]-2(5 H )-furanone ( F105 ), possessing a sulfonyl group and l -menthol moiety. Minimal inhibitory and bactericidal concentration values (MIC and MBC) of F105 were 10 and 40 mg/L, respectively, suggesting F105 biocidal properties. F105 exhibits pronounced activity against biofilm-embedded S. aureus and increases the efficacy of aminoglycosides (amikacin, gentamicin, and kanamycin) and benzalkonium chloride with fractional inhibitory concentration index values of 0.33-0.44 and 0.29, respectively, suggesting an alternative external treatment option, e.g., for wound infections. Moreover, low concentrations (0.5-1.3 mg/L) of F105 reduced the MICs of these antimicrobials twofold. By using confocal laser scanning microscopy and CFU counting, we show explicitly that F105 also restores the antimicrobial activity of gentamicin and ampicillin against S. aureus biofilms by several orders of magnitude. Biofilm structures were not destroyed but sterilized, with embedded cells being almost completely killed at twofold MBC. While F105 is quite toxic (CC 50 /MBC ratio 0.2), our data suggest that the F105 chemotype might be a promising starting point for the development of complex topical agents for combined anti-staphylococcal biofilm-therapies restoring the efficacy of some antibiotics against difficult to treat S. aureus biofilm. |
