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5-Benzylidene-4-oxazolidinones potently inhibit biofilm formation in Methicillin-resistant Staphylococcus aureus.

ABSTRACT: Investigation into the biological function of 5-benzylidene-4-oxazolidinones revealed dose-dependent inhibition of biofilm formation in Methicillin-resistant S. aureus (MRSA). This structurally unusual class of small molecules inhibit up to 89% of biofilm formation with IC50 values as low as 0.78 ?M, and disperse pre-formed biofilms with IC50 values as low as 4.7 ?M. Together, these results suggest that 4-oxazolidinones represent new chemotypes to enable the study of bacterial biofilms with small molecule chemical probes.

SUBMITTER: Edwards GA

PROVIDER: S-EPMC5526077 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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5-Benzylidene-4-oxazolidinones potently inhibit biofilm formation in Methicillin-resistant Staphylococcus aureus.

Edwards Grant A GA Shymanska Nataliia V NV Pierce Joshua G JG

Chemical communications (Cambridge, England) 20170601 53

Investigation into the biological function of 5-benzylidene-4-oxazolidinones revealed dose-dependent inhibition of biofilm formation in Methicillin-resistant S. aureus (MRSA). This structurally unusual class of small molecules inhibit up to 89% of biofilm formation with IC<sub>50</sub> values as low as 0.78 μM, and disperse pre-formed biofilms with IC<sub>50</sub> values as low as 4.7 μM. Together, these results suggest that 4-oxazolidinones represent new chemotypes to enable the study of bacter ...[more]

PMID: 28537316

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Project description:ObjectivesEpidemic methicillin-resistant S. aureus (MRSA) clones cause infections in both hospital and community settings. As a biofilm phenotype further facilitates evasion of the host immune system and antibiotics, we compared the biofilm-forming capacities of various MRSA clones.MethodsSeventy-six MRSA classified into 13 clones (USA300, EMRSA-15, Hungarian/Brazilian etc.), and isolated from infections or from carriers were studied for biofilm formation under static and dynamic conditions. Static biofilms in microtitre plates were quantified colorimetrically. Dynamic biofilms (Bioflux 200, Fluxion, USA) were studied by confocal laser-scanning and time-lapse microscopy, and the total volume occupied by live/dead bacteria quantified by Volocity 5.4.1 (Improvision, UK).ResultsMRSA harbouring SCCmec IV produced significantly more biomass under static conditions than SCCmec I-III (P = 0.003), and those harbouring SCCmec II significantly less than those harbouring SCCmec I or III (P<0.001). In the dynamic model, SCCmec I-III harbouring MRSA were significantly better biofilm formers than SCCmec IV (P = 0.036). Only 16 strains successfully formed biofilms under both conditions, of which 13 harboured SCCmec IV and included all tested USA300 strains (n = 3). However, USA300 demonstrated remarkably lower percentages of cell-occupied space (6.6%) compared to the other clones (EMRSA-15 = 19.0%) under dynamic conditions. Time-lapse microscopy of dynamic biofilms demonstrated that USA300 formed long viscoelastic tethers that stretched far from the point of attachment, while EMRSA-15 consisted of micro-colonies attached densely to the surface.ConclusionsMRSA harbouring SCCmec types IV and I-III demonstrate distinct biofilm forming capacities, possibly owing to their adaptation to the community and hospital settings, respectively. USA300 demonstrated abundant biofilm formation under both conditions, which probably confers a competitive advantage, contributing to its remarkable success as a pathogen.

Dataset Information

5-Benzylidene-4-oxazolidinones potently inhibit biofilm formation in Methicillin-resistant Staphylococcus aureus.

Publications

5-Benzylidene-4-oxazolidinones potently inhibit biofilm formation in Methicillin-resistant Staphylococcus aureus.

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