7,10-Epoxyoctadeca-7,9-dienoic Acid: A Small Molecule Adjuvant That Potentiates beta-Lactam Antibiotics Against Multidrug-Resistant Staphylococcus aureus

초록

The emergence of methicillin-resistant Staphylococcus aureus (MRSA) infections with multi-drug resistance needs effective and alternative control strategies. In this study we investigated the adjuvant effect of a novel furan fatty acid, 7,10-epoxyoctadeca-7,9-dienoic acid (7,10-EODA) against multidrug-resistant S. aureus (MDRSA) strain 01ST001 by disc diffusion, checker board and time kill assays. Further the membrane targeting action of 7,10-EODA was investigated by spectroscopic and confocal microscopic studies. 7,10-EODA exerted synergistic activity along with beta-lactam antibiotics against all clinical MRSA strains, with a mean fractional inhibitory concentration index below 0.5. In time-kill kinetic study, combination of 7,10-EODA with oxacillin, ampicillin, and penicillin resulted in 3.8-4.2 log(10) reduction in the viable counts of MDRSA 01ST001. Further, 7,10-EODA dose dependently altered the membrane integrity (p < 0.001) and increased the binding of fluorescent analog of penicillin, Bocillin-FL to the MDRSA cells. The membrane action of 7,10-EODA further facilitated the uptake of several other antibiotics in MDRSA. The results of the present study suggested that 7,10-EODA could be a novel antibiotic adjuvant, especially useful in repurposing beta-lactam antibiotics against multidrug-resistant MRSA.

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