TY - JOUR
T1 - 7,10-Epoxyoctadeca-7,9-dienoic Acid
T2 - A Small Molecule Adjuvant That Potentiates β-Lactam Antibiotics Against Multidrug-Resistant Staphylococcus aureus
AU - Dasagrandhi, Chakradhar
AU - Kim, Young Soon
AU - Kim, In Hwan
AU - Hou, Ching T.
AU - Kim, Hak Ryul
N1 - Funding Information:
Acknowledgements This research was supported by the Basic Science Research Program of the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, and future planning (2015R1A2A2A01005656).
Publisher Copyright:
© 2017, Association of Microbiologists of India.
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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 β-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 log10 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 β-lactam antibiotics against multidrug-resistant MRSA.
AB - 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 β-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 log10 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 β-lactam antibiotics against multidrug-resistant MRSA.
KW - 7,10-Epoxyoctadeca-7,9-dienoic acid
KW - Furan fatty acids
KW - Multidrug-resistant Staphylococcus aureus
KW - Synergistic antibacterial agent
KW - β-Lactam antibiotics
UR - http://www.scopus.com/inward/record.url?scp=85030862426&partnerID=8YFLogxK
U2 - 10.1007/s12088-017-0680-2
DO - 10.1007/s12088-017-0680-2
M3 - Article
AN - SCOPUS:85030862426
SN - 0046-8991
VL - 57
SP - 461
EP - 469
JO - Indian Journal of Microbiology
JF - Indian Journal of Microbiology
IS - 4
ER -