Combination Therapy Using Low-Concentration Oxacillin with Palmitic Acid and Span85 to Control Clinical Methicillin-Resistant Staphylococcus aureus
- 주제(키워드) MRSA , drug combination therapy , palmitic acid , span85
- 주제(기타) Infectious Diseases
- 주제(기타) Pharmacology & Pharmacy
- 설명문(일반) [Song, Hun-Suk; Choi, Tae-Rim; Bhatia, Shashi Kant; Lee, Sun Mi; Park, Sol Lee; Lee, Hye Soo; Yang, Yung-Hun] Konkuk Univ, Dept Biol Engn, Coll Engn, Seoul 05029, South Korea; [Bhatia, Shashi Kant; Yang, Yung-Hun] Konkuk Univ, Inst Ubiquitous Informat Technol & Applicat CBRU, Seoul 05029, South Korea; [Kim, Yun-Gon] Soongsil Univ, Dept Chem Engn, 511 Sangdo Dong, Seoul 156743, South Korea; [Kim, Jae-Seok] Hallym Univ, Kangdong Sacred Heart Hosp, Dept Lab Med, Coll Med, Seoul 05355, South Korea; [Kim, Wooseong] Ewha Womans Univ, Coll Pharm, Seoul 03760, South Korea; [Kim, Wooseong] Ewha Womans Univ, Grad Sch Pharmaceut Sci, Seoul 03760, South Korea
- 등재 SCIE, SCOPUS
- OA유형 Green Published, gold
- 발행기관 MDPI
- 발행년도 2020
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000174675
- 본문언어 영어
- Published As http://dx.doi.org/10.3390/antibiotics9100682
- PubMed https://pubmed.ncbi.nlm.nih.gov/33049970
초록/요약
The overuse of antibiotics has led to the emergence of multidrug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA). MRSA is difficult to kill with a single antibiotic because it has evolved to be resistant to various antibiotics by increasing the PBP2a (mecA) expression level, building up biofilm, introducing SCCmec for multidrug resistance, and changing its membrane properties. Therefore, to overcome antibiotic resistance and decrease possible genetic mutations that can lead to the acquisition of higher antibiotic resistance, drug combination therapy was applied based on previous results indicating that MRSA shows increased susceptibility to free fatty acids and surfactants. The optimal ratio of three components and the synergistic effects of possible combinations were investigated. The combinations were directly applied to clinically isolated strains, and the combination containing 15 mu g/mL of oxacillin was able to control SCCmec type III and IV isolates having an oxacillin minimum inhibitory concentration (MIC) up to 1024 mu g/mL; moreover, the combination with a slightly increased oxacillin concentration was able to kill SCCmec type II. Phospholipid analysis revealed that clinical strains with higher resistance contained a high portion of 12-methyltetradecanoic acid (anteiso-C15:0) and 14-methylhexadecanoic acid (anteiso-C17:0), although individual strains showed different patterns. In summary, we showed that combinatorial therapy with a low concentration of oxacillin controlled different laboratory and highly diversified clinical MRSA strains.
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