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Abstract：
BACKGROUND: A major worldwide health issue is the rising frequency of resistance of bacteria.Drug combinations are a winning strategy in fighting resistant bacteria and might help in protecting the existing drugs.Monolaurin is natural compound extracted from coconut oil and has a promising antimicrobial activity against Staphylococcus.aureus. This study aims to examine the efficacy of monolaurin both individually and in combination with β-lactam antibiotics against Staphylococcus aureus isolates.
METHODS: Agar dilution method was used for determination of minimum inhibitory concentration (MIC) of monolaurin against S.aureus isolates. Scanning electron microscope (SEM) was used to detect morphological changes in S.aureus after treatment with monolaurin. Conventional and Real-time Polymerase chain reaction (RT-PCR) were performed to detect of beta-lactamase (blaZ) gene and its expressional levels after monolaurin treatment. Combination therapy of monolaurin and antibiotics was assessed through fractional inhibitory concentration and time-kill method.
RESULTS: The antibacterial activity of monolaurin was assessed on 115 S.aureus isolates, the MIC of monolaurin were 250 to 2000 µg/ml. SEM showed cell elongation and swelling in the outer membrane of S.aureus in the prescence of 1xMIC of monolaurin. blaZ gene was found in 73.9% of S.aureus isolates. RT-PCR shows a significant decrease in of blaZ gene expression at 250 and 500 µg/ml of monolaurin. Synergistic effects were detected through FIC method and time killing curve. Combination therapy established a significant reduction on the MIC value. The collective findings from the antibiotic combinations with monolaurin indicated synergism rates ranging from 83.3% to 100%.In time-kill studies, combination of monolaurin and β-lactam antibiotics produced a synergistic effect.
CONCLUSIONS: This study showed that monolaurin may be a natural antibacterial agent against S. aureus, and may be an outstanding modulator of β-lactam drugs. The concurrent application of monolaurin and β-lactam antibiotics, exhibiting synergistic effects against S. aureus in vitro, holds promise as potential candidates for the development of combination therapies that target particularly, patients with bacterial infections that are nearly incurable.
METHODS: Agar dilution method was used for determination of minimum inhibitory concentration (MIC) of monolaurin against S.aureus isolates. Scanning electron microscope (SEM) was used to detect morphological changes in S.aureus after treatment with monolaurin. Conventional and Real-time Polymerase chain reaction (RT-PCR) were performed to detect of beta-lactamase (blaZ) gene and its expressional levels after monolaurin treatment. Combination therapy of monolaurin and antibiotics was assessed through fractional inhibitory concentration and time-kill method.
RESULTS: The antibacterial activity of monolaurin was assessed on 115 S.aureus isolates, the MIC of monolaurin were 250 to 2000 µg/ml. SEM showed cell elongation and swelling in the outer membrane of S.aureus in the prescence of 1xMIC of monolaurin. blaZ gene was found in 73.9% of S.aureus isolates. RT-PCR shows a significant decrease in of blaZ gene expression at 250 and 500 µg/ml of monolaurin. Synergistic effects were detected through FIC method and time killing curve. Combination therapy established a significant reduction on the MIC value. The collective findings from the antibiotic combinations with monolaurin indicated synergism rates ranging from 83.3% to 100%.In time-kill studies, combination of monolaurin and β-lactam antibiotics produced a synergistic effect.
CONCLUSIONS: This study showed that monolaurin may be a natural antibacterial agent against S. aureus, and may be an outstanding modulator of β-lactam drugs. The concurrent application of monolaurin and β-lactam antibiotics, exhibiting synergistic effects against S. aureus in vitro, holds promise as potential candidates for the development of combination therapies that target particularly, patients with bacterial infections that are nearly incurable.
摘要：
背景：全球主要的健康问题是细菌耐药性的上升频率。药物组合是对抗耐药细菌的成功策略，可能有助于保护现有药物。单月桂酯是从椰子油中提取的天然化合物，对葡萄球菌具有良好的抗菌活性。金黄色葡萄球菌。这项研究旨在检查单月桂酸酯单独或与β-内酰胺抗生素联合使用对金黄色葡萄球菌分离株的功效。
方法：采用琼脂稀释法测定单月桂酸酯对金黄色葡萄球菌的最低抑菌浓度(MIC)。用扫描电子显微镜(SEM)检测单月桂酸酯处理后金黄色葡萄球菌的形态变化。进行常规和实时聚合酶链反应（RT-PCR）以检测单月桂酸酯处理后的β-内酰胺酶（blaZ）基因及其表达水平。单月桂酸酯和抗生素的联合治疗通过部分抑制浓度和时间杀伤方法进行评估。
结果：对115株金黄色葡萄球菌进行了单月桂酸的抗菌活性评估，单月桂酸的MIC为250至2000微克/毫升。SEM显示在存在1xMIC的monolaurin的情况下，金黄色葡萄球菌的外膜中的细胞伸长和溶胀。blaZ基因在金黄色葡萄球菌分离株的73.9%中被发现。RT-PCR显示250和500μg/ml单脂菌素时blaZ基因表达显着降低。通过FIC方法和时间杀伤曲线检测协同作用。联合治疗建立了MIC值的显著降低。抗生素与monolaurin的组合的集体发现表明协同率为83.3％至100％。在消磨时间的研究中，单月桂酸酯和β-内酰胺抗生素的组合产生了协同作用。
结论：这项研究表明，单月桂酸酯可能是一种抗金黄色葡萄球菌的天然抗菌剂，并且可能是β-内酰胺药物的杰出调节剂。单月桂酸酯和β-内酰胺类抗生素的同时应用，在体外对金黄色葡萄球菌表现出协同作用，有望成为开发特别针对的联合疗法的潜在候选人，几乎无法治愈的细菌感染患者。
方法：采用琼脂稀释法测定单月桂酸酯对金黄色葡萄球菌的最低抑菌浓度(MIC)。用扫描电子显微镜(SEM)检测单月桂酸酯处理后金黄色葡萄球菌的形态变化。进行常规和实时聚合酶链反应（RT-PCR）以检测单月桂酸酯处理后的β-内酰胺酶（blaZ）基因及其表达水平。单月桂酸酯和抗生素的联合治疗通过部分抑制浓度和时间杀伤方法进行评估。
结果：对115株金黄色葡萄球菌进行了单月桂酸的抗菌活性评估，单月桂酸的MIC为250至2000微克/毫升。SEM显示在存在1xMIC的monolaurin的情况下，金黄色葡萄球菌的外膜中的细胞伸长和溶胀。blaZ基因在金黄色葡萄球菌分离株的73.9%中被发现。RT-PCR显示250和500μg/ml单脂菌素时blaZ基因表达显着降低。通过FIC方法和时间杀伤曲线检测协同作用。联合治疗建立了MIC值的显著降低。抗生素与monolaurin的组合的集体发现表明协同率为83.3％至100％。在消磨时间的研究中，单月桂酸酯和β-内酰胺抗生素的组合产生了协同作用。
结论：这项研究表明，单月桂酸酯可能是一种抗金黄色葡萄球菌的天然抗菌剂，并且可能是β-内酰胺药物的杰出调节剂。单月桂酸酯和β-内酰胺类抗生素的同时应用，在体外对金黄色葡萄球菌表现出协同作用，有望成为开发特别针对的联合疗法的潜在候选人，几乎无法治愈的细菌感染患者。
