Miyazaki Haruko, Midorikawa Naoko, Fujimoto Saki, Miyoshi Natsumi, Yoshida Hideto, Matsumoto Tetsuya
Department of Microbiology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan.
Department of Microbiology, Tokyo Medical University, Tokyo, Japan.
Ther Adv Infect Dis. 2017 Jul;4(4):89-94. doi: 10.1177/2049936117714920. Epub 2017 Jul 5.
Methicillin-resistant (MRSA) is an important health care-associated and community-associated pathogen and causes a large number of infections worldwide. For the purpose of application to topical treatment of MRSA infection, we examined the antimicrobial effects of lysophosphatidylcholine (LPC) on MRSA strains. We also investigated the combination effect of LPC and gentamicin on MRSA growth.
The LPC minimum inhibitory concentrations (MIC) for Gram-positive (, and ) and Gram-negative (, and ) bacteria were measured by the broth microdilution method. The mechanism of LPC-mediated MRSA killing was investigated by membrane permeability analysis with DiSC3(5) fluorescence and growth curve analysis. Lastly, the effects of LPC on gentamicin-induced bactericidal activity were determined in combination treatment studies with 15 gentamicin-resistant MRSA isolates from the skin, nose, or ears.
The LPC MIC for Gram-positive bacteria varied between 32 µg/ml and >2048 µg/ml, whereas that for all Gram-negative bacteria was >2048 µg/ml. Consistently, membrane permeability analysis showed that LPC was substantially more effective in inducing membrane permeability in Gram-positive bacteria than in Gram-negative counterparts. Growth curve analysis in cotreatment studies demonstrated that LPC has intrinsic bactericidal effects and can also potentiate gentamicin sensitivity in resistant MRSA strains.
Our study demonstrates that LPC exhibits intrinsic antimicrobial effects and can enhance the antimicrobial effects of gentamicin for resistant MRSA strains, suggesting that LPC may be a beneficial additive in topical antibiotics for superficial skin infections.
耐甲氧西林金黄色葡萄球菌（MRSA）是一种重要的医疗保健相关和社区相关病原体，在全球范围内引起大量感染。为了将其应用于MRSA感染的局部治疗，我们研究了溶血磷脂酰胆碱（LPC）对MRSA菌株的抗菌作用。我们还研究了LPC与庆大霉素联合对MRSA生长的影响。
采用肉汤微量稀释法测定LPC对革兰氏阳性菌（ 、 和 ）和革兰氏阴性菌（ 、 和 ）的最低抑菌浓度（MIC）。通过DiSC3(5)荧光膜通透性分析和生长曲线分析研究LPC介导的MRSA杀伤机制。最后，在与15株来自皮肤、鼻子或耳朵的耐庆大霉素MRSA分离株的联合治疗研究中，确定LPC对庆大霉素诱导的杀菌活性的影响。
LPC对革兰氏阳性菌的MIC在32μg/ml至>2048μg/ml之间，而对所有革兰氏阴性菌的MIC均>2048μg/ml。一致地，膜通透性分析表明，LPC在诱导革兰氏阳性菌膜通透性方面比革兰氏阴性菌更有效。联合治疗研究中的生长曲线分析表明，LPC具有内在的杀菌作用，还可以增强耐药MRSA菌株对庆大霉素的敏感性。
我们的研究表明，LPC具有内在的抗菌作用，可以增强庆大霉素对耐药MRSA菌株的抗菌作用，这表明LPC可能是浅表皮肤感染局部抗生素中的有益添加剂。
