聚六亚甲基双胍对细胞内金黄色葡萄球菌EMRSA - 15和USA 300的杀菌作用。
Bactericidal effects of polyhexamethylene biguanide against intracellular Staphylococcus aureus EMRSA-15 and USA 300.
作者信息
Kamaruzzaman Nor Fadhilah, Firdessa Rebuma, Good Liam
机构信息
Department of Pathology and Pathogen Biology, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK Faculty of Veterinary Medicine, Universiti Malaysia Kelantan, Locked Bag 36, Pengkalan Chepa, 16100 Kota Bharu, Kelantan, Malaysia.
Institute for Molecular Infection Biology, Josef-Schneider-Str. 2/D15, University of Würzburg, 97080 Würzburg, Germany.
出版信息
J Antimicrob Chemother. 2016 May;71(5):1252-9. doi: 10.1093/jac/dkv474. Epub 2016 Jan 28.
OBJECTIVES
The treatment of skin infections caused by Staphylococcus aureus is limited by acquired antibiotic resistance and poor drug delivery into pathogen and host cells. Here, we investigated the antibacterial activities of six topically used antimicrobials and a cationic polymer, polyhexamethylene biguanide (PHMB), against intracellular MSSA strain RN4420 and MRSA strains EMRSA-15 and USA 300.
METHODS
The MICs of antimicrobials were determined for MSSA and MRSA strains, and the bactericidal activities of nadifloxacin and PHMB against intracellular MRSA were determined using infected keratinocytes. Fluorescein-tagged PHMB (PHMB-FITC) was used to study PHMB uptake, co-localization with intracellular EMRSA-15 and retention in keratinocytes. The mechanism(s) of PHMB uptake into keratinocytes were studied using a dynamin inhibitor, dynasore.
RESULTS
Gentamicin, nadifloxacin and PHMB showed the lowest MICs for MRSA. Nadifloxacin at 10 mg/L killed 80% of intracellular EMRSA-15, but was not effective against USA 300. PHMB at 4 mg/L killed almost 100% of intracellular EMRSA-15 and USA 300. PHMB entered keratinocytes, co-localized with intracellular EMRSA-15 and was retained by the cells for over 5 h. PHMB uptake and its intracellular antibacterial activities were inhibited by the dynamin inhibitor, dynasore.
CONCLUSIONS
PHMB kills intracellular MRSA via direct interaction with pathogens inside keratinocytes and host cell entry is dynamin dependent.
目的
金黄色葡萄球菌引起的皮肤感染治疗受到获得性抗生素耐药性以及药物进入病原体和宿主细胞能力差的限制。在此，我们研究了六种局部使用的抗菌剂和一种阳离子聚合物聚六亚甲基双胍（PHMB）对细胞内甲氧西林敏感金黄色葡萄球菌菌株RN4420以及耐甲氧西林金黄色葡萄球菌菌株EMRSA - 15和USA 300的抗菌活性。
方法
测定了抗菌剂对甲氧西林敏感金黄色葡萄球菌和耐甲氧西林金黄色葡萄球菌菌株的最低抑菌浓度（MIC），并使用感染的角质形成细胞测定了萘啶酸和PHMB对细胞内耐甲氧西林金黄色葡萄球菌的杀菌活性。用荧光素标记的PHMB（PHMB - FITC）研究PHMB的摄取、与细胞内EMRSA - 15的共定位以及在角质形成细胞中的保留情况。使用发动蛋白抑制剂dynasore研究PHMB进入角质形成细胞的机制。
结果
庆大霉素、萘啶酸和PHMB对耐甲氧西林金黄色葡萄球菌显示出最低的最低抑菌浓度。10 mg/L的萘啶酸杀死了80%的细胞内EMRSA - 15，但对USA 300无效。4 mg/L的PHMB杀死了几乎100%的细胞内EMRSA - 15和USA 300。PHMB进入角质形成细胞，与细胞内EMRSA - 15共定位，并在细胞内保留超过5小时。发动蛋白抑制剂dynasore抑制了PHMB的摄取及其细胞内抗菌活性。
结论
PHMB通过与角质形成细胞内的病原体直接相互作用杀死细胞内耐甲氧西林金黄色葡萄球菌，并且进入宿主细胞依赖发动蛋白。
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