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抗菌肽乳酸链球菌素Z与传统抗生素的相互作用以及使用纳米结构脂质载体增强抗菌活性

Interactions of the antimicrobial peptide nisin Z with conventional antibiotics and the use of nanostructured lipid carriers to enhance antimicrobial activity.

作者信息

Lewies Angélique, Wentzel Johannes Frederik, Jordaan Anine, Bezuidenhout Carlos, Du Plessis Lissinda Hester

机构信息

Centre of Excellence for Pharmaceutical Sciences (PHARMACEN), North-West University, Potchefstroom, 2520, South Africa.

Centre of Excellence for Pharmaceutical Sciences (PHARMACEN), North-West University, Potchefstroom, 2520, South Africa.

出版信息

Int J Pharm. 2017 Jun 30;526(1-2):244-253. doi: 10.1016/j.ijpharm.2017.04.071. Epub 2017 Apr 29.

DOI:10.1016/j.ijpharm.2017.04.071
PMID:28461263
Abstract

Antimicrobial resistance is an imminent threat to the effective prevention and treatment of bacterial infections and alternative antimicrobial strategies are desperately needed. Antimicrobial peptides (AMPs) may be promising alternatives to current antibiotics or act as adjuvants to enhance antibiotic potency. Additionally, the use of biodegradable lipid nanoparticles can enhance the antibacterial activity of antibiotics and antimicrobial peptides. In this study, the interaction of the AMPs, nisin Z and melittin, with conventional antibiotics was investigated on Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli. The effectiveness of nanostructured lipid carriers (NLCs) for the entrapment of nisin Z was also evaluated. Findings revealed that nisin Z exhibited additive interactions with numerous conventional antibiotics. Notable synergism was observed for novobiocin-nisin Z combinations. The addition of the non-antibiotic adjuvant EDTA significantly improved the antimicrobial activity of free nisin Z towards E.coli. NLCs containing nisin Z were effective against Gram-positive species at physiological pH, with an increase in effectiveness in the presence of EDTA. Results indicate that nisin Z may be advantageous as an adjuvant in antimicrobial chemotherapy, while contributing in the battle against antibiotic resistance. NLCs have the potential to enhance the antibacterial activity of nisin Z towards Gram-positive bacterial species associated with skin infections.

摘要

抗生素耐药性是有效预防和治疗细菌感染的紧迫威胁,因此迫切需要替代抗菌策略。抗菌肽(AMPs)可能是当前抗生素的有前途的替代品,或可作为佐剂增强抗生素效力。此外,使用可生物降解的脂质纳米颗粒可增强抗生素和抗菌肽的抗菌活性。在本研究中,研究了抗菌肽乳链菌肽Z和蜂毒肽与传统抗生素在金黄色葡萄球菌、表皮葡萄球菌和大肠杆菌上的相互作用。还评估了纳米结构脂质载体(NLCs)包封乳链菌肽Z的有效性。研究结果表明,乳链菌肽Z与多种传统抗生素表现出相加相互作用。新霉素-乳链菌肽Z组合观察到显著的协同作用。添加非抗生素佐剂乙二胺四乙酸(EDTA)显著提高了游离乳链菌肽Z对大肠杆菌的抗菌活性。含乳链菌肽Z的NLCs在生理pH值下对革兰氏阳性菌有效,在EDTA存在下有效性增加。结果表明,乳链菌肽Z作为抗菌化疗佐剂可能具有优势,同时有助于对抗抗生素耐药性。NLCs有潜力增强乳链菌肽Z对与皮肤感染相关的革兰氏阳性菌的抗菌活性。

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