Synergistic microbicidal effect of cationic antimicrobial peptides and teicoplanin against planktonic and biofilm-encased Staphylococcus aureus
Synergistic microbicidal effect of cationic antimicrobial peptides and teicoplanin against planktonic and biofilm-encased Staphylococcus aureus
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DOI：
10.1016/j.ijantimicag.2018.10.002
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发表时间：
2019-02-01
影响因子：
10.8
通讯作者：
Zaat, Sebastian A. J.
中科院分区：
文献类型：
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作者：
Koppen, Bruce C.;Mulder, Patrick P. G.;Zaat, Sebastian A. J.
抗生素耐药性和生物膜形成是细菌感染治疗失败的主要原因。本研究旨在确定传统抗生素与新型合成抗菌肽和抗生物膜肽 (SAAP) 的协同组合，其灵感来自天然人类阳离子肽 LL-37 和血栓素-1 (TC-1) 的结构。 LL-37 启发的先导肽 SAAP-148 与不同类别的抗生素联合对抗金黄色葡萄球菌，并与替考拉宁显示出协同作用。 LL-37、LL-37 启发的 SAAP-276 和 TC-1 启发的 TC84 也观察到与替考拉宁的协同作用。有趣的是，没有观察到针对表皮葡萄球菌的协同作用。此外，替考拉宁与 SAAP-148 或 SAAP-276 联合显示出针对金黄色葡萄球菌生物膜的强烈相互作用。金黄色葡萄球菌中的 dltABCD 操纵子和 mprF 基因赋予对 LL-37 的抗性，但 SAAP-148 被证明对野生型、Delta dltA 和 Delta mprF 金黄色葡萄球菌菌株具有无差异的效力。当单独使用时，需要相对高浓度的 LL-37 和替考拉宁（分别为 30-120 μM 和 4-32 mg/L）才能杀死金黄色葡萄球菌。通过联合使用替考拉宁和 LL-37，克服了金黄色葡萄球菌对 LL-37 的耐药性。因此，替考拉宁增强了肽 LL-37，增强了先天防御的功效，并且将新型肽与替考拉宁组合提供了增强金黄色葡萄球菌感染（包括生物膜）治疗功效的潜力。 (c) 2018 年 Elsevier B.V. 和国际化疗协会。版权所有。
Antibiotic resistance and biofilm formation are the main reasons for failure in treatment of bacterial infections. This study aimed to identify synergistic combinations of conventional antibiotics and novel synthetic antimicrobial and antibiofilm peptides (SAAPs) inspired by the structures of the natural human cationic peptides LL-37 and thrombocidin-1 (TC-1). The LL-37-inspired lead peptide SAAP-148 was combined with antibiotics of different classes against Staphylococcus aureus, and showed synergy with teicoplanin. Synergy with teicoplanin was also observed with LL-37, the LL-37-inspired SAAP-276 and the TC-1-inspired TC84. Interestingly, no synergy was observed against Staphylococcus epidermidis. Furthermore, teicoplanin combined with SAAP-148 or SAAP-276 showed strong interaction against S. aureus biofilms. The dltABCD operon and the mprF gene in S. aureus conferred resistance to LL-37, but SAAP-148 proved to be indifferently potent against wild-type, Delta dltA and Delta mprF S. aureus strains. When used alone, relatively high concentrations of both LL-37 and teicoplanin (30-120 mu M and 4-32 mg/L, respectively) were required to kill S. aureus. Resistance to LL-37 in S. aureus was overcome by combined use of teicoplanin and LL-37. Thus, teicoplanin potentiates peptide LL-37, enhancing the efficacy of the innate defence, and combining the novel peptides with teicoplanin offers potential for enhanced efficacy of treatment of S. aureus infections, including biofilms. (c) 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.