Nonclassical antagonism between human lysozyme and AMPs against Pseudomonas aeruginosa.
Nonclassical antagonism between human lysozyme and AMPs against Pseudomonas aeruginosa.
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DOI：
10.1002/2211-5463.13094
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发表时间：
2021-03
期刊：
影响因子：
2.6
通讯作者：
Griswold KE
中科院分区：
文献类型：
--
作者：
Blumenthal I;Davis LR;Berman CM;Griswold KE
已知人溶菌酶（hlyys）和抗菌肽（AMPs）的组合表现出相加性或协同性活性，因此，它们具有治疗持续性和抗生素耐药感染的潜力。我们检测了hlyys与六种不同的amp联合使用时对铜绿假单胞菌的活性。与先前的报道相反，我们发现一些治疗相关的amp在特定浓度范围内与hys表现出惊人的拮抗相互作用。我们进一步发现合成的AMP Tet009可以抑制hys介导的细菌裂解。据我们所知，这些结果代表了hlyys和AMP之间拮抗作用的首次观察，他们建议未来开发裂解酶和AMP联合疗法时考虑拮抗相互作用的潜力。人溶菌酶（hlyys）和抗菌肽（AMPs）的组合通常对细菌病原体表现出协同作用，因此，它们具有治疗持续性和抗生素耐药感染的潜力。在这里，我们首次证明了hys和一些合成的AMP的组合表现出非经典的拮抗活性，这表明在AMP药物开发过程中需要考虑有害的hys相互作用。
Combinations of human lysozyme (hLYS) and antimicrobial peptides (AMPs) are known to exhibit either additive or synergistic activity, and as a result, they have therapeutic potential for persistent and antibiotic‐resistant infections. We examined hLYS activity against Pseudomonas aeruginosa when combined with six different AMPs. In contrast to prior reports, we discovered that some therapeutically relevant AMPs manifest striking antagonistic interactions with hLYS across particular concentration ranges. We further found that the synthetic AMP Tet009 can inhibit hLYS‐mediated bacterial lysis. To the best of our knowledge, these results represent the first observations of antagonism between hLYS and AMPs, and they advise that future development of lytic enzyme and AMP combination therapies considers the potential for antagonistic interactions. Combinations of human lysozyme (hLYS) and antimicrobial peptides (AMPs) typically manifest synergistic activity against bacterial pathogens, and as a result, they have therapeutic potential for persistent and antibiotic‐resistant infections. Here, for the first time, we show that combinations of hLYS and some synthetic AMPs exhibit nonclassical antagonistic activity, suggesting the need to consider detrimental hLYS interactions during AMP drug development.
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