Predicting drug resistance evolution: insights from antimicrobial peptides and antibiotics
Predicting drug resistance evolution: insights from antimicrobial peptides and antibiotics
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DOI：
10.1098/rspb.2017.2687
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发表时间：
2018-03-14
影响因子：
4.7
通讯作者：
Rolff, Jens
中科院分区：
文献类型：
--
作者：
Yu, Guozhi;Baeder, Desiree Y.;Rolff, Jens
抗生素耐药性是最紧迫的公共卫生问题之一。多细胞生物体的抗菌肽（AMP）被认为是解决这一问题的一部分，而由细菌产生的AMP（如粘菌素）是最后的药物。重要的是，AMP在药效学特征方面不同于许多抗生素。在这里，我们在一个理论框架内实现这些差异，以预测对AMP的耐药性的演变，并将其与抗生素耐药性进行比较。我们对耐药性演变的分析发现，药效学差异全部联合收割机组合产生对AMP的耐药性演变的概率低得多。这一发现可以推广到所有药效学与AMP相似的药物。药效学概念是医学微生物学的大多数从业者所熟悉的，并且可以容易地获得任何药物或药物组合的数据。因此，我们的理论和概念框架是广泛适用的，如果在抗生素管理计划或新药候选人的合理选择中实施，可以帮助避免耐药性演变。
Antibiotic resistance constitutes one of the most pressing public health concerns. Antimicrobial peptides (AMPs) of multicellular organisms are considered part of a solution to this problem, and AMPs produced by bacteria such as colistin are last-resort drugs. Importantly, AMPs differ from many antibiotics in their pharmacodynamic characteristics. Here we implement these differences within a theoretical framework to predict the evolution of resistance against AMPs and compare it to antibiotic resistance. Our analysis of resistance evolution finds that pharmacodynamic differences all combine to produce a much lower probability that resistance will evolve against AMPs. The finding can be generalized to all drugs with pharmacodynamics similar to AMPs. Pharmacodynamic concepts are familiar to most practitioners of medical microbiology, and data can be easily obtained for any drug or drug combination. Our theoretical and conceptual framework is, therefore, widely applicable and can help avoid resistance evolution if implemented in antibiotic stewardship schemes or the rational choice of new drug candidates.