细菌附属敏感性:优化药物治疗的新思路

Bacterial Collateral Sensitivity:A New Perspective to Optimize Treatments

交叉耐药性(crossresistance)是指细菌耐药性进化过程中,对单一药物产生耐药性的同时,也会对结构或作用机理相似的药物产生耐药性的现象。附属敏感性(collateral sensitivity)则指细菌对某一药物敏感性下降时,反而对其他药物敏感性提高的现象。在抗菌药物的持续压力下,细菌会选择性地发生交叉耐药性或附属敏感性两种不同的进化路径。在后抗生素来临的时代背景下,科学家提出了一种新颖的治疗思路:借用细菌对药物的附属敏感性特征进行治疗方案的设计或优化。然而,细菌附属敏感性进化是极为复杂的过程,其发生概率不稳定且规律性不强。为更好地认知细菌附属敏感性的进化规律及应用前景,本文对影响细菌附属敏感性的关键因素及附属敏感性的产生规律进行综述,并以此提出目前研究的不足以及未来发展的可能方向。

“Cross resistance”(CR)is a phenomenon in which the bacteria have evolved to resist different types of antimicrobial molecules with similar structure or mechanisms of action,while“collateral sensitivity”(CS)can be defined as a situation where the bacteria have developed resistance to one antibiotic showed increased susceptibility to another antibiotic.The evolution of bacterial resistance is a complicated process that can either lead to cross resistance or collateral sensitivity under the selection pressure from antibiotics.Recently,CS has been proposed as a promising alternative approach to counteract the rising problem of antibiotic resistance.To better understand the mechanisms by which bacterial collateral sensitivity has been evolved and the application prospect of CS,in this review,we summarized our current knowledges on key factors influencing the bacterial collateral sensitivity and the regularities of CS.We also discuss directions and challenges for developing CS-informed treatment strategies.