ABSTRACT

Introduction

Microorganisms of clinical importance frequently develop resistance to drug therapy, now a growing problem. The experience with Mycobacterium tuberculosis is a representative example of increasing multi-drug resistance. To avoid reaching a crisis in which patients could be left without adequate treatment, a new strategy is needed. Anti-microbial therapy has historically targeted the mechanisms rather than origin of drug resistance, thus allowing microorganisms to adapt and survive.

Areas covered

This contribution analyses the historical development (1943–2020) of the evolution of multi-drug resistance by M. tuberculosis strains in light of Darwin’s and Lamarck’s theories of evolution.

Expert opinion

Regarding the molecular origin of microbial drug resistance, genetic mutations and epigenetic modifications are known to participate. The analysis of the history of drug resistance by M. tuberculosis evidences a gradual development of resistance to some antibiotics, undoubtedly due to random mutations together with natural selection based on environmental pressures (e.g., antibiotics), representing Darwin’s idea. More rapid adaptation of M. tuberculosis to new antibiotic treatments has also occurred, probably because of heritable acquired characteristics, evidencing Lamarck’s proposal. Therefore, microbial infections should be treated with an antibiotic producing null or low mutagenic activity along with a resistance inhibitor, preferably in a single medication.

中文翻译：

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微生物耐药性增长的根源是什么？拉马克和达尔文都是对的

摘要

介绍

具有临床重要性的微生物经常对药物治疗产生耐药性，这是一个日益严重的问题。结核分枝杆菌的经验是增加多药耐药性的一个典型例子。为了避免出现患者得不到充分治疗的危机，需要一种新的策略。抗微生物治疗历来针对机制而不是耐药性的起源，从而使微生物能够适应和生存。

覆盖区域

本贡献根据达尔文和拉马克的进化理论分析了结核分枝杆菌菌株对多重耐药性进化的历史发展（1943-2020 年）。

专家意见

关于微生物耐药性的分子起源，已知基因突变和表观遗传修饰参与其中。对结核分枝杆菌耐药史的分析表明，对某些抗生素的耐药性逐渐发展，这无疑是由于随机突变以及基于环境压力（例如抗生素）的自然选择，代表了达尔文的想法。结核分枝杆菌对新抗生素治疗的更快速适应也发生了，可能是因为遗传的获得性特征，证明了拉马克的提议。因此，微生物感染应使用产生无效或低致突变活性的抗生素和抗性抑制剂一起治疗，最好是在单一药物中。