摘要

通过抗性基因的突变或水平转移可以获得抗生素抗性，并且通常获得的机制导致表型抗性的可预测的增加。然而，最近的发现表明环境和/或遗传背景可以修饰特定抗性基因/突变的表型表达。这些发现的一个重要含义是给定的基因型并不总是导致预期的表型。这种基因型和表型的分离对临床细菌学和我们预测来自遗传学和DNA序列的抗性表型的能力具有重要影响。一个相关的问题涉及目前体外鉴定的基因/突变可以完全解释体内抗性表型，或者是否存在显着额外量的目前未知的突变/基因（遗传“暗物质”），其可能有助于临床分离株的耐药性。最后，一个非常重要的问题是我们是否能/如何确定有助于成功构建病原体的遗传特征，并预测为什么一些抗性克隆非常成功并在全球传播？在这篇综述中，我们描述了影响抗生素抗性基因/突变的表型表达的不同环境和遗传因素，以及如何了解这些信息以理解为什么特定的抗性克隆遍布全球以及我们可以使用DNA序列预测进化成功的程度。

Antibiotic resistance can be acquired by mutation or horizontal transfer of a resistance gene, and generally an acquired mechanism results in a predictable increase in phenotypic resistance. However, recent findings suggest that the environment and/or the genetic context can modify the phenotypic expression of specific resistance genes/mutations. An important implication from these findings is that a given genotype does not always result in the expected phenotype. This dissociation of genotype and phenotype has important consequences for clinical bacteriology and for our ability to predict resistance phenotypes from genetics and DNA sequences. A related problem concerns the degree to which the genes/mutations currently identified in vitro can fully explain the in vivo resistance phenotype, or whether there is a significant additional amount of presently unknown mutations/genes (genetic ‘dark matter’) that could contribute to resistance in clinical isolates. Finally, a very important question is whether/how we can identify the genetic features that contribute to making a successful pathogen, and predict why some resistant clones are very successful and spread globally? In this review, we describe different environmental and genetic factors that influence phenotypic expression of antibiotic resistance genes/mutations and how this information is needed to understand why particular resistant clones spread worldwide and to what extent we can use DNA sequences to predict evolutionary success.

https://academic.oup.com/femsre/article/41/3/374/3063351