Pervasive genotype-by-environment interactions shape the fitness effects of antibiotic resistance mutations.
Pervasive genotype-by-environment interactions shape the fitness effects of antibiotic resistance mutations.
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DOI：
10.1098/rspb.2023.1030
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发表时间：
2023-08-30
影响因子：
4.7
通讯作者：
Lagator, Mato
中科院分区：
文献类型：
--
作者：
Soley, Jake K.;Jago, Matthew;Walsh, Calum J.;Khomarbaghi, Zahra;Howden, Benjamin P.;Lagator, Mato
抗生素抗性突变的适应性效应是抗性进化的主要驱动力。虽然营养环境影响细菌的适应性，但抗性的实验研究通常仅在单一环境中测量突变体的适应性。我们探讨了营养环境如何影响健身效果的利福平耐药rpoB突变大肠杆菌在几个条件下的出现和传播的阻力的存在下，初级或二级抗生素，或没有任何抗生素。普遍的基因型环境（GXE）的相互作用确定健身在所有的实验条件下，与排名顺序的健身在抗生素的存在和不存在强烈依赖于营养环境。GxE相互作用也影响了次级抗生素的附带作用的大小和方向，在某些情况下，如此剧烈，以至于在一种营养环境中高度敏感的突变体对另一种营养环境中的相同抗生素表现出交叉耐药性。很可能rpoB突变对全局转录组的mu-特异性影响支持了观察到的GxE相互作用。普遍存在的，特定的GxE相互作用突出了在实验和临床工作中研究抗性的进化和传播时很少做的事情的重要性：评估在一系列相关环境中的耐药性突变体的适应性。
The fitness effects of antibiotic resistance mutations are a major driver of resistance evolution. While the nutrient environment affects bacterial fitness, experimental studies of resistance typically measure fitness of mutants in a single environment only. We explored how the nutrient environment affected the fitness effects of rifampicin-resistant rpoB mutations in Escherichia coli under several conditions critical for the emergence and spread of resistance—the presence of primary or secondary antibiotic, or the absence of any antibiotic. Pervasive genotype-by-environment (GxE) interactions determined fitness in all experimental conditions, with rank order of fitness in the presence and absence of antibiotics being strongly dependent on the nutrient environment. GxE interactions also affected the magnitude and direction of collateral effects of secondary antibiotics, in some cases so drastically that a mutant that was highly sensitive in one nutrient environment exhibited cross-resistance to the same antibiotic in another. It is likely that the mutant-specific impact of rpoB mutations on the global transcriptome underpins the observed GxE interactions. The pervasive, mutant-specific GxE interactions highlight the importance of doing what is rarely done when studying the evolution and spread of resistance in experimental and clinical work: assessing fitness of antibiotic-resistant mutants across a range of relevant environments.
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