Data from: Genotype-by-environment interactions due to antibiotic resistance and adaptation in Escherichia coli

Mutations that are beneficial in one environment can have different fitness effects in other environments. In the context of antibiotic resistance, the resulting genotype-by-environment interactions potentially make selection on resistance unpredictable in heterogeneous environments. Furthermore, resistant bacteria frequently fix additional mutations during evolution in the absence of antibiotics. How do these two types of mutations interact to determine the bacterial phenotype across different environments? To address this, I used Escherichia coli as a model system, measuring the effects of nine different rifampicin-resistance mutations on bacterial growth in 31 antibiotic-free environments. I did this both before and after approximately 200 generations of experimental evolution in antibiotic-free conditions (LB medium), and did the same for the antibiotic-sensitive wild type after adaptation to the same environment. Results: (1) bacteria with and without costly resistance mutations adapted to experimental conditions and reached similar levels of competitive fitness; (2) rifampicin-resistance mutations and adaptation to LB both indirectly altered growth in other environments; (3) resistant-evolved genotypes were more phenotypically different from the ancestor and from each other than resistant-non-evolved and sensitive-evolved genotypes. This suggests genotype-by-environment interactions generated by antibiotic resistance mutations, observed previously in short-term experiments, are more pronounced after adaptation to other types of environmental variation, making it difficult to predict long-term selection on resistance mutations from fitness effects in a single environment.

在某一环境中具有有益效应的突变，在其他环境中可能表现出迥异的适合度效应。在抗生素耐药性的研究背景下，由此产生的基因型-环境互作（genotype-by-environment interaction）可能使得异质环境中针对耐药性的选择难以预测。此外，耐药细菌在无抗生素的环境中演化时，往往会固定额外的突变。这两类突变如何共同作用，决定细菌在不同环境中的表型？

为解答这一问题，本研究以大肠杆菌（Escherichia coli）为模式系统，测定了9种不同利福平耐药性突变对细菌在31种无抗生素环境中生长的影响。我们在无抗生素条件（LB培养基）中开展约200代实验演化前后均进行了上述测定，并在抗生素敏感型野生菌株适应相同环境后，对其开展了相同的测定。

研究结果如下：
(1) 携带适合度成本耐药突变与未携带耐药突变的细菌均能适应实验条件，并达到相近的竞争适合度水平；
(2) 利福平耐药性突变与LB培养基适应过程均会间接改变细菌在其他环境中的生长表现；
(3) 经实验演化的耐药基因型，相较于未演化的耐药基因型与经演化的敏感基因型，与祖先菌株的表型差异更大，且彼此间的表型差异也更为显著。

上述结果表明，此前在短期实验中已观测到的、由抗生素耐药性突变引发的基因型-环境互作，在适应其他类型的环境变异后会更为显著，这意味着仅通过单一环境中的适合度效应，难以预测耐药性突变所受到的长期选择压力。