Different species exposed to a common stress may adapt by mutations in shared pathways or in unique systems, depending on how past environments have molded their genomes. Understanding how diverse bacterial pathogens evolve in response to an antimicrobial treatment is a pressing example of this problem, where discovery of molecular parallelism could lead to clinically useful predictions. Evolution experiments with pathogens in environments containing antibiotics, combined with periodic whole-population genome sequencing, can be used to identify many contending routes to antimicrobial resistance. We separately propagated two clinically relevant Gram-negative pathogens, Pseudomonas aeruginosa and Acinetobacter baumannii, in increasing concentrations of tobramycin in two different environments each: planktonic and biofilm. Independently of the pathogen, the populations adapted to tobramycin selection by parallel evolution of mutations in fusA1, encoding elongation factor G, and ptsP, encoding phosphoenolpyruvate phosphotransferase. As neither gene is a direct target of this aminoglycoside, mutations to either are unexpected and underreported causes of resistance. Additionally, both species acquired antibiotic resistance-associated mutations that were more prevalent in the biofilm lifestyle than in the planktonic lifestyle; these mutations were in electron transport chain components in A. baumannii and lipopolysaccharide biosynthesis enzymes in P. aeruginosa populations. Using existing databases, we discovered site-specific parallelism of fusA1 mutations that extends across bacterial phyla and clinical isolates. This study suggests that strong selective pressures, such as antibiotic treatment, may result in high levels of predictability in molecular targets of evolution, despite differences between organisms’ genetic backgrounds and environments.

中文翻译：

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跨物种和环境的妥布霉素抗性的并行发展。

暴露于共同压力下的不同物种可能会适应共享途径或独特系统中的突变，这取决于过去的环境如何塑造了他们的基因组。认识到多种细菌病原体如何响应抗菌药物的处理是这个问题的紧迫例子，在该问题中发现分子平行性可能导致临床上有用的预测。在含有抗生素的环境中对病原体进行进化实验，并与定期的全种群基因组测序相结合，可用于确定许多抗药性的竞争途径。我们分别繁殖了两种临床相关的革兰氏阴性病原体，铜绿假单胞菌和鲍曼不动杆菌在两种不同的环境中，托普霉素的浓度不断增加：浮游生物和生物膜。与病原体无关，种群通过编码fusA1（编码延伸因子G）和ptsP（编码磷酸烯醇丙酮酸磷酸转移酶）突变的平行进化而适应妥布霉素的选择。由于这两个基因都不是该氨基糖苷的直接靶标，因此任何一个的突变都是出乎意料的，并且未报告耐药性的原因。此外，两个物种都获得了与抗生素抗性相关的突变，这种突变在生物膜生活方式中比在浮游生活方式中更为普遍。这些突变是鲍曼不动杆菌的电子传输链成分和铜绿假单胞菌中的脂多糖生物合成酶。人口。使用现有的数据库，我们发现了fusA1突变的位点特异性并行性，其跨细菌菌群和临床分离株。这项研究表明，尽管生物体的遗传背景和环境之间存在差异，但是诸如抗生素治疗等强大的选择性压力可能会导致进化分子目标的高度可预测性。