Pseudomonas aeruginosa is an opportunistic pathogen that chronically infects the lungs of individuals with cystic fibrosis (CF) by forming antibiotic-resistant biofilms. Emergence of phenotypically diverse isolates within CF P. aeruginosa populations has previously been reported; however, the impact of heterogeneity on social behaviors and community function is poorly understood. Here we describe how this heterogeneity impacts on behavioral traits by evolving the strain PAO1 in biofilms grown in a synthetic sputum medium for 50 days. We measured social trait production and antibiotic tolerance, and used a metagenomic approach to analyze and assess genomic changes over the duration of the evolution experiment. We found that (i) evolutionary trajectories were reproducible in independently evolving populations; (ii) over 60% of genomic diversity occurred within the first 10 days of selection. We then focused on quorum sensing (QS), a well-studied P. aeruginosa trait that is commonly mutated in strains isolated from CF lungs. We found that at the population level, (i) evolution in sputum medium selected for decreased the production of QS and QS-dependent traits; (ii) there was a significant correlation between lasR mutant frequency, the loss of protease, and the 3O-C12-HSL signal, and an increase in resistance to clinically relevant β-lactam antibiotics, despite no previous antibiotic exposure. Overall, our findings provide insights into the effect of allelic polymorphism on community functions in diverse P. aeruginosa populations. Further, we demonstrate that P. aeruginosa population and evolutionary dynamics can impact on traits important for virulence and can lead to increased tolerance to β-lactam antibiotics.

中文翻译：

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等位基因多态性塑造了进化中的铜绿假单胞菌种群的群落功能。

铜绿假单胞菌是一种机会性病原体，通过形成耐抗生素的生物膜，慢性感染囊性纤维化 (CF) 患者的肺部。以前曾报道过在 CF P. aeruginosa 种群中出现表型多样的分离株。然而，人们对异质性对社会行为和社区功能的影响知之甚少。在这里，我们通过在合成痰培养基中生长 50 天的生物膜中进化菌株 PAO1 来描述这种异质性如何影响行为特征。我们测量了社会性状的产生和抗生素耐受性，并使用宏基因组方法来分析和评估进化实验期间的基因组变化。我们发现（i）进化轨迹在独立进化的种群中是可重现的；(ii) 超过 60% 的基因组多样性发生在选择的前 10 天内。然后，我们专注于群体感应 (QS)，这是一种经过充分研究的铜绿假单胞菌性状，通常在从 CF 肺分离的菌株中发生突变。我们发现在种群水平上，（i）选择用于减少 QS 和 QS 依赖性性状的产生的痰培养基的进化；(ii) 尽管以前没有接触过抗生素，但 lasR 突变频率、蛋白酶的丢失和 3O-C12-HSL 信号以及对临床相关 β-内酰胺抗生素的耐药性增加之间存在显着相关性。总体而言，我们的研究结果提供了对等位基因多态性对不同铜绿假单胞菌群落功能影响的见解。此外，我们证明了 P.