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Allelic polymorphism shapes community function in evolving Pseudomonas aeruginosa populations

Abstract

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.

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Fig. 1: The evolutionary trajectory of P. aeruginosa during biofilm growth in SCFM.
Fig. 2: Allele frequency of SNPs changes over the course of selection.
Fig. 3: Phenotypes of evolved populations of PAO1.
Fig. 4: Loss of protease activity and a decrease in QS signal production in evolved populations can be explained by an accumulation of lasR SNPs.
Fig. 5: Increased resistance to ceftazidime and piperacillin/tazobactam in evolved populations is correlated with lasR SNP frequency.

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Acknowledgements

For funding, we thank the Human Frontier Science Program (RGY0081/2012) and Georgia Institute of Technology, The Cystic Fibrosis Foundation (DIGGLE18I0) to SPD, Cystic Fibrosis Foundation for a Fellowship to SA (AZIMI18F0), and CF@latna for a Fellowship to SA (3206AXB). We also thank The National Heart Lung Blood Institute (R56HL142857) and The Simons Foundation (396001) to SPB. We acknowledge Jacob Thomas for help with lasR complementation and Freya Harrison and James Gurney for helpful comments on the work. We also thank three anonymous referees for their helpful suggestions for improving this paper.

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Azimi, S., Roberts, A.E.L., Peng, S. et al. Allelic polymorphism shapes community function in evolving Pseudomonas aeruginosa populations. ISME J 14, 1929–1942 (2020). https://doi.org/10.1038/s41396-020-0652-0

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