Polymicrobial infections can select against Pseudomonas aeruginosa mutators because of quorum-sensing trade-offs

Adela M. Luján*, Steve Paterson, Elze Hesse, Lea M. Sommer, Rasmus L. Marvig, M. D. Sharma, Ellinor O. Alseth, Oana Ciofu, Andrea M. Smania, Søren Molin, Helle Krogh Johansen, Angus Buckling

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review


Bacteria with increased mutation rates (mutators) are common in chronic infections and are associated with poorer clinical outcomes, especially in the case of Pseudomonas aeruginosa infecting cystic fibrosis (CF) patients. There is, however, considerable between-patient variation in both P. aeruginosa mutator frequency and the composition of co-infecting pathogen communities. We investigated whether community context might affect selection of mutators. Using an in vitro CF model community, we show that P. aeruginosa mutators were favoured in the absence of other species but not in their presence. This was because there were trade-offs between adaptation to the biotic and abiotic environments (for example, loss of quorum sensing and associated toxin production was beneficial in the latter but not the former in our in vitro model community) limiting the evolvability advantage of an elevated mutation rate. Consistent with a role of co-infecting pathogens selecting against P. aeruginosa mutators in vivo, we show that the mutation frequency of P. aeruginosa population was negatively correlated with the frequency and diversity of co-infecting bacteria in CF infections. Our results suggest that co-infecting taxa can select against P. aeruginosa mutators, which may have potentially beneficial clinical consequences.

Original languageEnglish
JournalNature Ecology and Evolution
Issue number7
Pages (from-to)979-988
Number of pages10
Publication statusPublished - 2022

Bibliographical note

Funding Information:
We would like to thank J. P. Pirnay and D. de Vos for providing the bacterial community strains and A. Frias for generating the illustration shown in Extended Data Fig. 1. A.M.L. was supported by FP7 Marie Skłodowska-Curie International Incoming Fellowship (IIF) (no. 331163) and CONICET. E.H. was supported by KRI Future Leaders Fellowship (MR/V022482/1). A.M.S. was funded by ANPCyT (PICT-2016-1545 and PICT-2019-1590). S.M. was supported by Novo Nordisk Foundation Center for Biosustainability (CFB) (NNF10CC1016517). H.K.J. was supported by the Novo Nordisk Foundation as a clinical research stipend (NNF12OC1015920), by Rigshospitalets Rammebevilling 2015–17 (R88-A3537), by Lundbeckfonden (R167-2013-15229), by the Novo Nordisk Foundation (NNF15OC0017444), by RegionH Rammebevilling (R144-A5287) and by Independent Research Fund Denmark/Medical and Health Sciences (FTP-4183-00051). A.B. is supported by NERC (NE/S000771/1 and NE/V012347/1).

Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature Limited.


Dive into the research topics of 'Polymicrobial infections can select against Pseudomonas aeruginosa mutators because of quorum-sensing trade-offs'. Together they form a unique fingerprint.

Cite this