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Evolution of biofilm-adapted gene expression profiles in lasR-deficient clinical Pseudomonas aeruginosa isolates

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The overall success of a pathogenic microbe depends on its ability to efficiently adapt to challenging conditions in the human host. Long-term evolution experiments track and predict adaptive trajectories and have contributed significantly to our understanding of the driving forces of bacterial adaptation. In this study, we conducted a cross-sectional study instead of long-term longitudinal evolution experiments. We analyzed the transcriptional profiles as well as genomic sequence variations of a large number of clinical Pseudomonas aeruginosa isolates that have been recovered from different infected human sites. Convergent changes in gene expression patterns were found in different groups of clinical isolates. The majority of repeatedly observed expression patterns could be attributed to a defective lasR gene, which encodes the major quorum-sensing regulator LasR. Strikingly, the gene expression pattern of the lasR-defective strains appeared to reflect a transcriptional response that evolves in a direction consistent with growth within a biofilm. In a process of genetic assimilation, lasR-deficient P. aeruginosa isolates appear to constitutively express a biofilm-adapted transcriptional profile and no longer require a respective environmental trigger. Our results demonstrate that profiling the functional consequences of pathoadaptive mutations in clinical isolates reveals long-term evolutionary pathways and may explain the success of lasR mutants in the opportunistic pathogen P. aeruginosa in a clinical context.

TidsskriftNPJ biofilms and microbiomes
Udgave nummer1
StatusUdgivet - dec. 2022

Bibliografisk note

Funding Information:
We are indebted to Prof. Victor de Lorenzo and Dr. Pablo I. Nikel for sharing their plasmids and suggestions, and to Dr. Stephan Brouwer for generating the lasR deletion mutant. We gratefully thank Agnes Nielsen, Astrid Dröge, and Anna-Lena Hagemann for support with RNA-seq sample preparation, and excellent technical assistance. S.H. was funded by the European Union (EU, ERC Consolidator Grant COMBAT 724290) and received funding as part of the excellence cluster RESIST (Resolving Infection Susceptibility; EXC 2155). Furthermore, S.H. received funding from the German Research Foundation (DFG SPP 1879) and the Novo Nordisk Foundation (NNF 18OC0033946).

Publisher Copyright:
© 2022, The Author(s).

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