Advanced transcriptomic analysis reveals the role of efflux pumps and media composition in antibiotic responses of Pseudomonas aeruginosa

Akanksha Rajput, Hannah Tsunemoto, Anand V. Sastry, Richard Szubin, Kevin Rychel, Siddharth M. Chauhan, Joe Pogliano, Bernhard O. Palsson*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

112 Downloads (Pure)

Abstract

Pseudomonas aeruginosa is an opportunistic pathogen and major cause of hospital-acquired infections. The virulence of P. aeruginosa is largely determined by its transcriptional regulatory network (TRN). We used 411 transcription profiles of P. aeruginosa from diverse growth conditions to construct a quantitative TRN by identifying independently modulated sets of genes (called iModulons) and their condition-specific activity levels. The current study focused on the use of iModulons to analyze the biofilm production and antibiotic resistance of P. aeruginosa. Our analysis revealed: (i) 116 iModulons, 81 of which show strong association with known regulators; (ii) novel roles of regulators in modulating antibiotics efflux pumps; (iii) substrate-efflux pump associations; (iv) differential iModulon activity in response to beta-lactam antibiotics in bacteriological and physiological media; (v) differential activation of 'Cell Division' iModulon resulting from exposure to different beta-lactam antibiotics and (vi) a role of the PprB iModulon in the stress-induced transition from planktonic to biofilm lifestyle. In light of these results, the construction of an iModulon-based TRN provides a transcriptional regulatory basis for key aspects of P. aeruginosa infection, such as antibiotic stress responses and biofilm formation. Taken together, our results offer a novel mechanistic understanding of P. aeruginosa virulence.

Original languageEnglish
JournalNucleic Acids Research
Volume50
Issue number17
Pages (from-to)9675-9688
ISSN0305-1048
DOIs
Publication statusPublished - 2022

Fingerprint

Dive into the research topics of 'Advanced transcriptomic analysis reveals the role of efflux pumps and media composition in antibiotic responses of Pseudomonas aeruginosa'. Together they form a unique fingerprint.

Cite this