Gene Expression Profiling of Pseudomonas aeruginosa Upon Exposure to Colistin and Tobramycin

Anastasia Cianciulli Sesso; Branislav Lilić; Fabian Amman; Michael T. Wolfinger; Elisabeth Sonnleitner; Udo Bläsi

doi:10.3389/fmicb.2021.626715

Title

Gene Expression Profiling of Pseudomonas aeruginosa Upon Exposure to Colistin and Tobramycin

Author

Anastasia Cianciulli Sesso

Department of Microbiology, Immunobiology and Genetics (until 2023-12-31), Centre for Molecular Biology (until 2023-12-31), University of Vienna

Branislav Lilić

Department of Microbiology, Immunobiology and Genetics (until 2023-12-31), Centre for Molecular Biology (until 2023-12-31), University of Vienna

Fabian Amman

Department of Theoretical Chemistry, Faculty of Chemistry, University of Vienna

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Abstract

Pseudomonas aeruginosa (Pae) is notorious for its high-level resistance toward clinically used antibiotics. In fact, Pae has rendered most antimicrobials ineffective, leaving polymyxins and aminoglycosides as last resort antibiotics. Although several resistance mechanisms of Pae are known toward these drugs, a profounder knowledge of hitherto unidentified factors and pathways appears crucial to develop novel strategies to increase their efficacy. Here, we have performed for the first time transcriptome analyses and ribosome profiling in parallel with strain PA14 grown in synthetic cystic fibrosis medium upon exposure to polymyxin E (colistin) and tobramycin. This approach did not only confirm known mechanisms involved in colistin and tobramycin susceptibility but revealed also as yet unknown functions/pathways. Colistin treatment resulted primarily in an anti-oxidative stress response and in the de-regulation of the MexT and AlgU regulons, whereas exposure to tobramycin led predominantly to a rewiring of the expression of multiple amino acid catabolic genes, lower tricarboxylic acid (TCA) cycle genes, type II and VI secretion system genes and genes involved in bacterial motility and attachment, which could potentially lead to a decrease in drug uptake. Moreover, we report that the adverse effects of tobramycin on translation are countered with enhanced expression of genes involved in stalled ribosome rescue, tRNA methylation and type II toxin-antitoxin (TA) systems.

Keywords

Pseudomonas aeruginosacolistintobramycinRNA-Seqribosome profilingRibo-seq

Object type

journal article

Language

English [eng]

Persistent identifier

phaidra.univie.ac.at/o:1621417

DOI

10.3389/fmicb.2021.626715

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