Challenges in using transcriptome data to study the c-di-GMP signaling network in Pseudomonas aeruginosa clinical isolates

Author:

Gür Melisa1ORCID,Erdmann Jelena1ORCID,Will Anke1ORCID,Liang Ziwei2ORCID,Andersen Jens Bo2ORCID,Tolker-Nielsen Tim2ORCID,Häussler Susanne134ORCID

Affiliation:

1. Institute for Molecular Bacteriology, TWINCORE, Centre for Experimental and Clinical Infection Research , Feodor-Lynen-Strasse 7, 30265 Hannover , Germany

2. Costerton Biofilm Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen , Blegdamsvej 3B 24.1, 2100 Copenhagen , Denmark

3. Department of Molecular Bacteriology, Helmholtz Centre for Infection Research , Inhoffenstrasse 7, 38124 Braunschweig , Germany

4. Department of Clinical Microbiology, Copenhagen University Hospital – Rigshospitalet , Ole Maaloes Vej 26, 2100 Copenhagen , Denmark

Abstract

Abstract In the Pseudomonas aeruginosa type strain PA14, 40 genes are known to encode for diguanylate cyclases (DGCs) and/or phosphodiesterases (PDEs), which modulate the intracellular pool of the nucleotide second messenger c-di-GMP. While in general, high levels of c-di-GMP drive the switch from highly motile phenotypes towards a sessile lifestyle, the different c-di-GMP modulating enzymes are responsible for smaller and in parts nonoverlapping phenotypes. In this study, we sought to utilize previously recorded P. aeruginosa gene expression datasets on 414 clinical isolates to uncover transcriptional changes as a result of a high expression of genes encoding DGCs. This approach might provide a unique opportunity to bypass the problem that for many c-di-GMP modulating enzymes it is not known under which conditions their expression is activated. However, while we demonstrate that the selection of subgroups of clinical isolates with high versus low expression of sigma factor encoding genes served the identification of their downstream regulons, we were unable to confirm the predicted DGC regulons, because the high c-di-GMP associated phenotypes were rapidly lost in the clinical isolates,. Further studies are needed to determine the specific mechanisms underlying the loss of cyclase activity upon prolonged cultivation of clinical P. aeruginosa isolates.

Funder

Deutsche Forschungsgemeinschaft

European Union

Novo Nordisk Foundation

Cystic Fibrosis Trust

Publisher

Oxford University Press (OUP)

Subject

General Earth and Planetary Sciences,General Engineering,General Environmental Science

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