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Environ Microbiol. 2019 Mar;21(3):1035-1053. doi: 10.1111/1462-2920.14523. Epub 2019 Feb 22.

The pleiotropic Legionella transcription factor LvbR links the Lqs and c-di-GMP regulatory networks to control biofilm architecture and virulence.

Author information

1
Institute of Medical Microbiology, Faculty of Medicine, University of Zürich, Gloriastrasse 30, 8006 Zürich, Switzerland.
2
Max von Pettenkofer Institute, Faculty of Medicine, Ludwig-Maximilians University, Pettenkoferstrasse 9a, 80336 Munich, Germany.
3
Institut Pasteur, Unité de Biologie des Bactéries Intracellulaires, 28 Rue du Dr Roux, 75724 Paris, France.
4
CNRS UMR 3525, 28 Rue du Dr Roux, 75724 Paris, France.

Abstract

The causative agent of Legionnaires' disease, Legionella pneumophila, colonizes amoebae and biofilms in the environment. The opportunistic pathogen employs the Lqs (Legionella quorum sensing) system and the signalling molecule LAI-1 (Legionella autoinducer-1) to regulate virulence, motility, natural competence and expression of a 133 kb genomic "fitness island", including a putative novel regulator. Here, we show that the regulator termed LvbR is an LqsS-regulated transcription factor that binds to the promoter of lpg1056/hnox1 (encoding an inhibitor of the diguanylate cyclase Lpg1057), and thus, regulates proteins involved in c-di-GMP metabolism. LvbR determines biofilm architecture, since L. pneumophila lacking lvbR accumulates less sessile biomass and forms homogeneous mat-like structures, while the parental strain develops more compact bacterial aggregates. Comparative transcriptomics of sessile and planktonic ΔlvbR or ΔlqsR mutant strains revealed concerted (virulence, fitness island, metabolism) and reciprocally (motility) regulated genes in biofilm and broth respectively. Moreover, ΔlvbR is hyper-competent for DNA uptake, defective for phagocyte infection, outcompeted by the parental strain in amoebae co-infections and impaired for cell migration inhibition. Taken together, our results indicate that L. pneumophila LvbR is a novel pleiotropic transcription factor, which links the Lqs and c-di-GMP regulatory networks to control biofilm architecture and pathogen-host cell interactions.

PMID:
30623561
DOI:
10.1111/1462-2920.14523

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