The α‐hydroxyketone LAI‐1 regulates motility, Lqs‐dependent phosphorylation signalling and gene expression of <i>Legionella pneumophila</i>

Schell, Ursula; Simon, Sylvia; Sahr, Tobias; Hager, Dominik; Albers, M.; Kessler, Aline; Fahrnbauer, Felix; Trauner, Dirk; Hedberg, Christian; Buchrieser, Carmen; Hilbi, Hubert

doi:10.1111/mmi.13265

Cited by 43 publications

(61 citation statements)

References 58 publications

(122 reference statements)

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“…pneumophila produces a quorum sensing autoinducer molecule, 3-hydroxypentadecane-4-one (LAI-1), that is synthesized by LqsA and sensed by the two sensor kinases LqsS and LqsT, which subsequently phosphorylate the response regulator LqsR [20, 41, 42]. Expression of LqsR was shown to be dependent on RpoS and LetA [22].…”

Section: Resultsmentioning

confidence: 99%

The Legionella pneumophila genome evolved to accommodate multiple regulatory mechanisms controlled by the CsrA-system

et al. 2017

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The carbon storage regulator protein CsrA regulates cellular processes post-transcriptionally by binding to target-RNAs altering translation efficiency and/or their stability. Here we identified and analyzed the direct targets of CsrA in the human pathogen Legionella pneumophila. Genome wide transcriptome, proteome and RNA co-immunoprecipitation followed by deep sequencing of a wild type and a csrA mutant strain identified 479 RNAs with potential CsrA interaction sites located in the untranslated and/or coding regions of mRNAs or of known non-coding sRNAs. Further analyses revealed that CsrA exhibits a dual regulatory role in virulence as it affects the expression of the regulators FleQ, LqsR, LetE and RpoS but it also directly regulates the timely expression of over 40 Dot/Icm substrates. CsrA controls its own expression and the stringent response through a regulatory feedback loop as evidenced by its binding to RelA-mRNA and links it to quorum sensing and motility. CsrA is a central player in the carbon, amino acid, fatty acid metabolism and energy transfer and directly affects the biosynthesis of cofactors, vitamins and secondary metabolites. We describe the first L. pneumophila riboswitch, a thiamine pyrophosphate riboswitch whose regulatory impact is fine-tuned by CsrA, and identified a unique regulatory mode of CsrA, the active stabilization of RNA anti-terminator conformations inside a coding sequence preventing Rho-dependent termination of the gap operon through transcriptional polarity effects. This allows L. pneumophila to regulate the pentose phosphate pathway and the glycolysis combined or individually although they share genes in a single operon. Thus the L. pneumophila genome has evolved to acclimate at least five different modes of regulation by CsrA giving it a truly unique position in its life cycle.

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Section: Resultsmentioning

confidence: 99%

The Legionella pneumophila genome evolved to accommodate multiple regulatory mechanisms controlled by the CsrA-system

et al. 2017

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“…LAI-1 promotes pathogen-host cell interactions, the production of virulence factors and controls the change of the L. pneumophila life cycle from the replicative to the transmissive growth phase. Interestingly, LAI-1 is directly involved in inter-kingdom signaling, as a lack of LAI-1 modulates migration of eukaryotic cells (Spirig et al, 2008; Tiaden et al, 2010; Simon et al, 2015; Schell et al, 2016). Moreover, V. harveyi uses amongst others (Z)-3-aminoundec-2-en-4-one as CAI-1 molecule to regulate luminescence, for example (Henke and Bassler, 2004).…”

Section: Discussionmentioning

confidence: 99%

Molecular Keys to the Janthinobacterium and Duganella spp. Interaction with the Plant Pathogen Fusarium graminearum

et al. 2016

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Janthinobacterium and Duganella are well-known for their antifungal effects. Surprisingly, almost nothing is known on molecular aspects involved in the close bacterium-fungus interaction. To better understand this interaction, we established the genomes of 11 Janthinobacterium and Duganella isolates in combination with phylogenetic and functional analyses of all publicly available genomes. Thereby, we identified a core and pan genome of 1058 and 23,628 genes. All strains encoded secondary metabolite gene clusters and chitinases, both possibly involved in fungal growth suppression. All but one strain carried a single gene cluster involved in the biosynthesis of alpha-hydroxyketone-like autoinducer molecules, designated JAI-1. Genome-wide RNA-seq studies employing the background of two isolates and the corresponding JAI-1 deficient strains identified a set of 45 QS-regulated genes in both isolates. Most regulated genes are characterized by a conserved sequence motif within the promoter region. Among the most strongly regulated genes were secondary metabolite and type VI secretion system gene clusters. Most intriguing, co-incubation studies of J. sp. HH102 or its corresponding JAI-1 synthase deletion mutant with the plant pathogen Fusarium graminearum provided first evidence of a QS-dependent interaction with this pathogen.

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“…The Lqs system is not conserved among Legionella species, but α-hydroxyketone-mediated signalling and cell-cell communication is widely distributed among environmental bacteria (Tiaden et al, 2010a). In addition to the growth phase switch of L. pneumophila, the Lqs system and LAI-1 regulate pathogen-host cell interactions (Personnic et al, 2018), bacterial as well as host cell motility (Simon et al, 2015;Schell et al, 2016), natural competence for DNA uptake (Kessler et al, 2013), filament formation and expression of a canonical chromosomal 'fitness island' (Tiaden et al, 2010b). The fitness island comprises about 125 genes (lpg0973-1096) and is arranged in two regions separated by lvrB1-lvrA1 (lpg1004-1005).…”

Section: Introductionmentioning

confidence: 99%

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

Hochstrasser

Kessler

Sahr

et al. 2019

Environmental Microbiology

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Summary 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.

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The α‐hydroxyketone LAI‐1 regulates motility, Lqs‐dependent phosphorylation signalling and gene expression of Legionella pneumophila

Cited by 43 publications

References 58 publications

The Legionella pneumophila genome evolved to accommodate multiple regulatory mechanisms controlled by the CsrA-system

The Legionella pneumophila genome evolved to accommodate multiple regulatory mechanisms controlled by the CsrA-system

Molecular Keys to the Janthinobacterium and Duganella spp. Interaction with the Plant Pathogen Fusarium graminearum

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

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