Pseudomonas aeruginosa biofilm formation on endotracheal tubes requires multiple two-component systems

Badal, Divakar; Jayarani, Abhijith Vimal; Kollaran, Mohammed Ameen; Kumar, Aloke; Singh, Varsha

doi:10.1099/jmm.0.001199

Cited by 25 publications

(27 citation statements)

References 109 publications

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“…Similar to other prokaryotic TFs, both activating or repressing phenotypes could be observed upon manipulating TF binding in P. aeruginosa (73,(84)(85)(86)(87)(88)(89)(90)(91). However, we observed that most mutant strains did not show an overt biofilm-associated phenotype, even those of some previously known positive TFs such as RsaL (92), CprR (46), AlgB (76,93), CdpR (75), BqsR (Synonym: CarR) (71, 72) and PA3782 (63).…”

Section: Pa0225 Is a Novel Regulator Of Biofilm Productionmentioning

confidence: 56%

An atlas of the binding specificities of transcription factors in Pseudomonas aeruginosa directs prediction of novel regulators in virulence

Wang

Sun

Fan

et al. 2021

eLife

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A high-throughput systematic evolution of ligands by exponential enrichment assay was applied to 371 putative TFs in P. aeruginosa, which resulted in the robust enrichment of 199 sequence motifs describing the binding specificities of 182 TFs. By scanning the genome, we predicted in total 33,709 significant interactions between TFs and their target loci, which were more than 11-fold enriched in the intergenic regions but depleted in the gene body regions. To further explore and delineate the physiological and pathogenic roles of TFs in P. aeruginosa, we constructed regulatory networks for nine major virulence-associated pathways, and found that 51 TFs were potentially significantly associated with these virulence pathways, 32 of which had not been characterized before, and some were even involved in multiple pathways. These results will significantly facilitate future studies on transcriptional regulation in P. aeruginosa and other relevant pathogens, and accelerate to discover effective treatment and prevention strategies for the associated infectious diseases.

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Section: Pa0225 Is a Novel Regulator Of Biofilm Productionmentioning

confidence: 56%

An atlas of the binding specificities of transcription factors in Pseudomonas aeruginosa directs prediction of novel regulators in virulence

Wang

Sun

Fan

et al. 2021

eLife

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“…production , and which will be discussed more below. The additional three evolved mutations in separate genes that have all been linked to Pseudomonas biofilm production previously: mutant D acquired a mutation in the sensor histidine kinase rcsC 55 , M acquired a mutation in the type III secretion system gene pscQ 56 , and V acquired a mutation in the two component response regulator PA14_52250 57,58 (Table 2). While these are not the only mutations that distinguish the morphotypes from one another, these are leading candidates that could produce their varied biofilm phenotypes.…”

Section: High Diversity Is a Byproduct Of Clonal Interferencementioning

confidence: 99%

“…D acquired a mutation in the sensor histidine kinase rcsC (Nicastro et al 2009), M acquired a mutation in the type III secretion system gene pscQ (Wagner et al 2003), and V acquired a mutation in the two component response regulator PA14_52250 (Francis et al 2017;Badal et al. 2020) ( Table 2.…”

Section: High Diversity Is a Byproduct Of Clonal Interferencementioning

confidence: 99%

Polygenic adaptation, clonal interference, and the evolution of mutators in experimentalPseudomonas aeruginosapopulations

Harris

Flynn

Cooper

2021

Preprint

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In bacterial populations, switches in lifestyle from motile, planktonic growth to surface-associated biofilm is associated with persistence both in the environment and infections. Studies have identified the first steps of adaptation to biofilm growth but have yet to replicate the extensive genetic diversity observed in chronic infections or in the natural environment. We conducted an evolution experiment with Pseudomonas aeruginosa PA14 in growth media that promotes biofilm formation for 90 days in either planktonic culture or in a biofilm bead model. Surprisingly, all populations evolved extensive genetic diversity with hundreds of mutations maintained at intermediate frequencies, while fixation events were rare. Instead of the expected few beneficial mutations rising in frequency through successive sweeps, we observe a remarkable 40 genes with parallel mutations spanning both environments and often on coexisting genotypes within a population. Additionally, the evolution of mutator genotypes (mutS or mutL mutator alleles) that rise to high frequencies in as little as 25 days contribute to the extensive genetic variation and strong clonal interference. Parallelism in several transporters (including pitA, pntB, nosD, and pchF) indicate probable adaptation to the arginine media that becomes highly alkaline during growth, whereas genes involved in signal transduction (including gacS, aer2, bdlA, and PA14_71750) reflect likely adaptations to biofilm-inducing conditions. This experiment shows how extensive genetic and phenotypic diversity can arise and persist in microbial populations despite strong selection that would normally purge diversity.

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“…TCSs are numerous in P. aeruginosa, about twice as abundant as in the model organism Escherichia coli, and those that have been studied were found to be pivotal for orchestrating important cellular processes such as antibiotic resistance or the socalled acute-to-chronic lifestyle switch (Valentini and Filloux, 2016). Recently, several attempts at the global characterization of TCSs relied on phenotypic characterization of loss-of-function mutants (Badal et al;Gellatly et al, 2018;Kollaran et al, 2019;Wang et al, 2021a). However, while bringing new information on selected phenotypes, this approach does not globally address direct RR-target regulatory interactions.…”

Section: Introductionmentioning

confidence: 99%

Determination of the Two-Component Systems regulatory network reveals core and accessory regulations across Pseudomonas aeruginosa lineages

Trouillon

Imbert

Villard

et al. 2021

Preprint

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Pseudomonas aeruginosa possesses one of the most complex bacterial regulatory networks, which largely contributes to its success as a human opportunistic pathogen. However, most of its transcription factors (TFs) are still uncharacterized and the potential intra-species variability in regulatory networks has been mostly ignored so far. Here, to provide a first global view of the two-component systems (TCSs) regulatory network in P. aeruginosa, we produced and purified all DNA-binding TCS response regulators (RRs) and used DAP-seq to map the genome-wide binding sites of these 55 TFs across the three major P. aeruginosa lineages. The resulting networks encompass about 40% of all genes in each strain and contain numerous new important regulatory interactions across most major physiological processes, including virulence and antibiotic resistance. Strikingly, the comparison between the three representative strains shows that about half of the detected targets are specific to only one or two of the tested strains, revealing a previously unknown large functional diversity of TFs within a single species. Three main mechanisms were found to drive this diversity, including differences in accessory genome content, as exemplified by the strain-specific plasmid in the IHMA87 outlier strain which harbors numerous binding sites of chromosomally-encoded RRs. Additionally, most RRs display potential auto-regulation or RR-RR cross-regulation, bringing to light the vast complexity of this network. Overall, we provide the first complete delineation of the TCS regulatory network in P. aeruginosa that will represent an important resource for future studies on this pathogen.

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Pseudomonas aeruginosa biofilm formation on endotracheal tubes requires multiple two-component systems

Cited by 25 publications

References 109 publications

An atlas of the binding specificities of transcription factors in Pseudomonas aeruginosa directs prediction of novel regulators in virulence

An atlas of the binding specificities of transcription factors in Pseudomonas aeruginosa directs prediction of novel regulators in virulence

Polygenic adaptation, clonal interference, and the evolution of mutators in experimentalPseudomonas aeruginosapopulations

Determination of the Two-Component Systems regulatory network reveals core and accessory regulations across Pseudomonas aeruginosa lineages

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