Basis for the Essentiality of H-NS Family Members in Pseudomonas aeruginosa

Castang, Sandra; Dove, Simon L.

doi:10.1128/jb.00932-12

Cited by 61 publications

(74 citation statements)

References 67 publications

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“…We also tried to construct an mvaT mvaU double mutant strain but were unable to after multiple attempts. This result agrees with previous reports, which established that the presence of either MvaT or MvaU is necessary for cell viability in order to silence the expression of prophage genes encoded in the P. aeruginosa genome (52,53). The phenotypes displayed by each mutant strain were similar to what has been described in previous studies (14,54,55).…”

Section: Resultssupporting

confidence: 82%

CysB Negatively Affects the Transcription of pqsR and Pseudomonas Quinolone Signal Production in Pseudomonas aeruginosa

et al. 2015

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Pseudomonas aeruginosa is a Gram-negative bacterium that is ubiquitous in the environment, and it is an opportunistic pathogen that can infect a variety of hosts, including humans. During the process of infection, P. aeruginosa coordinates the expression of numerous virulence factors through the production of multiple cell-to-cell signaling molecules. The production of these signaling molecules is linked through a regulatory network, with the signal N-(3-oxododecanoyl) homoserine lactone and its receptor LasR controlling the induction of a second acyl-homoserine lactone signal and the Pseudomonas quinolone signal (PQS). LasR-mediated control of PQS occurs partly by activating the transcription of pqsR, a gene that encodes the PQS receptor and is necessary for PQS production. We show that LasR interacts with a single binding site in the pqsR promoter region and that it does not influence the transcription of the divergently transcribed gene, nadA. Using DNA affinity chromatography, we identified additional proteins that interact with the pqsR-nadA intergenic region. These include the H-NS family members MvaT and MvaU, and CysB, a transcriptional regulator that controls sulfur uptake and cysteine biosynthesis. We show that CysB interacts with the pqsR promoter and that CysB represses pqsR transcription and PQS production. Additionally, we provide evidence that CysB can interfere with the activation of pqsR transcription by LasR. However, as seen with other CysB-regulated genes, pqsR expression was not differentially regulated in response to cysteine levels. These findings demonstrate a novel role for CysB in influencing cell-to-cell signal production by P. aeruginosa. IMPORTANCEThe production of PQS and other 4-hydroxy-2-alkylquinolone (HAQs) compounds is a key component of the P. aeruginosa cellto-cell signaling network, impacts multiple physiological functions, and is required for virulence. PqsR directly regulates the genes necessary for HAQ production, but little is known about the regulation of pqsR. We identified CysB as a novel regulator of pqsR and PQS production, but, unlike other CysB-controlled genes, it does not appear to regulate pqsR in response to cysteine. This implies that CysB functions as both a cysteine-responsive and cysteine-unresponsive regulator in P. aeruginosa. Pseudomonas aeruginosa is a Gram-negative bacterium that is ubiquitous in the environment, due in part to its metabolic versatility that allows it to obtain the nutrients needed for growth from a wide variety of compounds (1). P. aeruginosa is also an opportunistic pathogen that can infect plants, nematodes, insects, and mammals (2-5). With regard to humans, it can cause a wide range of diseases and is a major cause of health care-associated illnesses and devastating chronic infections in cystic fibrosis patients (6, 7). In order to thrive under such a diverse range of conditions, P. aeruginosa utilizes complex regulatory networks to control gene expression. These networks include global regulatory systems that can direct l...

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Section: Resultssupporting

confidence: 82%

CysB Negatively Affects the Transcription of pqsR and Pseudomonas Quinolone Signal Production in Pseudomonas aeruginosa

et al. 2015

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“…4B). As type IV pili are the receptors that Pf4 utilizes to infect PAO1 (20), these findings are consistent with the loss or inactivation of type IV pili from Pf4-producing cells, which would impair the ability of PAO1ϩPf4 to disseminate (19).…”

Section: Resultssupporting

confidence: 72%

“…For example, the global transcriptional regulator MvaT represses Pf4 production in P. aeruginosa (20). Because MvaT also regulates several virulence genes (28), it is possible that the derepression of Pf4 is accompanied by altered expression of virulence genes, which may affect pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Filamentous Bacteriophage Produced by Pseudomonas aeruginosa Alters the Inflammatory Response and Promotes Noninvasive InfectionIn Vivo

et al. 2017

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Pseudomonas aeruginosa is an important opportunistic human pathogen that lives in biofilm-like cell aggregates at sites of chronic infection, such as those that occur in the lungs of patients with cystic fibrosis and nonhealing ulcers. During growth in a biofilm, P. aeruginosa dramatically increases the production of filamentous Pf bacteriophage (Pf phage). Previous work indicated that when in vivo Pf phage production was inhibited, P. aeruginosa was less virulent. However, it is not clear how the production of abundant quantities of Pf phage similar to those produced by biofilms under in vitro conditions affects pathogenesis. Here, using a murine pneumonia model, we show that the production of biofilm-relevant amounts of Pf phage prevents the dissemination of P. aeruginosa from the lung. Furthermore, filamentous phage promoted bacterial adhesion to mucin and inhibited bacterial invasion of airway epithelial cultures, suggesting that Pf phage traps P. aeruginosa within the lung. The in vivo production of Pf phage was also associated with reduced lung injury, reduced neutrophil recruitment, and lower cytokine levels. Additionally, when producing Pf phage, P. aeruginosa was less prone to phagocytosis by macrophages than bacteria not producing Pf phage. Collectively, these data suggest that filamentous Pf phage alters the progression of the inflammatory response and promotes phenotypes typically associated with chronic infection.

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“…Notable exceptions include the ortholog of H-NS in Salmonella and the semiredundant pair of H-NS-like NAPs in Pseudomonas aeruginosa, MvaT/MvaU (32,47). In both of these cases, the essential role of these NAPs is to silence the expression of horizontally acquired genes that are toxic when constitutively expressed.…”

Section: Discussionmentioning

confidence: 99%

Cell cycle progression inCaulobacterrequires a nucleoid-associated protein with high AT sequence recognition

Ricci

Melfi

Lasker

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Faithful cell cycle progression in the dimorphic bacterium Caulobacter crescentus requires spatiotemporal regulation of gene expression and cell pole differentiation. We discovered an essential DNA-associated protein, GapR, that is required for Caulobacter growth and asymmetric division. GapR interacts with adenine and thymine (AT)-rich chromosomal loci, associates with the promoter regions of cell cycle-regulated genes, and shares hundreds of recognition sites in common with known master regulators of cell cycle-dependent gene expression. GapR target loci are especially enriched in binding sites for the transcription factors GcrA and CtrA and overlap with nearly all of the binding sites for MucR1, a regulator that controls the establishment of swarmer cell fate. Despite constitutive synthesis, GapR accumulates preferentially in the swarmer compartment of the predivisional cell. Homologs of GapR, which are ubiquitous among the α-proteobacteria and are encoded on multiple bacteriophage genomes, also accumulate in the predivisional cell swarmer compartment when expressed in Caulobacter. The Escherichia coli nucleoid-associated protein H-NS, like GapR, selectively associates with AT-rich DNA, yet it does not localize preferentially to the swarmer compartment when expressed exogenously in Caulobacter, suggesting that recognition of AT-rich DNA is not sufficient for the asymmetric accumulation of GapR. Further, GapR does not silence the expression of H-NS target genes when expressed in E. coli, suggesting that GapR and H-NS have distinct functions. We propose that Caulobacter has co-opted a nucleoid-associated protein with high AT recognition to serve as a mediator of cell cycle progression.

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Basis for the Essentiality of H-NS Family Members in Pseudomonas aeruginosa

Cited by 61 publications

References 67 publications

CysB Negatively Affects the Transcription of pqsR and Pseudomonas Quinolone Signal Production in Pseudomonas aeruginosa

CysB Negatively Affects the Transcription of pqsR and Pseudomonas Quinolone Signal Production in Pseudomonas aeruginosa

Filamentous Bacteriophage Produced by Pseudomonas aeruginosa Alters the Inflammatory Response and Promotes Noninvasive InfectionIn Vivo

Cell cycle progression inCaulobacterrequires a nucleoid-associated protein with high AT sequence recognition

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