The MarR-Type Regulator PA3458 Is Involved in Osmoadaptation Control in Pseudomonas aeruginosa

Pseudomonas aeruginosa is a facultative human pathogen, causing acute and chronic infections that are especially dangerous for immunocompromised patients. The eradication of P. aeruginosa is difficult due to its intrinsic antibiotic resistance mechanisms, high adaptability, and genetic plasticity. The bacterium possesses multilevel regulatory systems engaging a huge repertoire of transcriptional regulators (TRs). Among these, the MarR family encompasses a number of proteins, mainly acting as repressors, which are involved in response to various environmental signals. In this work, we aimed to decipher the role of PA3458, a putative MarR-type TR from P. aeruginosa. Transcriptional profiling of P. aeruginosa PAO1161 overexpressing PA3458 showed changes in the mRNA level of 133 genes; among them, 100 were down-regulated, suggesting the repressor function of PA3458. Concomitantly, ChIP-seq analysis identified more than 300 PA3458 binding sites in P. aeruginosa. The PA3458 regulon encompasses genes involved in stress response, including the PA3459–PA3461 operon, which is divergent to PA3458. This operon encodes an asparagine synthase, a GNAT-family acetyltransferase, and a glutamyl aminopeptidase engaged in the production of N-acetylglutaminylglutamine amide (NAGGN), which is a potent bacterial osmoprotectant. We showed that PA3458-mediated control of PA3459–PA3461 expression is required for the adaptation of P. aeruginosa growth in high osmolarity. Overall, our data indicate that PA3458 plays a role in osmoadaptation control in P. aeruginosa.

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Increased ParB level affects expression of stress response, adaptation and virulence operons and potentiates repression of promoters adjacent to the high affinity binding sites parS3 and parS4 in Pseudomonas aeruginosa

10.1101/151340 ◽

2017 ◽

Author(s):

Adam Kawałek ◽

Krzysztof Głąbski ◽

Aneta Agnieszka Bartosik ◽

Anna Fogtman ◽

Grażyna Jagura-Burdzy

Keyword(s):

Growth Rate ◽

Pseudomonas Aeruginosa ◽

Chromosome Segregation ◽

Binding Sites ◽

Mrna Level ◽

Regulation Of Gene Expression ◽

High Affinity ◽

Bacteria Inactivation ◽

The Impact

AbstractSimilarly to its homologs in other bacteria, Pseudomonas aeruginosa partitioning protein ParB facilitates segregation of newly replicated chromosomes. Lack of ParB is not lethal but results in increased frequency of anucleate cells production, longer division time, cell elongation, altered colony morphology and defective swarming and swimming motility. Unlike in other bacteria, inactivation of parB leads to major changes of the transcriptome, suggesting that, directly or indirectly, ParB plays a role in regulation of gene expression in this organism.ParB overproduction affects growth rate, cell division and motility in a similar way as ParB deficiency. To identify primary ParB targets, here we analysed the impact of a slight increase in ParB level on P. aeruginosa transcriptome. ParB excess, which does not cause changes in growth rate and chromosome segregation, significantly alters the expression of 176 loci. Most notably, the mRNA level of genes adjacent to high affinity ParB binding sites parS1-4 close to oriC is reduced. Conversely, in cells lacking either parB or functional parS sequences the orfs adjacent to parS3 and parS4 are upregulated, indicating that direct ParB-parS3/parS4 interactions repress the transcription in this region. In addition, increased ParB level brings about repression or activation of numerous genes including several transcriptional regulators involved in SOS response, virulence and adaptation. Overall, our data support the role of partitioning protein ParB as a transcriptional regulator in Pseudomonas aeruginosa.

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PrtR Homeostasis Contributes to Pseudomonas aeruginosa Pathogenesis and Resistance against Ciprofloxacin

Infection and Immunity ◽

10.1128/iai.01388-13 ◽

2014 ◽

Vol 82 (4) ◽

pp. 1638-1647 ◽

Cited By ~ 28

Author(s):

Ziyu Sun ◽

Jing Shi ◽

Chang Liu ◽

Yongxin Jin ◽

Kewei Li ◽

...

Keyword(s):

Gene Expression ◽

Pseudomonas Aeruginosa ◽

Bacterial Colonization ◽

Mrna Level ◽

Sos Response ◽

Opportunistic Pathogen ◽

Host Cells ◽

Chronic Infections ◽

Mobility Shift ◽

Content Type

ABSTRACTPseudomonas aeruginosais an opportunistic pathogen that causes acute and chronic infections in humans. Pyocins are bacteriocins produced byP. aeruginosathat are usually released through lysis of the producer strains. Expression of pyocin genes is negatively regulated by PrtR, which gets cleaved under SOS response, leading to upregulation of pyocin synthetic genes. Previously, we demonstrated that PrtR is required for the expression of type III secretion system (T3SS), which is an important virulence component ofP. aeruginosa. In this study, we demonstrate that mutation inprtRresults in reduced bacterial colonization in a mouse acute pneumonia model. Examination of bacterial and host cells in the bronchoalveolar lavage fluids from infected mice revealed that expression of PrtR is induced by reactive oxygen species (ROS) released by neutrophils. We further demonstrate that treatment with hydrogen peroxide or ciprofloxacin, known to induce the SOS response and pyocin production, resulted in an elevated PrtR mRNA level. Overexpression of PrtR by atacpromoter repressed the endogenousprtRpromoter activity, and electrophoretic mobility shift assay revealed that PrtR binds to its own promoter, suggesting an autorepressive mechanism of regulation. A high level of PrtR expressed from a plasmid resulted in increased T3SS gene expression during infection and higher resistance against ciprofloxacin. Overall, our results suggest that the autorepression of PrtR contributes to the maintenance of a relatively stable level of PrtR, which is permissive to T3SS gene expression in the presence of ROS while increasing bacterial tolerance to stresses, such as ciprofloxacin, by limiting pyocin production.

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Epidemiology and carbapenem resistance mechanisms in Pseudomonas aeruginosa : Role of high-risk clones in multidrug resistance

Enfermedades infecciosas y microbiologia clinica (English ed ) ◽

10.1016/j.eimce.2017.02.006 ◽

2017 ◽

Vol 35 (3) ◽

pp. 137-138

Author(s):

Antonio Oliver

Keyword(s):

Pseudomonas Aeruginosa ◽

Multidrug Resistance ◽

High Risk ◽

Carbapenem Resistance ◽

Resistance Mechanisms

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Role of small RNA-based regulatory systems in cystic fibrosis airways infection by Pseudomonas aeruginosa: a new frontier in the identification of molecular targets for novel antibacterials

Postdoc Journal ◽

10.14304/ffc2016proceedings.10 ◽

2016 ◽

Author(s):

Ferrara S et al

Keyword(s):

Cystic Fibrosis ◽

Pseudomonas Aeruginosa ◽

Small Rna ◽

Molecular Targets ◽

Regulatory Systems ◽

New Frontier

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Recent advances in understanding Pseudomonas aeruginosa as a pathogen

F1000Research ◽

10.12688/f1000research.10506.1 ◽

2017 ◽

Vol 6 ◽

pp. 1261 ◽

Cited By ~ 63

Author(s):

Jens Klockgether ◽

Burkhard Tümmler

Keyword(s):

Pseudomonas Aeruginosa ◽

Population Biology ◽

Recent Progress ◽

Human Subjects ◽

Opportunistic Pathogen ◽

Mammalian Host ◽

Secretion Systems ◽

Chronic Infections ◽

Type Vi Secretion

The versatile and ubiquitousPseudomonas aeruginosais an opportunistic pathogen causing acute and chronic infections in predisposed human subjects. Here we review recent progress in understandingP. aeruginosapopulation biology and virulence, its cyclic di-GMP-mediated switches of lifestyle, and its interaction with the mammalian host as well as the role of the type III and type VI secretion systems inP. aeruginosainfection.

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PmrB Mutations Promote Polymyxin Resistance of Pseudomonas aeruginosa Isolated from Colistin-Treated Cystic Fibrosis Patients

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.05829-11 ◽

2011 ◽

Vol 56 (2) ◽

pp. 1019-1030 ◽

Cited By ~ 106

Author(s):

Samuel M. Moskowitz ◽

Mark K. Brannon ◽

Nandini Dasgupta ◽

Miyuki Pier ◽

Nicole Sgambati ◽

...

Keyword(s):

Cystic Fibrosis ◽

Pseudomonas Aeruginosa ◽

Lipid A ◽

Clinical Isolates ◽

Gain Of Function ◽

Content Type ◽

Regulatory Systems ◽

Repeated Passage ◽

High Level

ABSTRACTPseudomonas aeruginosacan develop resistance to polymyxin and other cationic antimicrobial peptides. Previous work has shown that mutations in the PmrAB and PhoPQ regulatory systems can confer low to moderate levels of colistin (polymyxin E) resistance in laboratory strains and clinical isolates of this organism (MICs of 8 to 64 mg/liter). To explore the role of PmrAB in high-level clinical polymyxin resistance,P. aeruginosaisolates from chronically colistin-treated cystic fibrosis patients, most with colistin MICs of >512 mg/liter, were analyzed. These cystic fibrosis isolates contained probable gain-of-functionpmrBalleles that conferred polymyxin resistance to strains with a wild-type orpmrABdeletion background. Double mutantpmrBalleles that contained mutations in both the periplasmic and dimerization-phosphotransferase domains markedly augmented polymyxin resistance. Expression of mutantpmrBalleles induced transcription from the promoter of thearnBoperon and stimulated addition of 4-amino-l-arabinose to lipid A, consistent with the known role of this lipid A modification in polymyxin resistance. For some highly polymyxin-resistant clinical isolates, repeated passage without antibiotic selection pressure resulted in loss of resistance, suggesting that secondary suppressors occur at a relatively high frequency and account for the instability of this phenotype. These results indicate thatpmrBgain-of-function mutations can contribute to high-level polymyxin resistance in clinical strains ofP. aeruginosa.

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ZINC-FINGER interactions mediate transcriptional regulation of hypocotyl growth in Arabidopsis

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1718099115 ◽

2018 ◽

Vol 115 (19) ◽

pp. E4503-E4511 ◽

Cited By ~ 5

Author(s):

Giorgio Perrella ◽

Mhairi L. H. Davidson ◽

Liz O’Donnell ◽

Ana-Marie Nastase ◽

Pawel Herzyk ◽

...

Keyword(s):

Transcription Factor ◽

Zinc Finger ◽

Transcriptional Regulators ◽

Hypocotyl Elongation ◽

Transcriptional Level ◽

Hypocotyl Growth ◽

Environmental Signals ◽

Genome Wide ◽

A Genome

Integration of environmental signals and interactions among photoreceptors and transcriptional regulators is key in shaping plant development. TANDEM ZINC-FINGER PLUS3 (TZP) is an integrator of light and photoperiodic signaling that promotes flowering in Arabidopsis thaliana. Here we elucidate the molecular role of TZP as a positive regulator of hypocotyl elongation. We identify an interacting partner for TZP, the transcription factor ZINC-FINGER HOMEODOMAIN 10 (ZFHD10), and characterize its function in coregulating the expression of blue-light–dependent transcriptional regulators and growth-promoting genes. By employing a genome-wide approach, we reveal that ZFHD10 and TZP coassociate with promoter targets enriched in light-regulated elements. Furthermore, using a targeted approach, we show that ZFHD10 recruits TZP to the promoters of key coregulated genes. Our findings not only unveil the mechanism of TZP action in promoting hypocotyl elongation at the transcriptional level but also assign a function to an uncharacterized member of the ZFHD transcription factor family in promoting plant growth.

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Review of Ceftazidime-Avibactam for the Treatment of Infections Caused by Pseudomonas aeruginosa

Antibiotics ◽

10.3390/antibiotics10091126 ◽

2021 ◽

Vol 10 (9) ◽

pp. 1126

Author(s):

George L. Daikos ◽

Clóvis Arns da da Cunha ◽

Gian Maria Rossolini ◽

Gregory G. Stone ◽

Nathalie Baillon-Plot ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Multidrug Resistant ◽

Resistance Mechanisms ◽

Real World Data ◽

Serious Infections ◽

Tract Infections ◽

Abdominal Infections ◽

Hospital Acquired

Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen that causes a range of serious infections that are often challenging to treat, as this pathogen can express multiple resistance mechanisms, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) phenotypes. Ceftazidime–avibactam is a combination antimicrobial agent comprising ceftazidime, a third-generation semisynthetic cephalosporin, and avibactam, a novel non-β-lactam β-lactamase inhibitor. This review explores the potential role of ceftazidime–avibactam for the treatment of P. aeruginosa infections. Ceftazidime–avibactam has good in vitro activity against P. aeruginosa relative to comparator β-lactam agents and fluoroquinolones, comparable to amikacin and ceftolozane–tazobactam. In Phase 3 clinical trials, ceftazidime–avibactam has generally demonstrated similar clinical and microbiological outcomes to comparators in patients with complicated intra-abdominal infections, complicated urinary tract infections or hospital-acquired/ventilator-associated pneumonia caused by P. aeruginosa. Although real-world data are limited, favourable outcomes with ceftazidime–avibactam treatment have been reported in some patients with MDR and XDR P. aeruginosa infections. Thus, ceftazidime–avibactam may have a potentially important role in the management of serious and complicated P. aeruginosa infections, including those caused by MDR and XDR strains.

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