scholarly journals Differential Role of Two-Component Regulatory Systems (<i>phoPQ</i> and <i>pmrAB</i>) in Polymyxin B Susceptibility of <i>Pseudomonas aeruginosa</i>

2012 ◽  
Vol 02 (01) ◽  
pp. 31-36 ◽  
Author(s):  
Daniel Owusu-Anim ◽  
Dong H. Kwon
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Polymyxin B ◽  
Regulatory Systems ◽  
Two Component

scholarly journals Contribution of the PhoP-PhoQ and PmrA-PmrB Two-Component Regulatory Systems to Mg2+-Induced Gene Regulation in Pseudomonas aeruginosa

2006 ◽  
Vol 188 (11) ◽  
pp. 3995-4006 ◽  
Author(s):  
Joseph B. McPhee ◽  
Manjeet Bains ◽  
Geoff Winsor ◽  
Shawn Lewenza ◽  
Agnieszka Kwasnicka ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Transcriptional Profiling ◽  
Polymyxin B ◽  
Dependent Manner ◽  
Binding Assays ◽  
Response Regulators ◽  
Binding Motifs ◽  
Regulatory Systems ◽  
Two Component ◽  
Genes Encoding

ABSTRACT When grown in divalent cation-limited medium, Pseudomonas aeruginosa becomes resistant to cationic antimicrobial peptides and polymyxin B. This resistance is regulated by the PhoP-PhoQ and PmrA-PmrB two-component regulatory systems. To further characterize Mg2+ regulation in P. aeruginosa, microarray transcriptional profiling was conducted to compare wild-type P. aeruginosa grown under Mg2+-limited and Mg2+-replete conditions to isogenic phoP and pmrA mutants grown under Mg2+-limited conditions. Under Mg2+-limited conditions (0.02 mM Mg2+), approximately 3% of the P. aeruginosa genes were differentially expressed compared to the expression in bacteria grown under Mg2+-replete conditions (2 mM Mg2+). Only a modest subset of the Mg2+-regulated genes were regulated through either PhoP or PmrA. To determine which genes were directly regulated, a bioinformatic search for conserved binding motifs was combined with confirmatory reverse transcriptase PCR and gel shift promoter binding assays, and the results indicated that very few genes were directly regulated by these response regulators. It was found that in addition to the previously known oprH-phoP-phoQ operon and the pmrHFIJKLM-ugd operon, the PA0921 and PA1343 genes, encoding small basic proteins, were regulated by Mg2+ in a PhoP-dependent manner. The number of known PmrA-regulated genes was expanded to include the PA1559-PA1560, PA4782-PA4781, and feoAB operons, in addition to the previously known PA4773-PA4775-pmrAB and pmrHFIJKLM-ugd operons.

scholarly journals Alterations in Two-Component Regulatory Systems of phoPQ and pmrAB Are Associated with Polymyxin B Resistance in Clinical Isolates of Pseudomonas aeruginosa

2009 ◽  
Vol 53 (12) ◽  
pp. 5150-5154 ◽  
Author(s):  
Kaddy Barrow ◽  
Dong H. Kwon
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Amino Acid ◽  
Polymyxin B ◽  
Clinical Isolates ◽  
Single Amino Acid ◽  
Amino Acid Substitutions ◽  
Strain Pao1 ◽  
Truncated Protein ◽  
Regulatory Systems ◽  
Two Component

ABSTRACT Polymyxins are often the only option to treat acquired multidrug-resistant Pseudomonas aeruginosa. Polymyxin susceptibility in P. aeruginosa PAO1 is associated with the lipopolysaccharide structure that is determined by arnBCADTEF and modulated by phoPQ and pmrAB. We examined five clonally unrelated clinical isolates of polymyxin B-resistant P. aeruginosa to investigate the molecular basis of polymyxin resistance. All isolates grew with 4 μg/ml polymyxin B (MIC, 8 μg/ml), whereas P. aeruginosa PAO1 grew with 0.25 μg/ml polymyxin B (MIC, 0.5 μg/ml). The resistant isolates were converted to susceptible ones (the MICs fell from 8 to 0.5 μg/ml) following the introduction of phoPQ (four isolates) and pmrAB (one isolate), which had been cloned from strain PAO1. DNA sequence analysis revealed that a single-nucleotide substitution in three isolates replaced a single amino acid of PhoQ, the deletion of 17 nucleotides in one isolate truncated the protein of PhoQ, and two nucleotide substitutions in one isolate replaced two amino acids of PmrB. The involvement of these amino acid substitutions or the truncated protein of PhoQ and PmrB in polymyxin B resistance was confirmed using strain PAO1 lacking phoPQ or pmrAB that was transformed by phoPQ or pmrAB containing the amino acid substitutions or the truncated protein. The resistant clinical isolates were sensitized by the inactivation of arnBCADTEF (the MICs fell from 8 to 0.5 μg/ml). These results suggest that polymyxin B resistance among clinical isolates of P. aeruginosa is associated with alterations in two-component regulatory systems of phoPQ or pmrAB.

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

2021 ◽  
Vol 22 (8) ◽  
pp. 3982
Author(s):  
Karolina Kotecka ◽  
Adam Kawalek ◽  
Kamil Kobylecki ◽  
Aneta Agnieszka Bartosik
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Binding Sites ◽  
Transcriptional Profiling ◽  
Mrna Level ◽  
Transcriptional Regulators ◽  
Resistance Mechanisms ◽  
Chronic Infections ◽  
Environmental Signals ◽  
Regulatory Systems

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.

The role of two-component regulatory systems in environmental sensing and virulence in Salmonella

2021 ◽  
pp. 1-38
Author(s):  
Lucindo Cardoso de Pina ◽  
Fernanda Stephens Hermes da Silva ◽  
Teca Calcagno Galvão ◽  
Heidi Pauer ◽  
Rosana Barreto Rocha Ferreira ◽  
...  
Keyword(s):  
Environmental Sensing ◽  
Regulatory Systems ◽  
Two Component

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

2011 ◽  
Vol 56 (2) ◽  
pp. 1019-1030 ◽  
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.

scholarly journals Novel roles for two-component regulatory systems in cytotoxicity and virulence-related properties in Pseudomonas aeruginosa

2018 ◽  
Vol 4 (1) ◽  
pp. 173-191 ◽  
Author(s):  
Shaan L. Gellatly ◽  
◽  
Manjeet Bains ◽  
Elena B.M. Breidenstein ◽  
Janine Strehmel ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Regulatory Systems ◽  
Two Component

scholarly journals A Second Operator Is Involved in Pseudomonas aeruginosa Elastase (lasB) Activation

1999 ◽  
Vol 181 (20) ◽  
pp. 6264-6270 ◽  
Author(s):  
Ronda M. Anderson ◽  
Chad A. Zimprich ◽  
Lynn Rust
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Homoserine Lactone ◽  
Sensing System ◽  
Synergistic Activation ◽  
Two Component ◽  
Operator Sequence ◽  
Quorum Sensing System ◽  
Pseudomonas Aeruginosa Elastase ◽  
Insertion Mutations

ABSTRACT Pseudomonas aeruginosa LasB elastase gene (lasB) transcription is controlled by the two-component quorum-sensing system of LasR, and the autoinducer, 3OC12-HSL (N-3-[oxododecanoyl]homoserine lactone). LasR and 3OC12-HSL-mediated lasBactivation requires a functional operator sequence (OP1) in thelasB promoter region. Optimal activation oflasB, however, requires a second sequence of 70% identity to OP1, named OP2, located 43 bp upstream of OP1. In this study, we used sequence substitutions and insertion mutations inlasBp-lacZ fusion plasmids to explore the role of OP2 in lasB activation. Our results demonstrate that (i) OP1 and OP2 synergistically mediate lasB activation; (ii) OP2, like OP1, responds to LasR and 3OC12-HSL; and (iii) the putative autoinducer-binding domain of LasR is not required for synergistic activation from OP1 and OP2.

scholarly journals Role of Divalent Cations in the Action of Polymyxin B and EDTA on Pseudomonas aeruginosa

1969 ◽  
Vol 59 (2) ◽  
pp. 263-274 ◽  
Author(s):  
M. R. W. BROWN ◽  
J. MELLING
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Divalent Cations ◽  
Polymyxin B

scholarly journals Impact of Two-Component Regulatory Systems PhoP-PhoQ and PmrA-PmrB on Colistin Pharmacodynamics in Pseudomonas aeruginosa

2012 ◽  
Vol 56 (6) ◽  
pp. 3453-3456 ◽  
Author(s):  
Neang S. Ly ◽  
Jenny Yang ◽  
Jurgen B. Bulitta ◽  
Brian T. Tsuji
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Pharmacodynamic Model ◽  
Maximal Effect ◽  
Wild Type ◽  
Content Type ◽  
Regulatory Systems ◽  
Two Component ◽  
Subinhibitory Concentrations

ABSTRACTThein vitropharmacodynamics of colistin againstPseudomonas aeruginosaPAO1 wild-type and isogenic knockout strains ofphoPandpmrAwere evaluated. Colistin killing at subinhibitory concentrations was greater against thephoPandpmrAmutants than the wild type within the first 8 h: the concentration that results in 50% of maximal effect (EC50) of thepmrAmutant (0.413 mg/liter) was less than that of the wild type (0.718 mg/liter) (P< 0.05). Anin vitropharmacodynamic model simulating human colistin regimens displayed initial killing followed by regrowth in thephoPmutant and gradual regrowth in thepmrAmutant and wild type.

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