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

2016 ◽  
Author(s):  
Ferrara S et al
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Small Rna ◽  
Molecular Targets ◽  
Regulatory Systems ◽  
New Frontier

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 PhoQ Mutations Promote Lipid A Modification and Polymyxin Resistance of Pseudomonas aeruginosa Found in Colistin-Treated Cystic Fibrosis Patients

2011 ◽  
Vol 55 (12) ◽  
pp. 5761-5769 ◽  
Author(s):  
Amanda K. Miller ◽  
Mark K. Brannon ◽  
Laurel Stevens ◽  
Helle Krogh Johansen ◽  
Sara E. Selgrade ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Lipid A ◽  
Loss Of Function ◽  
Content Type ◽  
Clinical Strains ◽  
Regulatory Systems ◽  
Polymyxin E ◽  
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 polymyxin resistance (MICs of 8 to 64 mg/liter) in laboratory and clinical strains of this organism. To explore the role of PhoPQ in high-level clinical polymyxin resistance,P. aeruginosastrains with colistin MICs > 512 mg/liter that had been isolated from cystic fibrosis patients treated with inhaled colistin (polymyxin E) were analyzed. Probable loss-of-functionphoQalleles found in these cystic fibrosis strains conferred resistance to polymyxin. Partial and complete suppressor mutations inphoPwere identified in some cystic fibrosis strains with resistance-conferringphoQmutations, suggesting that additional loci can be involved in polymyxin resistance inP. aeruginosa. Disruption of chromosomalphoQin the presence of an intactphoPallele stimulated 4-amino-l-arabinose addition to lipid A and induced transcription from the promoter of thepmrH(arnB) operon, consistent with the known role of this lipid A modification in polymyxin resistance. These results indicate thatphoQloss-of-function mutations can contribute to high-level polymyxin resistance in clinical strains ofP. aeruginosa.

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.

scholarly journals Role of quorum sensing by Pseudomonas aeruginosa in microbial keratitis and cystic fibrosis

Microbiology ◽  
2008 ◽  
Vol 154 (8) ◽  
pp. 2184-2194 ◽  
Author(s):  
M. D. P. Willcox ◽  
H. Zhu ◽  
T. C. R. Conibear ◽  
E. B. H. Hume ◽  
M. Givskov ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Microbial Keratitis

Characterization by pyocine typing and serotyping of oral and sputum strains of Pseudomonas aeruginosa isolated from cystic fibrosis patients

1987 ◽  
Vol 33 (3) ◽  
pp. 221-225 ◽  
Author(s):  
Kunio Komiyama ◽  
Brian F. Habbick ◽  
Tom Martin ◽  
Satwant K. Tumber
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Oral Cavity ◽  
Buccal Mucosa ◽  
Single Strain ◽  
Ecological Sites ◽  
Dental Plaques ◽  
Different Strains

Oral and sputum isolates of Pseudomonas aeruginosa in patients with cystic fibrosis were investigated. Of the 17 patients studied, 12 patients (71%) yielded both mucoid and nonmucoid variants of Pseudomonas aeruginosa from sputum and (or) various oral ecological sites, such as buccal mucosa, tongue dorsum, dental plaques, and saliva. A total of 51 strains of mucoid and nonmucoid Pseudomonas aeruginosa were isolated from these patients and were phenotypically characterized by both pyocine typing and serotyping. Five patients (42%) were colonized or infected by a single strain of Pseudomonas aeruginosa, whereas 7 patients (58%) were cocolonized or coinfected by two or more phenotypically different strains of Pseudomonas aeruginosa. To understand the mechanisms involved in Pseudomonas aeruginosa colonization, it may be necessary to identify multiple isolates of Pseudomonas aeruginosa not only from the sputum but also from the various oral ecological sites and to further explore the role of the oral cavity in this colonization.

scholarly journals Small RNA and transcriptome sequencing reveal the role of miR-199a-3p in inflammatory processes in cystic fibrosis airways

2018 ◽  
Vol 245 (4) ◽  
pp. 410-420 ◽  
Author(s):  
Pauline Bardin ◽  
Emmeline Marchal-Duval ◽  
Florence Sonneville ◽  
Sabine Blouquit-Laye ◽  
Nathalie Rousselet ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Small Rna ◽  
Transcriptome Sequencing ◽  
Inflammatory Processes

scholarly journals 154* Assessing the role of lysogenic bacteriophages in a cystic fibrosis epidemic strain of Pseudomonas aeruginosa

2011 ◽  
Vol 10 ◽  
pp. S39
Author(s):  
J.L. Fothergill ◽  
A.-A. Lemieux ◽  
C.E. James ◽  
I. Kukavica-Ibrulj ◽  
G. Filion ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Epidemic Strain
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