Comparisons of Two Proteomic Analyses of Non-Mucoid and Mucoid Pseudomonas aeruginosa Clinical Isolates from a Cystic Fibrosis Patient

Abstract Objectives The cephalosporin nitric oxide (NO)-donor prodrug DEA-C3D (‘DiEthylAmin-Cephalosporin-3′-Diazeniumdiolate’) has been shown to initiate the dispersal of biofilms formed by the Pseudomonas aeruginosa laboratory strain PAO1. In this study, we investigated whether DEA-C3D disperses biofilms formed by clinical cystic fibrosis (CF) isolates of P. aeruginosa and its effect in combination with two antipseudomonal antibiotics, tobramycin and colistin, in vitro. Methods β-Lactamase-triggered release of NO from DEA-C3D was confirmed using a gas-phase chemiluminescence detector. MICs for P. aeruginosa clinical isolates were determined using the broth microdilution method. A crystal violet staining technique and confocal laser scanning microscopy were used to evaluate the effects of DEA-C3D on P. aeruginosa biofilms alone and in combination with tobramycin and colistin. Results DEA-C3D was confirmed to selectively release NO in response to contact with bacterial β-lactamase. Despite lacking direct, cephalosporin/β-lactam-based antibacterial activity, DEA-C3D was able to disperse biofilms formed by three P. aeruginosa clinical isolates. Confocal microscopy revealed that DEA-C3D in combination with tobramycin produces similar reductions in biofilm to DEA-C3D alone, whereas the combination with colistin causes near complete eradication of P. aeruginosa biofilms in vitro. Conclusions DEA-C3D is effective in dispersing biofilms formed by multiple clinical isolates of P. aeruginosa and could hold promise as a new adjunctive therapy to patients with CF.

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Serial isolates of Pseudomonas aeruginosa from a cystic fibrosis patient have identical pilin sequences.

Infection and Immunity ◽

10.1128/iai.56.3.665-672.1988 ◽

1988 ◽

Vol 56 (3) ◽

pp. 665-672 ◽

Cited By ~ 21

Author(s):

B L Pasloske ◽

A M Joffe ◽

Q Sun ◽

K Volpel ◽

W Paranchych ◽

...

Keyword(s):

Cystic Fibrosis ◽

Pseudomonas Aeruginosa ◽

Cystic Fibrosis Patient

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Chronic infection sustained by a Pseudomonas aeruginosa High-Risk clone producing the VIM-1 metallo-β-lactamase in a cystic fibrosis patient after lung transplantation

Journal of Cystic Fibrosis ◽

10.1016/j.jcf.2018.01.007 ◽

2018 ◽

Vol 17 (4) ◽

pp. 470-474

Author(s):

Simona Pollini ◽

Claudia Mugnaioli ◽

Daniela Dolce ◽

Silvia Campana ◽

Anna Silvia Neri ◽

...

Keyword(s):

Cystic Fibrosis ◽

Pseudomonas Aeruginosa ◽

High Risk ◽

Lung Transplantation ◽

Cystic Fibrosis Patient ◽

Chronic Infection

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Complete Genome Sequence of Pseudomonas aeruginosa Strain AA2 (LMG 27630), an Early Isolate Recovered from the Airway of a German Cystic Fibrosis Patient

Microbiology Resource Announcements ◽

10.1128/mra.00526-20 ◽

2020 ◽

Vol 9 (26) ◽

Author(s):

Andrea Sass ◽

Tom Coenye

Keyword(s):

Cystic Fibrosis ◽

Pseudomonas Aeruginosa ◽

Respiratory Tract ◽

Cystic Fibrosis Patient ◽

Genome Sequence ◽

Complete Genome Sequence ◽

Opportunistic Pathogen ◽

Content Type ◽

Airway Infections ◽

Early Isolate

ABSTRACT Pseudomonas aeruginosa is an opportunistic pathogen that is able to cause various infections, including airway infections in cystic fibrosis patients. Here, we present the complete closed and annotated genome sequence of P. aeruginosa AA2, an isolate obtained early during infection of the respiratory tract of a German cystic fibrosis patient.

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Rapid Emergence of Resistance to Linezolid and Mutator Phenotypes in Staphylococcus aureus Isolates from an Adult Cystic Fibrosis Patient

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01392-13 ◽

2013 ◽

Vol 57 (10) ◽

pp. 5186-5188 ◽

Cited By ~ 11

Author(s):

Asmaa Tazi ◽

Jeanne Chapron ◽

Gerald Touak ◽

Magalie Longo ◽

Dominique Hubert ◽

...

Keyword(s):

Cystic Fibrosis ◽

Staphylococcus Aureus ◽

Cystic Fibrosis Patient ◽

Therapeutic Option ◽

Clinical Isolates ◽

23S Rrna ◽

Mutator Phenotype ◽

Content Type ◽

Emergence Of Resistance ◽

Rapid Emergence

ABSTRACTLinezolid has emerged as an important therapeutic option for the treatment ofStaphylococcus aureusin patients with cystic fibrosis. We report the rapid emergence, upon treatment with linezolid, of linezolid-resistantS. aureusclinical isolates through the accumulation of resistance-associated 23S rRNA mutations, together with acquisition of an altered mutator phenotype.

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Draft genome sequence of an aminoglycoside-resistant RmtG-producing Pseudomonas aeruginosa ST235 isolated from a cystic fibrosis patient

Journal of Global Antimicrobial Resistance ◽

10.1016/j.jgar.2016.11.005 ◽

2017 ◽

Vol 8 ◽

pp. 106-107 ◽

Cited By ~ 2

Author(s):

Maria Fernanda C. Bueno ◽

Gabriela Rodrigues Francisco ◽

Louise Cerdeira ◽

Susan Ienne ◽

Tiago A. Souza ◽

...

Keyword(s):

Cystic Fibrosis ◽

Pseudomonas Aeruginosa ◽

Cystic Fibrosis Patient ◽

Genome Sequence ◽

Draft Genome ◽

Draft Genome Sequence

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Efficacy and Safety of Liposomal Clarithromycin and Its Effect on Pseudomonas aeruginosa Virulence Factors

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00235-13 ◽

2013 ◽

Vol 57 (6) ◽

pp. 2694-2704 ◽

Cited By ~ 61

Author(s):

Mai Alhajlan ◽

Moayad Alhariri ◽

Abdelwahab Omri

Keyword(s):

Cystic Fibrosis ◽

Pseudomonas Aeruginosa ◽

Virulence Factors ◽

Biological Fluid ◽

Free Drug ◽

Clinical Isolates ◽

Epithelial Cell Line ◽

Efficacy And Safety ◽

Surface Charges ◽

Content Type

ABSTRACTWe investigated the efficacy and safety of liposomal clarithromycin formulations with different surface charges against clinical isolates ofPseudomonas aeruginosafrom the lungs of cystic fibrosis (CF) patients. The liposomal clarithromycin formulations were prepared by the dehydration-rehydration method, and their sizes were measured using the dynamic-light-scattering technique. Encapsulation efficiency was determined by microbiological assay, and the stabilities of the formulations in biological fluid were evaluated for a period of 48 h. The MICs and minimum bactericidal concentrations (MBCs) of free and liposomal formulations were determined withP. aeruginosastrains isolated from CF patients. Liposomal clarithromycin activity against biofilm-formingP. aeruginosawas compared to that of free antibiotic using the Calgary Biofilm Device (CBD). The effects of subinhibitory concentrations of free and liposomal clarithromycin on bacterial virulence factors and motility on agar were investigated on clinical isolates ofP. aeruginosa. The cytotoxicities of the liposome preparations and free drug were evaluated on a pulmonary epithelial cell line (A549). The average diameter of the formulations was >222 nm, with encapsulation efficiencies ranging from 5.7% to 30.4%. The liposomes retained more than 70% of their drug content during the 48-h time period. The highly resistant strains ofP. aeruginosabecame susceptible to liposome-encapsulated clarithromycin (MIC, 256 mg/liter versus 8 mg/liter;P< 0.001). Liposomal clarithromycin reduced the bacterial growth within the biofilm by 3 to 4 log units (P< 0.001), significantly attenuated virulence factor production, and reduced bacterial twitching, swarming, and swimming motilities. The clarithromycin-entrapped liposomes were less cytotoxic than the free drug (P< 0.001). These data indicate that our novel formulations could be a useful strategy to enhance the efficacy of clarithromycin against resistantP. aeruginosastrains that commonly affect individuals with cystic fibrosis.

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