The role of Psl in the failure to eradicate Pseudomonas aeruginosa biofilms in children with cystic fibrosis

AbstractThe exopolysaccharide Psl contributes to biofilm structure and antibiotic tolerance and may play a role in the failure to eradicate Pseudomonas aeruginosa from cystic fibrosis (CF) airways. The study objective was to determine whether there were any differences in Psl in P. aeruginosa isolates that were successfully eradicated compared to those that persisted, despite inhaled tobramycin treatment, in children with CF. Initial P. aeruginosa isolates were collected from children with CF undergoing eradication treatment, grown as biofilms and labeled with 3 anti-Psl monoclonal antibodies (Cam003/Psl0096, WapR001, WapR016) before confocal microscopy visualization. When grown as biofilms, P. aeruginosa isolates from children who failed antibiotic eradication therapy, had significantly increased Psl0096 binding compared to isolates from those who cleared P. aeruginosa. This was confirmed in P. aeruginosa isolates from the SickKids Eradication Cohort as well as the Early Pseudomonas Infection Control (EPIC) trial. Increased anti-Psl antibody binding was associated with bacterial aggregation and tobramycin tolerance. The biofilm matrix represents a potential therapeutic target to improve P. aeruginosa eradication treatment.

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

Microbiology ◽

10.1099/mic.0.2008/019281-0 ◽

2008 ◽

Vol 154 (8) ◽

pp. 2184-2194 ◽

Cited By ~ 51

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

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

Canadian Journal of Microbiology ◽

10.1139/m87-038 ◽

1987 ◽

Vol 33 (3) ◽

pp. 221-225 ◽

Cited By ~ 5

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.

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The role of suboptimal concentrations of nebulized tobramycin in driving antimicrobial resistance in Pseudomonas aeruginosa isolates in cystic fibrosis - an in vitro study

Respiratory Care ◽

10.4187/respcare.08671 ◽

2021 ◽

pp. respcare.08671

Author(s):

John E. Moore ◽

B. Cherie Millar ◽

Marika Ollman-Selinger ◽

Lisa Cambridge

Keyword(s):

Cystic Fibrosis ◽

Pseudomonas Aeruginosa ◽

Antimicrobial Resistance ◽

In Vitro Study ◽

Vitro Study

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An Overview of Infections in Cystic Fibrosis Airways and the Role of Environmental Conditions on Pseudomonas aeruginosa Biofilm Formation and Viability

Cystic Fibrosis in the Light of New Research ◽

10.5772/60897 ◽

2015 ◽

Cited By ~ 2

Author(s):

Cameron T. McDaniel ◽

Warunya Panmanee ◽

Daniel J. Hassett

Keyword(s):

Cystic Fibrosis ◽

Pseudomonas Aeruginosa ◽

Environmental Conditions ◽

Biofilm Formation

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Pseudomonas aeruginosa Requires the DNA-Specific Endonuclease EndA To Degrade Extracellular Genomic DNA To Disperse from the Biofilm

Journal of Bacteriology ◽

10.1128/jb.00059-19 ◽

2019 ◽

Vol 201 (18) ◽

Cited By ~ 9

Author(s):

Kathryn E. Cherny ◽

Karin Sauer

Keyword(s):

Pseudomonas Aeruginosa ◽

Biofilm Formation ◽

Genomic Dna ◽

Early Stage ◽

Content Type ◽

Biofilm Dispersion ◽

Biofilm Structure ◽

First Time ◽

Biofilm Matrix ◽

Dispersed Cells

ABSTRACT The dispersion of biofilms is an active process resulting in the release of planktonic cells from the biofilm structure. While much is known about the process of dispersion cue perception and the subsequent modulation of the c-di-GMP pool, little is known about subsequent events resulting in the release of cells from the biofilm. Given that dispersion coincides with void formation and an overall erosion of the biofilm structure, we asked whether dispersion involves degradation of the biofilm matrix. Here, we focused on extracellular genomic DNA (eDNA) due to its almost universal presence in the matrix of biofilm-forming species. We identified two probable nucleases, endA and eddB, and eddA encoding a phosphatase that were significantly increased in transcript abundance in dispersed cells. However, only inactivation of endA but not eddA or eddB impaired dispersion by Pseudomonas aeruginosa biofilms in response to glutamate and nitric oxide (NO). Heterologously produced EndA was found to be secreted and active in degrading genomic DNA. While endA inactivation had little effect on biofilm formation and the presence of eDNA in biofilms, eDNA degradation upon induction of dispersion was impaired. In contrast, induction of endA expression coincided with eDNA degradation and resulted in biofilm dispersion. Thus, released cells demonstrated a hyperattaching phenotype but remained as resistant to tobramycin as biofilm cells from which they egress, indicating EndA-dispersed cells adopted some but not all of the phenotypes associated with dispersed cells. Our findings indicate for the first time a role of DNase EndA in dispersion and suggest weakening of the biofilm matrix is a requisite for biofilm dispersion. IMPORTANCE The finding that exposure to DNase I impairs biofilm formation or leads to the dispersal of early stage biofilms has led to the realization of extracellular genomic DNA (eDNA) as a structural component of the biofilm matrix. However, little is known about the contribution of intrinsic DNases to the weakening of the biofilm matrix and dispersion of established biofilms. Here, we demonstrate for the first time that nucleases are induced in dispersed Pseudomonas aeruginosa cells and are essential to the dispersion response and that degradation of matrix eDNA by endogenously produced/secreted EndA is required for P. aeruginosa biofilm dispersion. Our findings suggest that dispersing cells mediate their active release from the biofilm matrix via the induction of nucleases.

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

Journal of Cystic Fibrosis ◽

10.1016/s1569-1993(11)60170-7 ◽

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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WS01-1 Effectiveness of IV compared to oral eradication therapy of Pseudomonas aeruginosa in cystic fibrosis: multicentre randomised controlled trial (TORPEDO-CF)

Journal of Cystic Fibrosis ◽

10.1016/s1569-1993(19)30117-1 ◽

2019 ◽

Vol 18 ◽

pp. S1 ◽

Cited By ~ 2

Author(s):

S.C. Langton Hewer ◽

A.R. Smyth ◽

A.P. Jones ◽

M. Brown ◽

H. Hickey ◽

...

Keyword(s):

Cystic Fibrosis ◽

Pseudomonas Aeruginosa ◽

Randomised Controlled Trial ◽

Controlled Trial ◽

Eradication Therapy ◽

Randomised Controlled

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Pseudomonas aeruginosa eradication therapy and risk of acquiring Aspergillus in young children with cystic fibrosis

Thorax ◽

10.1136/thoraxjnl-2018-211548 ◽

2019 ◽

Vol 74 (8) ◽

pp. 740-748 ◽

Cited By ~ 6

Author(s):

Sabariah Noor Harun ◽

Nicholas H G Holford ◽

Keith Grimwood ◽

Claire E Wainwright ◽

Stefanie Hennig

Keyword(s):

Cystic Fibrosis ◽

Pseudomonas Aeruginosa ◽

Young Children ◽

Bronchoalveolar Lavage ◽

Eradication Therapy ◽

Positive Culture ◽

Cross Sectional ◽

Cross Sectional Analysis ◽

Increased Risk ◽

Sectional Analysis

BackgroundWhile Aspergillus detection rates in adults, adolescents and older children with cystic fibrosis (CF) have increased, the risk of acquiring this fungal pathogen in young children is unknown.AimTo determine the risk and explanatory factors of acquiring Aspergillus in children with CF by age 5 years.MethodsCross-sectional analysis of clinical, bronchoalveolar lavage and treatment data from the Australasian Cystic Fibrosis Bronchoalveolar Lavage study was used to identify predictive factors for detecting Aspergillus at age 5 years. A parametric repeated time-to-event model quantitatively described the risk and factors associated with acquiring Aspergillus and Pseudomonas aeruginosa from birth until age 5 years.ResultsCross-sectional analysis found that the number of P. aeruginosa eradication courses increased the odds of detecting Aspergillus at age 5 years (OR 1.61, 95% CI 1.23 to 2.12). The median (IQR) age for the first P. aeruginosa positive culture was 2.38 (1.32–3.79) years and 3.69 (1.68–4.74) years for the first Aspergillus positive culture. The risk of P. aeruginosa and Aspergillus events changes with time after the first year of study entry. It also decreases for P. aeruginosa after completing P. aeruginosa eradication (HR 0.15, 95% CI 0.00 to 0.79), but increases for Aspergillus events (HR 2.75, 95% CI 1.45 to 5.41). The risk of acquiring both types of events increases after having had a previous event.ConclusionIn young children with CF, completing P. aeruginosa eradication therapy and previous Aspergillus events are associated with increased risk of acquiring Aspergillus.

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