scholarly journals Occurrence of Hypermutable Pseudomonas aeruginosa in Cystic Fibrosis Patients Is Associated with the Oxidative Stress Caused by Chronic Lung Inflammation

2005 ◽  
Vol 49 (6) ◽  
pp. 2276-2282 ◽  
Author(s):  
Oana Ciofu ◽  
Bente Riis ◽  
Tacjana Pressler ◽  
Henrik Enghusen Poulsen ◽  
Niels Høiby
Keyword(s):  
Oxidative Stress ◽  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Lung Inflammation ◽  
Bacterial Population ◽  
Lung Infection ◽  
Bacterial Dna ◽  
Increased Risk ◽  
Oxidized Guanine ◽  
Chronic Lung Infection

ABSTRACT Oxidative stress caused by chronic lung inflammation in patients with cystic fibrosis (CF) and chronic lung infection with Pseudomonas aeruginosa is characterized by the reactive oxygen species (ROS) liberated by polymorphonuclear leukocytes (PMNs). We formulated the hypothesis that oxidation of the bacterial DNA by ROS presents an increased risk for the occurrence of hypermutable P. aeruginosa. The occurrence of hypermutable P. aeruginosa isolates was investigated directly in the sputum of 79 CF patients and among 141 isolates collected from 11 CF patients (10 to 15 isolates/patient) collected from the 1st and up to the 25th year of their chronic lung infection. The level of oxidized guanine moiety 8-oxo-2′-deoxyguanosine (8-oxodG), which is a frequently investigated DNA oxidative lesion, was measured. Hypermutable P. aeruginosa isolates were found in the sputum bacterial population of 54.4% of the CF patients. The earliest mutator P. aeruginosa isolates were found after 5 years from the onset of the chronic lung infection, and once they were present in the CF lung, the prevalence increased with time. The hypermutable isolates were significantly more resistant to antipseudomonal antibiotics than nonhypermutable isolates (P ≤ 0.001). The level of 8-oxodG/106 deoxyguanosine (dG) was significantly higher in hypermutable P. aeruginosa isolates (87 ± 38) than in nonhypermutable P. aeruginosa isolates (59.4 ± 17) (P = 0.02), and an increase to 86.84 from 21.65 8-oxodG/106 dG was found after exposure of the reference strain PAO1 to activated PMNs. Our results suggest that the chronic PMN inflammation in the CF lung promotes oxidative stress and is associated with the occurrence of hypermutable bacteria in the lung. The hypermutable phenotype can associate with mutations that confer adaptation of the bacteria in the lung and persistence of the infection.

scholarly journals Draft Genome Sequence for Pseudomonas aeruginosa Strain PAO579, a Mucoid Derivative of PAO381

2012 ◽  
Vol 194 (23) ◽  
pp. 6617-6617 ◽  
Author(s):  
T. Ryan Withers ◽  
Shannon L. Johnson ◽  
Hongwei D. Yu
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Genome Sequence ◽  
Draft Genome ◽  
Opportunistic Pathogen ◽  
Lung Infection ◽  
Draft Genome Sequence ◽  
Content Type ◽  
Chronic Lung Infection

ABSTRACTPseudomonas aeruginosais an opportunistic pathogen that establishes a chronic lung infection in individuals afflicted with cystic fibrosis. Here, we announce the draft genome ofP. aeruginosastrain PAO579, an alginate-overproducing derivative of strain PAO381.

scholarly journals Evolution and diversification of Pseudomonas aeruginosa in the paranasal sinuses of cystic fibrosis children have implications for chronic lung infection

2011 ◽  
Vol 6 (1) ◽  
pp. 31-45 ◽  
Author(s):  
Susse Kirkelund Hansen ◽  
Martin Holm Rau ◽  
Helle Krogh Johansen ◽  
Oana Ciofu ◽  
Lars Jelsbak ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Paranasal Sinuses ◽  
Lung Infection ◽  
Chronic Lung Infection

scholarly journals Animal models of chronic lung infection with Pseudomonas aeruginosa: useful tools for cystic fibrosis studies

2008 ◽  
Vol 42 (4) ◽  
pp. 389-412 ◽  
Author(s):  
I Kukavica-Ibrulj ◽  
R C Levesque
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Animal Models ◽  
Pancreatic Insufficiency ◽  
Lung Infection ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Human Form ◽  
Cftr Protein ◽  
Chronic Lung Infection

Summary Cystic fibrosis (CF) is caused by a defect in the transmembrane conductance regulator (CFTR) protein that functions as a chloride channel. Dysfunction of the CFTR protein results in salty sweat, pancreatic insufficiency, intestinal obstruction, male infertility and severe pulmonary disease. In most patients with CF life expectancy is limited due to a progressive loss of functional lung tissue. Early in life a persistent neutrophylic inflammation can be demonstrated in the airways. The cause of this inflammation, the role of CFTR and the cause of lung morbidity by different CF-specific bacteria, mostly Pseudomonas aeruginosa, are not well understood. The lack of an appropriate animal model with multi-organ pathology having the characteristics of the human form of CF has hampered our understanding of the pathobiology and chronic lung infections of the disease for many years. This review summarizes the main characteristics of CF and focuses on several available animal models that have been frequently used in CF research. A better understanding of the chronic lung infection caused particularly by P. aeruginosa, the pathophysiology of lung inflammation and the pathogenesis of lung disease necessitates animal models to understand CF, and to develop and improve treatment.

scholarly journals Secretory IgA response against Pseudomonas aeruginosa in the upper airways and the link with chronic lung infection in cystic fibrosis

2017 ◽  
Vol 75 (6) ◽  
Author(s):  
Renan M. Mauch ◽  
Claudio L. Rossi ◽  
Talita B. Aiello ◽  
José D. Ribeiro ◽  
Antônio F. Ribeiro ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Lung Infection ◽  
Secretory Iga ◽  
Upper Airways ◽  
Iga Response ◽  
Chronic Lung Infection

scholarly journals Aerosolized Bovine Lactoferrin Counteracts Infection, Inflammation and Iron Dysbalance in A Cystic Fibrosis Mouse Model of Pseudomonas aeruginosa Chronic Lung Infection

2019 ◽  
Vol 20 (9) ◽  
pp. 2128 ◽  
Author(s):  
Antimo Cutone ◽  
Maria Stefania Lepanto ◽  
Luigi Rosa ◽  
Mellani Jinnett Scotti ◽  
Alice Rossi ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Genetic Disorder ◽  
Bacterial Load ◽  
Lung Infection ◽  
Multidrug Resistant ◽  
Bovine Lactoferrin ◽  
Lung Pathology ◽  
Iron Storage ◽  
Chronic Lung Infection

Cystic fibrosis (CF) is a genetic disorder affecting several organs including airways. Bacterial infection, inflammation and iron dysbalance play a major role in the chronicity and severity of the lung pathology. The aim of this study was to investigate the effect of lactoferrin (Lf), a multifunctional iron-chelating glycoprotein of innate immunity, in a CF murine model of Pseudomonas aeruginosa chronic lung infection. To induce chronic lung infection, C57BL/6 mice, either cystic fibrosis transmembrane conductance regulator (CFTR)-deficient (Cftrtm1UNCTgN(FABPCFTR)#Jaw) or wild-type (WT), were intra-tracheally inoculated with multidrug-resistant MDR-RP73 P. aeruginosa embedded in agar beads. Treatments with aerosolized bovine Lf (bLf) or saline were started five minutes after infection and repeated daily for six days. Our results demonstrated that aerosolized bLf was effective in significantly reducing both pulmonary bacterial load and infiltrated leukocytes in infected CF mice. Furthermore, for the first time, we showed that bLf reduced pulmonary iron overload, in both WT and CF mice. In particular, at molecular level, a significant decrease of both the iron exporter ferroportin and iron storage ferritin, as well as luminal iron content was observed. Overall, bLf acts as a potent multi-targeting agent able to break the vicious cycle induced by P. aeruginosa, inflammation and iron dysbalance, thus mitigating the severity of CF-related pathology and sequelae.

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