Novel Mouse Model of Chronic<i>Pseudomonas aeruginosa</i>Lung Infection Mimicking Cystic Fibrosis

Hoffmann, Nadine; Rasmussen, Trine Bernholdt; Jensen, Peter Østrup; Stub, C.; Hentzer, Morten; Molin, Søren; Ciofu, Oana; Givskov, Michael; Johansen, Helle Krogh; Høiby, Niels

doi:10.1128/iai.73.4.2504-2514.2005

Cited by 163 publications

(187 citation statements)

References 74 publications

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“…In a cystic fibrosis mouse model (utilizing Cftr Ϫ/Ϫ mice [322]), treatment with AZM reduced the bacterial load in lungs of mice, and gene expression of the QSregulated lasB gene was downregulated in vivo (323). AZM treatment also downregulated production and polymerization of alginate, which, combined with decreasing QS responses, was a major contribution to enhanced sensitivity to H 2 O 2 and complement and loss of viability in the stationary phase of growth.…”

Section: Antibiotics As Qs Inhibitorsmentioning

confidence: 99%

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

LaSarre

Federle

2013

Microbiol Mol Biol Rev

693

556

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SUMMARY Cell-cell communication, or quorum sensing, is a widespread phenomenon in bacteria that is used to coordinate gene expression among local populations. Its use by bacterial pathogens to regulate genes that promote invasion, defense, and spread has been particularly well documented. With the ongoing emergence of antibiotic-resistant pathogens, there is a current need for development of alternative therapeutic strategies. An antivirulence approach by which quorum sensing is impeded has caught on as a viable means to manipulate bacterial processes, especially pathogenic traits that are harmful to human and animal health and agricultural productivity. The identification and development of chemical compounds and enzymes that facilitate quorum-sensing inhibition (QSI) by targeting signaling molecules, signal biogenesis, or signal detection are reviewed here. Overall, the evidence suggests that QSI therapy may be efficacious against some, but not necessarily all, bacterial pathogens, and several failures and ongoing concerns that may steer future studies in productive directions are discussed. Nevertheless, various QSI successes have rightfully perpetuated excitement surrounding new potential therapies, and this review highlights promising QSI leads in disrupting pathogenesis in both plants and animals.

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Section: Antibiotics As Qs Inhibitorsmentioning

confidence: 99%

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

LaSarre

Federle

2013

Microbiol Mol Biol Rev

693

556

View full text Add to dashboard Cite

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“…Bacteria-laden agarose beads were prepared by adding 10% (vol/vol) of bacteria stock solution to sterile PBS. P. aeruginosa stock solution was prepared with a P. aeruginosa clinical isolate generously provided by Dr. Gordon, University of Saskatchewan (NH57388) (39). An aliquot of P. aeruginosa NH57388 was inoculated in 80 mL of TSB in a 2-L Erlenmeyer flask and incubated for 28 h at 37°C with shaking at 170 rpm.…”

Section: Methodsmentioning

confidence: 99%

Pseudomonas aeruginosa triggers CFTR-mediated airway surface liquid secretion in swine trachea

Luan

Campanucci

Nair

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Significance Cystic fibrosis (CF) is a genetic disorder caused by mutations in the gene encoding for the anion channel cystic fibrosis transmembrane conductance regulator (CFTR). Several organs are affected in CF, but most of the morbidity and mortality comes from lung disease caused by the failure to clear bacteria. Bacterial clearance depends on a layer of airway surface liquid (ASL) covering the airways, rich in antimicrobial compounds and mucins, that removes bacteria from the airway through mucociliary clearance. This study provides the first demonstration that inhalation of bacteria triggers CFTR-dependent ASL secretion. We suggest that this response to inhaled pathogens is an important but previously unknown part of the innate immune response that would be missing in CF patients, resulting in reduced bacterial killing and facilitating infection.

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“…P. aeruginosa is able to survive by switching to the biofilm mode of growth (Figures 3, 4), which provides tolerance to the inflammatory defense mechanism and antibiotic therapy. Biofilm adaptation also allows survival in the aerobic respiratory zone, the conductive zone of the lungs which contain anaerobic sputum, and the paranasal sinuses where the mucus also has a decreased oxygen concentration [2][3][35][36][37][38][39][40]. During the adaptation, mucoid (biofilm mode of growth) and non-mucoid phenotypes are split off due to mutations ( Figure 5, Table 3).…”

Section: Prophylaxis and Treatment Of P Aeruginosa Biofilms In Cf Lumentioning

confidence: 99%

The clinical impact of bacterial biofilms

Høiby¹,

Ciofu²,

Johansen³

et al. 2011

Int J Oral Sci

Self Cite

735

536

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Bacteria survive in nature by forming biofilms on surfaces and probably most, if not all, bacteria (and fungi) are capable of forming biofilms. A biofilm is a structured consortium of bacteria embedded in a self-produced polymer matrix consisting of polysaccharide, protein and extracellular DNA. Bacterial biofilms are resistant to antibiotics, disinfectant chemicals and to phagocytosis and other components of the innate and adaptive inflammatory defense system of the body. It is known, for example, that persistence of staphylococcal infections related to foreign bodies is due to biofilm formation. Likewise, chronic Pseudomonas aeruginosa lung infections in cystic fibrosis patients are caused by biofilm growing mucoid strains. Gradients of nutrients and oxygen exist from the top to the bottom of biofilms and the bacterial cells located in nutrient poor areas have decreased metabolic activity and increased doubling times. These more or less dormant cells are therefore responsible for some of the tolerance to antibiotics. Biofilm growth is associated with an increased level of mutations. Bacteria in biofilms communicate by means of molecules, which activates certain genes responsible for production of virulence factors and, to some extent, biofilm structure. This phenomenon is called quorum sensing and depends upon the concentration of the quorum sensing molecules in a certain niche, which depends on the number of the bacteria. Biofilms can be prevented by antibiotic prophylaxis or early aggressive antibiotic therapy and they can be treated by chronic suppressive antibiotic therapy. Promising strategies may include the use of compounds which can dissolve the biofilm matrix and quorum sensing inhibitors, which increases biofilm susceptibility to antibiotics and phagocytosis.

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Novel Mouse Model of ChronicPseudomonas aeruginosaLung Infection Mimicking Cystic Fibrosis

Cited by 163 publications

References 74 publications

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

Pseudomonas aeruginosa triggers CFTR-mediated airway surface liquid secretion in swine trachea

The clinical impact of bacterial biofilms

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