Tobramycin and FDA-Approved Iron Chelators Eliminate <i>Pseudomonas aeruginosa</i> Biofilms on Cystic Fibrosis Cells

Moreau‐Marquis, Sophie; O’Toole, George A.; Stanton, Bruce A.

doi:10.1165/rcmb.2008-0299oc

Cited by 190 publications

(182 citation statements)

References 58 publications

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“…Systemic inflammation and factors within the pulmonary microenvironment may modulate both neutrophil function and other aspects of innate immunity to impair host defence. Therapeutic strategies that target the pulmonary microenvironment, such as anti-proteases [47], or agents that modulate quorum sensing [48,49] or biofilm formation [50], may augment treatments that promote innate immune function [51]. …”

Section: Discussionmentioning

confidence: 99%

Cystic fibrosis neutrophils have normal intrinsic reactive oxygen species generation

McKeon¹,

Cadwallader²,

Idris³

et al. 2009

European Respiratory Journal

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Previous studies have identified abnormalities in the oxidative responses of the neutrophil in cystic fibrosis (CF), but it is unclear whether such changes relate to loss of membrane cystic fibrosis transmembrane conductance regulator (CFTR) or to the inflammatory environment present in this disease. The aim of the present study was to determine whether neutrophils from CF patients demonstrate an intrinsic abnormality of the respiratory burst.The respiratory burst activity of neutrophils isolated from stable DF508 homozygote CF patients and matched healthy controls was quantified by both chemiluminscence and cytochrome C reduction. Expression of NADPH oxidase components and CFTR was determined by Western blotting and RT-PCR.The oxidative output from neutrophils from CF in response to receptor-linked and particulate stimuli did not differ from that of controls. Expression of NADPH oxidase components was identical in CF and non-CF neutrophils. While low levels of CFTR mRNA could be identified in the normal human neutrophil, we were unable to detect CFTR protein in human neutrophil lysates or immunoprecipitates.CFTR has no role in controlling neutrophil oxidative activity; previously reported differences in neutrophil function between CF and non-CF subjects most likely relate to the inflammatory milieu from which the cells were isolated.

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Section: Discussionmentioning

confidence: 99%

Cystic fibrosis neutrophils have normal intrinsic reactive oxygen species generation

McKeon¹,

Cadwallader²,

Idris³

et al. 2009

European Respiratory Journal

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“…CFBE41o-cells, human airway epithelial cells homozygous for ⌬F508 (CFBE-⌬F508-CFTR), and their matched pair complemented with wt-CFTR (CFBE-wt-CFTR) have been used extensively as an experimental model to study CF (18,20,23,40); however, a comprehensive study examining the effect of P. aeruginosa on gene expression combined with cytokine/ chemokine profiles in these cells has not been undertaken. Thus the goal of this study was to examine the effect of P. aeruginosa on gene expression and cytokine/chemokine production in this matched pair of cells, which express the most common genotype in CF (⌬F508/⌬F508) with the ultimate goal of determining the utility of these cell lines as models to better understand the effects of the ⌬F508 mutation on the immune response to P. aeruginosa.…”

mentioning

confidence: 99%

Does the ΔF508-CFTR mutation induce a proinflammatory response in human airway epithelial cells?

Hampton

Ballok

Bomberger

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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In the clinical setting, mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene enhance the inflammatory response in the lung to Pseudomonas aeruginosa ( P. aeruginosa ) infection. However, studies on human airway epithelial cells in vitro have produced conflicting results regarding the effect of mutations in CFTR on the inflammatory response to P. aeruginosa, and there are no comprehensive studies evaluating the effect of P. aeruginosa on the inflammatory response in airway epithelial cells with the ΔF508/ΔF508 genotype and their matched CF cell line rescued with wild-type (wt)-CFTR. CFBE41o- cells (ΔF508/ΔF508) and CFBE41o- cells complemented with wt-CFTR (CFBE-wt-CFTR) have been used extensively as an experimental model to study CF. Thus the goal of this study was to examine the effect of P. aeruginosa on gene expression and cytokine/chemokine production in this pair of cells. P. aeruginosa elicited a more robust increase in cytokine and chemokine expression (e.g., IL-8, CXCL1, CXCL2 and TNF-α) in CFBE-wt-CFTR cells compared with CFBE-ΔF508-CFTR cells. These results demonstrate that CFBE41o- cells complemented with wt-CFTR mount a more robust inflammatory response to P. aeruginosa than CFBE41o-ΔF508/ΔF508-CFTR cells. Taken together with other published studies, our data demonstrate that there is no compelling evidence to support the view that mutations in CFTR induce a hyperinflammatory response in human airway epithelial cells in vivo . Although the lungs of patients with CF have abundant levels of proinflammatory cytokines and chemokines, because the lung is populated by immune cells and epithelial cells there is no way to know, a priori, whether airway epithelial cells in the CF lung in vivo are hyperinflammatory in response to P. aeruginosa compared with non-CF lung epithelial cells. Thus studies on human airway epithelial cell lines and primary cells in vitro that propose to examine the effect of mutations in CFTR on the inflammatory response to P. aeruginosa have uncertain clinical significance with regard to CF.

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“…In a different study, similar co-culture biofilms were formed by static incubation of P. aeruginosa and CF airway cells in the presence of arginine Moreau-Marquis, Redelman et al 2010). Importantly, in both systems, the antibiotic resistance of the co-culture biofilms was greatly increased compared to both planktonic bacteria and abiotic biofilms Moreau-Marquis, Bomberger et al 2008;Moreau-Marquis, O'Toole et al 2009). It was also discovered that the co-culture biofilms displayed a different genetic response to tobramycin treatment than biofilms formed on plastic .…”

Section: Biofilms Co-cultured With Airway Cellsmentioning

confidence: 93%

“…Indeed, treatment with iron chelators (desferasirox and desferoxamine) or gallium, which is a non-reducible mimic for iron, can interfere with P. aeruginosa metabolism, resulting in biofilm disruption and protection against P. aeruginosa infection in animal models (Kaneko, Thoendel et al 2007;DeLeon, Balldin et al 2009;Moreau-Marquis, O'Toole et al 2009). Inhibitors of P. aeruginosa T3SS have also been found (Aiello, Williams et al 2010).…”

Section: Newer Antimicrobial Strategiesmentioning

confidence: 99%

Pseudomonas aeruginosa Biofilm Formation in the CF Lung and Its Implications for Therapy

Anderson¹

2012

Cystic Fibrosis - Renewed Hopes Through Research

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Tobramycin and FDA-Approved Iron Chelators Eliminate Pseudomonas aeruginosa Biofilms on Cystic Fibrosis Cells

Cited by 190 publications

References 58 publications

Cystic fibrosis neutrophils have normal intrinsic reactive oxygen species generation

Cystic fibrosis neutrophils have normal intrinsic reactive oxygen species generation

Does the ΔF508-CFTR mutation induce a proinflammatory response in human airway epithelial cells?

Pseudomonas aeruginosa Biofilm Formation in the CF Lung and Its Implications for Therapy

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