Pseudomonas aeruginosa isolates from cystic fibrosis patients induce neutrophil extracellular traps with different morphologies that could correlate with their disease severity

Martínez-Alemán, S.; Bustamante, Adriana; Jimenez-Valdes, Rocio J.; González, Gloria M.; Sánchez-González, Alejandro

doi:10.1016/j.ijmm.2020.151451

Cited by 13 publications

(12 citation statements)

References 45 publications

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“…Biofilm formation is a critical attribute of P. aeruginosa in being a successful nosocomial pathogen and it is also an important hallmark of chronic bacterial persistence. This may be observed in dental caries on the tooth surfaces [85,86], in skin and soft tissue infections [52], in infections of the middle ear [87], catheter-associated infections [19], pneumonia, and in the lungs of CF patients [88]. In the latter case, P. aeruginosa is able to survive and avoid clearance (withstanding the immune response and the subsequent administration of antimicrobials) in the respiratory and conductive zone of the lungs [89,90].…”

Section: Biofilm Formationmentioning

confidence: 99%

“…It has been noted by several publications that the minimum inhibitory concentrations (MICs) of bacteria inside the biofilm may be 10-10,000 times higher, compared to planktonic cells [75][76][77][78][79]83,84,[88][89][90]. On one hand, the secreted extracellular matrix significantly hinders the diffusion of the antibiotic molecules to effectively reach the bacterial targets (pharmacokinetic barrier); in addition to this, bacteria residing in the deeper layers of the biofilm will adapt to a differentiated metabolic state [75][76][77][78][79]83,84,[88][89][90]. It must be noted that the inhibition of bacterial growth is mechanistically distinct from bacterial killing, and antimicrobials (even in effective doses) may not kill cells inside a biofilm.…”

Section: Biofilm Formationmentioning

confidence: 99%

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It’s Not Easy Being Green: A Narrative Review on the Microbiology, Virulence and Therapeutic Prospects of Multidrug-Resistant Pseudomonas aeruginosa

2021

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Pseudomonas aeruginosa is the most frequent cause of infection among non-fermenting Gram-negative bacteria, predominantly affecting immunocompromised patients, but its pathogenic role should not be disregarded in immunocompetent patients. These pathogens present a concerning therapeutic challenge to clinicians, both in community and in hospital settings, due to their increasing prevalence of resistance, and this may lead to prolonged therapy, sequelae, and excess mortality in the affected patient population. The resistance mechanisms of P. aeruginosa may be classified into intrinsic and acquired resistance mechanisms. These mechanisms lead to occurrence of resistant strains against important antibiotics—relevant in the treatment of P. aeruginosa infections—such as β-lactams, quinolones, aminoglycosides, and colistin. The occurrence of a specific resistotype of P. aeruginosa, namely the emergence of carbapenem-resistant but cephalosporin-susceptible (Car-R/Ceph-S) strains, has received substantial attention from clinical microbiologists and infection control specialists; nevertheless, the available literature on this topic is still scarce. The aim of this present review paper is to provide a concise summary on the adaptability, virulence, and antibiotic resistance of P. aeruginosa to a readership of basic scientists and clinicians.

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Section: Biofilm Formationmentioning

confidence: 99%

Section: Biofilm Formationmentioning

confidence: 99%

It’s Not Easy Being Green: A Narrative Review on the Microbiology, Virulence and Therapeutic Prospects of Multidrug-Resistant Pseudomonas aeruginosa

2021

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“…Early isolates induced significantly higher NET levels compared to corresponding late isolates [98]. Furthermore, MARTÍNEZ-ALEMÁN et al [102] found that CF isolates stratified by disease severity could induce different NET morphologies. Isolates from severe patients induced spread morphologies, whereas isolates from mild and moderate patients generated globular NET formation morphologies.…”

Section: Bacterial Infectionmentioning

confidence: 99%

Neutrophil extracellular traps in chronic lung disease: implications for pathogenesis and therapy

Keir

Chalmers

2022

Eur Respir Rev

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Neutrophilic inflammation has a key role in the pathophysiology of multiple chronic lung diseases. The formation of neutrophil extracellular traps (NETs) has emerged as a key mechanism of disease in neutrophilic lung diseases including asthma, COPD, cystic fibrosis and, most recently, bronchiectasis. NETs are large, web-like structures composed of DNA and anti-microbial proteins that are able to bind pathogens, prevent microbial dissemination and degrade bacterial virulence factors. The release of excess concentrations of proteases, antimicrobial proteins, DNA and histones, however, also leads to tissue damage, impaired mucociliary clearance, impaired bacterial killing and increased inflammation. A number of studies have linked airway NET formation with greater disease severity, increased exacerbations and overall worse disease outcomes across the spectrum of airway diseases. Treating neutrophilic inflammation has been challenging in chronic lung disease because of the delicate balance between reducing inflammation and increasing the risk of infections through immunosuppression. Novel approaches to suppressing NET formation or the associated inflammation are in development and represent an important therapeutic target. This review will discuss the relationship between NETs and the pathophysiology of cystic fibrosis, asthma, COPD and bronchiectasis, and explore the current and future development of NET-targeting therapies.

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“…65 Numerous studies have found that P. aeruginosa can mediate NETosis through multiple stimulants including LPS, flagellum, and release of virulence factors. [119][120][121][122] The induction of NET formation gives P. aeruginosa a survival advantage, as NET formation inhibits and kills competitor microorganisms, while P. aeruginosa persists due to an ability to degrade NETs and a resistance to killing. [123][124][125] The induction and evasion of NETs is not limited to P. aeruginosa.…”

Section: Airway Infection Bacterial Infectionmentioning

confidence: 99%

Pathophysiology of Bronchiectasis

Keir

Chalmers

2021

Semin Respir Crit Care Med

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Bronchiectasis is a complex, heterogeneous disorder defined by both a radiological abnormality of permanent bronchial dilatation and a clinical syndrome. There are multiple underlying causes including severe infections, mycobacterial disease, autoimmune conditions, hypersensitivity disorders, and genetic conditions. The pathophysiology of disease is understood in terms of interdependent concepts of chronic infection, inflammation, impaired mucociliary clearance, and structural lung damage. Neutrophilic inflammation is characteristic of the disease, with elevated levels of harmful proteases such as neutrophil elastase associated with worse outcomes. Recent data show that neutrophil extracellular trap formation may be the key mechanism leading to protease release and severe bronchiectasis. Despite the dominant of neutrophilic disease, eosinophilic subtypes are recognized and may require specific treatments. Neutrophilic inflammation is associated with elevated bacterial loads and chronic infection with organisms such as Pseudomonas aeruginosa. Loss of diversity of the normal lung microbiota and dominance of proteobacteria such as Pseudomonas and Haemophilus are features of severe bronchiectasis and link to poor outcomes. Ciliary dysfunction is also a key feature, exemplified by the rare genetic syndrome of primary ciliary dyskinesia. Mucus symptoms arise through goblet cell hyperplasia and metaplasia and reduced ciliary function through dyskinesia and loss of ciliated cells. The contribution of chronic inflammation, infection, and mucus obstruction leads to progressive structural lung damage. The heterogeneity of the disease is the most challenging aspect of management. An understanding of the pathophysiology of disease and their biomarkers can help to guide personalized medicine approaches utilizing the concept of “treatable traits.”

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Pseudomonas aeruginosa isolates from cystic fibrosis patients induce neutrophil extracellular traps with different morphologies that could correlate with their disease severity

Cited by 13 publications

References 45 publications

It’s Not Easy Being Green: A Narrative Review on the Microbiology, Virulence and Therapeutic Prospects of Multidrug-Resistant Pseudomonas aeruginosa

It’s Not Easy Being Green: A Narrative Review on the Microbiology, Virulence and Therapeutic Prospects of Multidrug-Resistant Pseudomonas aeruginosa

Neutrophil extracellular traps in chronic lung disease: implications for pathogenesis and therapy

Pathophysiology of Bronchiectasis

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