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19 pages, 4919 KiB

Open AccessArticle

Anti-Virulence Activity of the Cell-Free Supernatant of the Antarctic Bacterium Psychrobacter sp. TAE2020 against Pseudomonas aeruginosa Clinical Isolates from Cystic Fibrosis Patients

by Rosanna Papa, Gianluca Vrenna, Caterina D’Angelo, Angela Casillo, Michela Relucenti, Orlando Donfrancesco, Maria Michela Corsaro, Ersilia Vita Fiscarelli, Vanessa Tuccio Guarna Assanti, Maria Luisa Tutino, Ermenegilda Parrilli, Marco Artini and Laura Selan

Antibiotics 2021, 10(8), 944; https://doi.org/10.3390/antibiotics10080944 - 4 Aug 2021

Cited by 8 | Viewed by 2804

Abstract

Pseudomonas aeruginosa is an opportunistic pathogen often involved in airway infections of cystic fibrosis (CF) patients. Its pathogenicity is related to several virulence factors, such as biofilm formation, motility and production of toxins and proteases. The expression of these virulence factors is controlled [...] Read more.

Pseudomonas aeruginosa is an opportunistic pathogen often involved in airway infections of cystic fibrosis (CF) patients. Its pathogenicity is related to several virulence factors, such as biofilm formation, motility and production of toxins and proteases. The expression of these virulence factors is controlled by quorum sensing (QS). Thus, QS inhibition is considered a novel strategy for the development of antipathogenic compounds acting on specific bacterial virulence programs without affecting bacterial vitality. In this context, cold-adapted marine bacteria living in polar regions represent an untapped reservoir of biodiversity endowed with an interesting chemical repertoire. In this paper, we investigated the biological activity of a supernatant derived from a novel Antarctic bacterium (SN_TAE2020) against specific virulence factors produced by P. aeruginosa strains isolated from FC patients. Our results clearly show a reduction in pyocyanin and protease production in the presence of SN_TAE2020. Finally, SN_TAE2020 was also able to strongly affect swarming and swimming motility for almost all tested strains. Furthermore, the effect of SN_TAE2020 was investigated on biofilm growth and texture, captured by SEM analysis. In consideration of the novel results obtained on clinical strains, polar bacteria might represent potential candidates for the discovery of new compounds limiting P. aeruginosa virulence in CF patients. Full article

(This article belongs to the Special Issue The Treatment of Cystic Fibrosis (CF) Disease)

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8 pages, 751 KiB

Open AccessArticle

Elexacaftor–Tezacaftor–Ivacaftor Therapy for Cystic Fibrosis Patients with The F508del/Unknown Genotype

by Marika Comegna, Vito Terlizzi, Donatello Salvatore, Carmela Colangelo, Antonella Miriam Di Lullo, Immacolata Zollo, Giovanni Taccetti, Giuseppe Castaldo and Felice Amato

Antibiotics 2021, 10(7), 828; https://doi.org/10.3390/antibiotics10070828 - 7 Jul 2021

Cited by 18 | Viewed by 4590

Abstract

The new CFTR modulator combination, elexacaftor/tezacaftor/ivacaftor (Trikafta) was approved by the FDA in October 2019 for treatment of Cystic Fibrosis in patients 6 years of age or older who have at least one F508del mutation in one allele and a minimal-function or another [...] Read more.

The new CFTR modulator combination, elexacaftor/tezacaftor/ivacaftor (Trikafta) was approved by the FDA in October 2019 for treatment of Cystic Fibrosis in patients 6 years of age or older who have at least one F508del mutation in one allele and a minimal-function or another F508del mutation in the other allele. However, there is a group of patients, in addition to those with rare mutations, in which despite the presence of a F508del in one allele, it was not possible to identify any mutation in the other allele. To date, these patients are excluded from treatment with Trikafta in Italy, where the CF patients carrying F508del/unknown represent about 1.3% (71 patients) of the overall Italian CF patients. In this paper we show that the Trikafta treatment of nasal epithelial cells, derived from F508del/Unknown patients, results in a significant rescue of CFTR activity. Based on our findings, we think that the F508del/Unknown patients considered in this study could obtain clinical benefits from Trikafta treatment, and we strongly suggest their eligibility for this type of treatment. This study, adding further evidence in the literature, once again confirms the validity of functional studies on nasal cells in the cystic fibrosis theratyping and personalized medicine. Full article

(This article belongs to the Special Issue The Treatment of Cystic Fibrosis (CF) Disease)

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13 pages, 2068 KiB

Open AccessArticle

Evaluation of Aerosol Therapy during the Escalation of Care in a Model of Adult Cystic Fibrosis

by Elena Fernández Fernández, Mary Joyce, Andrew O’Sullivan and Ronan MacLoughlin

Antibiotics 2021, 10(5), 472; https://doi.org/10.3390/antibiotics10050472 - 21 Apr 2021

Cited by 13 | Viewed by 3296

Abstract

Lung disease is the main cause of morbidity and mortality in cystic fibrosis (CF). CF patients inhale antibiotics regularly as treatment against persistent bacterial infections. The goal of this study was to investigate the effect of clinical intervention on aerosol therapy during the [...] Read more.

Lung disease is the main cause of morbidity and mortality in cystic fibrosis (CF). CF patients inhale antibiotics regularly as treatment against persistent bacterial infections. The goal of this study was to investigate the effect of clinical intervention on aerosol therapy during the escalation of care using a bench model of adult CF. Droplet size analysis of selected antibiotics was completed in tandem with the delivered aerosol dose (% of total dose) assessments in simulations of various interventions providing oxygen supplementation or ventilatory support. Results highlight the variability of aerosolised dose delivery. In the homecare setting, the vibrating mesh nebuliser (VMN) delivered significantly more than the jet nebuliser (JN) (16.15 ± 0.86% versus 6.51 ± 2.15%). In the hospital setting, using VMN only, significant variability was seen across clinical interventions. In the emergency department, VMN plus mouthpiece (no supplemental oxygen) was seen to deliver (29.02 ± 1.41%) versus low flow nasal therapy (10 L per minute (LPM) oxygen) (1.81 ± 0.47%) and high flow nasal therapy (50 LPM oxygen) (3.36 ± 0.34%). In the ward/intensive care unit, non-invasive ventilation recorded 19.02 ± 0.28%, versus 22.64 ± 1.88% of the dose delivered during invasive mechanical ventilation. These results will have application in the design of intervention-appropriate aerosol therapy strategies and will be of use to researchers developing new therapeutics for application in cystic fibrosis and beyond. Full article

(This article belongs to the Special Issue The Treatment of Cystic Fibrosis (CF) Disease)

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Review

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26 pages, 2044 KiB

Open AccessReview

Polymicrobial Interactions in the Cystic Fibrosis Airway Microbiome Impact the Antimicrobial Susceptibility of Pseudomonas aeruginosa

by Emma Reece, Pedro H. de Almeida Bettio and Julie Renwick

Antibiotics 2021, 10(7), 827; https://doi.org/10.3390/antibiotics10070827 - 7 Jul 2021

Cited by 27 | Viewed by 4476

Abstract

Pseudomonas aeruginosa is one of the most dominant pathogens in cystic fibrosis (CF) airway disease and contributes to significant inflammation, airway damage, and poorer disease outcomes. The CF airway is now known to be host to a complex community of microorganisms, and polymicrobial [...] Read more.

Pseudomonas aeruginosa is one of the most dominant pathogens in cystic fibrosis (CF) airway disease and contributes to significant inflammation, airway damage, and poorer disease outcomes. The CF airway is now known to be host to a complex community of microorganisms, and polymicrobial interactions have been shown to play an important role in shaping P. aeruginosa pathogenicity and resistance. P. aeruginosa can cause chronic infections that once established are almost impossible to eradicate with antibiotics. CF patients that develop chronic P. aeruginosa infection have poorer lung function, higher morbidity, and a reduced life expectancy. P. aeruginosa adapts to the CF airway and quickly develops resistance to several antibiotics. A perplexing phenomenon is the disparity between in vitro antimicrobial sensitivity testing and clinical response. Considering the CF airway is host to a diverse community of microorganisms or ‘microbiome’ and that these microorganisms are known to interact, the antimicrobial resistance and progression of P. aeruginosa infection is likely influenced by these microbial relationships. This review combines the literature to date on interactions between P. aeruginosa and other airway microorganisms and the influence of these interactions on P. aeruginosa tolerance to antimicrobials. Full article

(This article belongs to the Special Issue The Treatment of Cystic Fibrosis (CF) Disease)

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24 pages, 1911 KiB

Open AccessFeature PaperReview

Systems Biology and Bile Acid Signalling in Microbiome-Host Interactions in the Cystic Fibrosis Lung

by David F. Woods, Stephanie Flynn, Jose A. Caparrós-Martín, Stephen M. Stick, F. Jerry Reen and Fergal O’Gara

Antibiotics 2021, 10(7), 766; https://doi.org/10.3390/antibiotics10070766 - 24 Jun 2021

Cited by 8 | Viewed by 3964

Abstract

The study of the respiratory microbiota has revealed that the lungs of healthy and diseased individuals harbour distinct microbial communities. Imbalances in these communities can contribute to the pathogenesis of lung disease. How these imbalances occur and establish is largely unknown. This review [...] Read more.

The study of the respiratory microbiota has revealed that the lungs of healthy and diseased individuals harbour distinct microbial communities. Imbalances in these communities can contribute to the pathogenesis of lung disease. How these imbalances occur and establish is largely unknown. This review is focused on the genetically inherited condition of Cystic Fibrosis (CF). Understanding the microbial and host-related factors that govern the establishment of chronic CF lung inflammation and pathogen colonisation is essential. Specifically, dissecting the interplay in the inflammation–pathogen–host axis. Bile acids are important host derived and microbially modified signal molecules that have been detected in CF lungs. These bile acids are associated with inflammation and restructuring of the lung microbiota linked to chronicity. This community remodelling involves a switch in the lung microbiota from a high biodiversity/low pathogen state to a low biodiversity/pathogen-dominated state. Bile acids are particularly associated with the dominance of Proteobacterial pathogens. The ability of bile acids to impact directly on both the lung microbiota and the host response offers a unifying principle underpinning the pathogenesis of CF. The modulating role of bile acids in lung microbiota dysbiosis and inflammation could offer new potential targets for designing innovative therapeutic approaches for respiratory disease. Full article

(This article belongs to the Special Issue The Treatment of Cystic Fibrosis (CF) Disease)

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41 pages, 1726 KiB

Open AccessReview

Treatment of Pulmonary Disease of Cystic Fibrosis: A Comprehensive Review

by Rosa María Girón Moreno, Marta García-Clemente, Layla Diab-Cáceres, Adrián Martínez-Vergara, Miguel Ángel Martínez-García and Rosa Mar Gómez-Punter

Antibiotics 2021, 10(5), 486; https://doi.org/10.3390/antibiotics10050486 - 23 Apr 2021

Cited by 21 | Viewed by 6675

Abstract

Cystic fibrosis (CF) is a genetic disease that causes absence or dysfunction of a protein named transmembrane conductance regulatory protein (CFTR) that works as an anion channel. As a result, the secretions of the organs where CFTR is expressed are very viscous, so [...] Read more.

Cystic fibrosis (CF) is a genetic disease that causes absence or dysfunction of a protein named transmembrane conductance regulatory protein (CFTR) that works as an anion channel. As a result, the secretions of the organs where CFTR is expressed are very viscous, so their functionality is altered. The main cause of morbidity is due to the involvement of the respiratory system as a result of recurrent respiratory infections by different pathogens. In recent decades, survival has been increasing, rising by around age 50. This is due to the monitoring of patients in multidisciplinary units, early diagnosis with neonatal screening, and advances in treatments. In this chapter, we will approach the different therapies used in CF for the treatment of symptoms, obstruction, inflammation, and infection. Moreover, we will discuss specific and personalized treatments to correct the defective gene and repair the altered protein CFTR. The obstacle for personalized CF treatment is to predict the drug response of patients due to genetic complexity and heterogeneity of uncommon mutations. Full article

(This article belongs to the Special Issue The Treatment of Cystic Fibrosis (CF) Disease)

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14 pages, 1331 KiB

Open AccessReview

Pseudomonas aeruginosa Resistance to Bacteriophages and Its Prevention by Strategic Therapeutic Cocktail Formulation

by Andrew Vaitekenas, Anna S. Tai, Joshua P. Ramsay, Stephen M. Stick and Anthony Kicic

Antibiotics 2021, 10(2), 145; https://doi.org/10.3390/antibiotics10020145 - 2 Feb 2021

Cited by 21 | Viewed by 5703

Abstract

Antimicrobial resistance poses a significant threat to modern healthcare as it limits treatment options for bacterial infections, particularly impacting those with chronic conditions such as cystic fibrosis (CF). Viscous mucus accumulation in the lungs of individuals genetically predisposed to CF leads to recurrent [...] Read more.

Antimicrobial resistance poses a significant threat to modern healthcare as it limits treatment options for bacterial infections, particularly impacting those with chronic conditions such as cystic fibrosis (CF). Viscous mucus accumulation in the lungs of individuals genetically predisposed to CF leads to recurrent bacterial infections, necessitating prolonged antimicrobial chemotherapy. Pseudomonas aeruginosa infections are the predominant driver of CF lung disease, and airway isolates are frequently resistant to multiple antimicrobials. Bacteriophages, or phages, are viruses that specifically infect bacteria and are a promising alternative to antimicrobials for CF P. aeruginosa infections. However, the narrow host range of P. aeruginosa-targeting phages and the rapid evolution of phage resistance could limit the clinical efficacy of phage therapy. A promising approach to overcome these issues is the strategic development of mixtures of phages (cocktails). The aim is to combine phages with broad host ranges and target multiple distinct bacterial receptors to prevent the evolution of phage resistance. However, further research is required to identify and characterize phage resistance mechanisms in CF-derived P. aeruginosa, which differ from their non-CF counterparts. In this review, we consider the mechanisms of P. aeruginosa phage resistance and how these could be overcome by an effective future phage therapy formulation. Full article

(This article belongs to the Special Issue The Treatment of Cystic Fibrosis (CF) Disease)

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9 pages, 992 KiB

Open AccessReview

Electrolyte and Acid-Base Disorders Triggered by Aminoglycoside or Colistin Therapy: A Systematic Review

by Martin Scoglio, Gabriel Bronz, Pietro O. Rinoldi, Pietro B. Faré, Céline Betti, Mario G. Bianchetti, Giacomo D. Simonetti, Viola Gennaro, Samuele Renzi, Sebastiano A. G. Lava and Gregorio P. Milani

Antibiotics 2021, 10(2), 140; https://doi.org/10.3390/antibiotics10020140 - 1 Feb 2021

Cited by 9 | Viewed by 3968

Abstract

Aminoglycoside or colistin therapy may alter the renal tubular function without decreasing the glomerular filtration rate. This association has never been extensively investigated. We conducted a systematic review of the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. Databases [...] Read more.

Aminoglycoside or colistin therapy may alter the renal tubular function without decreasing the glomerular filtration rate. This association has never been extensively investigated. We conducted a systematic review of the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. Databases searched included United States National Library of Medicine, Excerpta Medica, and Web of Science. For the final analysis, we evaluated 46 reports, published after 1960, describing 82 cases. A total of 286 electrolyte and acid-base disorders were reported. Hypomagnesemia, hypokalemia, and hypocalcemia were reported in more than three quarter of cases. Further disorders were, in decreasing order of frequency, metabolic alkalosis, hyponatremia, hypophosphatemia, hypouricemia, hypernatremia, and metabolic acidosis. Six electrolyte and acid-base disorders were reported in seven cases, five in 12 cases, four in 16 cases, three in 31 cases, two in 11 cases, and one in five cases. Laboratory features consistent with a loop of Henle/distal tubular dysfunction were noted in 56 (68%), with a proximal tubular dysfunction in three (3.7%), and with a mixed dysfunction in five (6.1%) cases. The laboratory abnormality was unclassified in the remaining 18 (22%) cases. Treatment with aminoglycosides or colistin may trigger a proximal tubular or, more frequently, a loop of Henle/distal tubular dysfunction. Full article

(This article belongs to the Special Issue The Treatment of Cystic Fibrosis (CF) Disease)

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