Review
Immunology
Buqing Yi, Alexander H. Dalpke, Sebastien Boutin
Summary: The development of CFTR modulator therapies has significantly changed the treatment scheme of people with cystic fibrosis, but further research is needed to understand the effects of such modulation on the airway microbiome for managing airway infections effectively.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Carla M. P. Ribeiro, Matthew G. Higgs, Marianne S. Muhlebach, Matthew C. Wolfgang, Monica Borgatti, Ilaria Lampronti, Giulio Cabrini
Summary: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have provided a significant therapeutic advantage for people with cystic fibrosis (pwCF). However, these modulators face limitations in reducing chronic lung bacterial infection and inflammation, which are the main causes of respiratory damage and insufficiency in pwCF, especially in adults. This article revisits the debated issues of pulmonary bacterial infection and inflammatory processes in pwCF, highlighting the mechanisms favoring bacterial infection, the interplay between Pseudomonas aeruginosa and Staphylococcus aureus, and the cross-talk among bacteria, bronchial epithelial cells, and host immune defenses. The recent findings on the effect of CFTR modulators on bacterial infection and inflammation are also presented to identify potential therapeutic targets for respiratory pathology in pwCF.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Microbiology
Cristina Cigana, Ruggero Giannella, Alice Colavolpe, Beatriz Alcala-Franco, Giulia Mancini, Francesca Colombi, Chiara Bigogno, Ulla Bastrup, Giovanni Bertoni, Alessandra Bragonzi
Summary: CFTR modulators have direct antimicrobial properties and can enhance antibiotic activity against bacteria in cystic fibrosis patients. Bacterial infections can also impact the levels of CFTR modulators in the airways. Optimizing treatment regimens based on the interaction between CFTR modulators and bacterial infections may improve personalized treatment efficacy.
MICROBIOLOGY SPECTRUM
(2023)
Article
Cell Biology
Deborah M. Cholon, Matthew A. Greenwald, Matthew G. Higgs, Nancy L. Quinney, Susan E. Boyles, Suzanne L. Meinig, John T. Minges, Ashlesha Chaubal, Robert Tarran, Carla M. P. Ribeiro, Matthew C. Wolfgang, Martina Gentzsch
Summary: People with cystic fibrosis (pwCF) often suffer from chronic and recurring bacterial lung infections, even with CFTR modulator therapy. This study established a culture system with persistent Pseudomonas aeruginosa infection to examine the effects of CFTR modulators on CFTR function and bacterial persistence. The presence of P. aeruginosa increased CFTR mRNA, protein, and function, while CFTR modulators decreased bacterial burden. It highlights the importance of considering the effects of infection on CFTR rescue by CFTR modulators in evaluating and optimizing drug therapies for pwCF.
Review
Microbiology
Christina S. Thornton, Michael G. Surette
Summary: Cystic fibrosis is the most common and lethal genetic disease among the Caucasian population, leading to chronic airway inflammation and declining pulmonary function. Studies have shown a diverse community of anaerobic bacteria in CF patients' airways, potentially impacting disease progression through synergistic interaction with principal pathogens. Despite the understanding of this complex bacterial milieu, the specific roles of anaerobes in disease progression remain unclear.
JOURNAL OF CLINICAL MICROBIOLOGY
(2021)
Article
Microbiology
Xuerui Bao, Mona Bove, Tom Coenye
Summary: The high tolerance of Pseudomonas aeruginosa biofilms in respiratory tract infections in cystic fibrosis contributes to the failure of antibiotic therapy. This study identified carbon sources that could enhance the inhibiting and/or eradicating activity of tobramycin, ciprofloxacin, and ceftazidime against P. aeruginosa PAO1 biofilms. The mechanisms underlying the enhanced biofilm eradicating activity were strain-dependent.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Review
Immunology
Veronica Roxana Flores-Vega, Silvia Yalid Vargas-Roldan, Jose Luis Lezana-Fernandez, Ricardo Lascurain, Jose Ignacio Santos-Preciado, Roberto Rosales-Reyes
Summary: Cystic fibrosis is a genetic disease caused by a mutation in the cftr gene, affecting chloride ion and water transport and leading to bacterial infections in the lungs. Autophagy plays a crucial role in pathogen clearance, but P. aeruginosa and B. cenocepacia have strategies to evade this pathway, resulting in chronic inflammatory immune responses.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Immunology
Jonathan D. Cogen, Anna Faino, Frankline Onchiri, Lucas R. Hoffman, Matthew P. Kronman, David P. Nichols, Margaret Rosenfeld, Ronald L. Gibson
Summary: A retrospective cohort study found that there were no significant differences in respiratory and clinical outcomes between young patients with cystic fibrosis treated with one versus two intravenous antipseudomonal antibiotics for pulmonary exacerbations.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Biochemistry & Molecular Biology
Olaf Sommerburg, Susanne Haemmerling, S. Philipp Schneider, Juergen Okun, Claus-Dieter Langhans, Patricia Leutz-Schmidt, Mark O. Wielpuetz, Werner Siems, Simon Y. Graeber, Marcus A. Mall, Mirjam Stahl
Summary: CF patients receiving CFTR modulator therapy with LUM/IVA show substantial improvement in pulmonary inflammation and nutritional status, with a significant increase in plasma vitamin A concentration, highlighting the importance of monitoring for hypervitaminosis A.
Article
Biochemistry & Molecular Biology
Giovanni Di Bonaventura, Veronica Lupetti, Simone De Fabritiis, Alessandra Piccirilli, Annamaria Porreca, Marta Di Nicola, Arianna Pompilio
Summary: This study evaluated the antibacterial and antivirulence activities of eight FDA-approved non-antibiotic drugs and their effects on biofilm formation. Ciclopirox and actinomycin D showed the best antibacterial activity and were most effective against preformed biofilms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Medicine, Research & Experimental
Roberto Rosales-Reyes, Veronica Roxana Flores-Vega, Jose Luis Lezana-Fernandez, Jose Ignacio Santos-Preciado
Summary: Pseudomonas aeruginosa is a significant pathogen causing lung infections in patients with cystic fibrosis. Its increasing antibiotic resistance makes treatment challenging. Microbiology and whole genome sequencing are important tools for determining antimicrobial susceptibility and resistance as well as analyzing genomic variations. Molecular epidemiologic surveillance aids in developing better treatment strategies and controlling the spread of Pseudomonas aeruginosa variants.
ARCHIVES OF MEDICAL RESEARCH
(2022)
Article
Respiratory System
Scott D. Sagel, Umer Khan, Sonya L. Heltshe, John P. Clancy, Drucy Borowitz, Daniel Gelfond, Scott H. Donaldson, Antoinette Moran, Felix Ratjen, Jill M. VanDalfsen, Steven M. Rowe
Summary: The study evaluated the effectiveness of LUM/IVA treatment in children and adults with CF, revealing significant improvements in growth and reductions in sweat chloride over one year, while showing no statistically or clinically meaningful changes in lung function, hospitalization rates, or P. aeruginosa infection.
ANNALS OF THE AMERICAN THORACIC SOCIETY
(2021)
Article
Immunology
Jonathan D. Cogen, Frankline M. Onchiri, Nicole Mayer Hamblett, Ronald L. Gibson, Wayne J. Morgan, Margaret Rosenfeld
Summary: The study showed that prolonged use of oral antibiotics in children with cystic fibrosis increased the risk of acquiring Achromobacter xylosoxidans, while treatment with intravenous antibiotics was associated with an increased risk of acquiring multidrug-resistant Pseudomonas aeruginosa and MRSA.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Microbiology
Giovanni Di Bonaventura, Veronica Lupetti, Fabio Verginelli, Sara Giancristofaro, Rosemary Barbieri, Giovanni Gherardi, Arianna Pompilio
Summary: This study evaluated the antibacterial, antibiofilm, and antivirulence activities of apramycin compared to tobramycin against P. aeruginosa in cystic fibrosis patients. Apramycin showed better efficacy than tobramycin, without cytotoxicity to bronchial epithelial CF cells.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Nutrition & Dietetics
Aleksandra John, Joanna Gozdzik-Spychalska, Magdalena Durda-Masny, Wojciech Czainski, Natalia Pawlowska, Jolanta Wlizlo, Halina Batura-Gabryel, Anita Szwed
Summary: The study described the relationship between the prevalence of Pseudomonas aeruginosa (PA) and lung function, nutritional status, and gene mutation type in adult patients with cystic fibrosis (CF). The presence of PA was associated with lower FEV1% and BMI values. Severe gene mutation, undernutrition, and deterioration of lung function were linked to a higher probability of PA acquisition and resistance to antibiotic treatment.