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Molecular Insight into Approaches against Cystic Fibrosis Infections

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: closed (20 March 2025) | Viewed by 4456

Special Issue Editor

Special Issue Information

Dear Colleagues,

Cystic fibrosis (CF) is a life-limiting autosomal recessive disorder caused by mutations in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR). Patients with cystic fibrosis suffer from problems in the respiratory system, pancreas, intestine and other organs, mainly related to increased mucus viscosity due to abnormal chlorine excretion. Lung disease is the main cause of reduced life expectancy and death in patients with CF. Moreover, because various bacteria can colonize the thick mucus, these patients mostly present with complications caused by infections in the respiratory tract, which are often difficult to eradicate. Indeed, the main pathogens, which include among other Staphylococcus aureus, Pseudomonas aeruginosa, Burkholderia cepacia complex, non-tuberculous Mycobacteria are usually naturally resistant to the antibiotics used in the clinic due to several factors, thus difficult to eradicate. Consequently, novel drugs as well as the development of alternative strategies (i.e., nitric oxide, antimicrobial peptides, phage therapy, vaccines, etc.) are urgently needed.

In this context, this Special Issue aims to collect original research as well as review articles covering all molecular aspects of research in the field of infections in Cystic Fibrosis.

This Special Issue is supervised by Dr. Chiarelli Laurent and assisted by our Topical Advisory Panel Member Giovanni Stelitano (University of Pavia).

Dr. Chiarelli Laurent
Guest Editor

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Keywords

  • cystic fibrosis
  • infections
  • multi-drug resistant pathogens
  • new drugs
  • anti-virulence compounds
  • phage therapy
  • vaccines

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Published Papers (2 papers)

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Review

18 pages, 1035 KiB  
Review
Exploring Proteases as Alternative Molecular Targets to Tackle Inflammation in Cystic Fibrosis Respiratory Infections
by Angela Sandri and Federico Boschi
Int. J. Mol. Sci. 2025, 26(5), 1871; https://doi.org/10.3390/ijms26051871 - 21 Feb 2025
Viewed by 707
Abstract
Cystic fibrosis (CF) is characterized by chronic respiratory infections and excessive inflammation, driven by both host- and pathogen-derived proteases. The dysregulated activity of proteolytic enzymes such as neutrophil elastase (NE), cathepsin G, and matrix metalloproteases (MMPs) degrades lung tissue, exacerbates airway remodeling, and [...] Read more.
Cystic fibrosis (CF) is characterized by chronic respiratory infections and excessive inflammation, driven by both host- and pathogen-derived proteases. The dysregulated activity of proteolytic enzymes such as neutrophil elastase (NE), cathepsin G, and matrix metalloproteases (MMPs) degrades lung tissue, exacerbates airway remodeling, and perpetuates inflammatory cycles. Concurrently, bacterial proteases from pathogens such as Pseudomonas aeruginosa and Staphylococcus aureus contribute to immune evasion and tissue destruction, compounding disease severity. Despite advances in antimicrobial and anti-inflammatory therapies, protease-driven lung damage remains a critical challenge. This review examines the dual role of host and bacterial proteases in CF pathophysiology, highlighting emerging protease-targeted therapies aimed at mitigating lung damage and inflammation. Strategies explored include the inhibition of NE, MMPs, and bacterial proteases, with a focus on innovative therapeutic approaches such as dual-function inhibitors, biologics, and advanced drug delivery systems. By restoring the protease–antiprotease balance, these interventions offer the potential to improve clinical outcomes and quality of life for CF patients. Full article
(This article belongs to the Special Issue Molecular Insight into Approaches against Cystic Fibrosis Infections)
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14 pages, 610 KiB  
Review
Phage Therapy: An Alternative Approach to Combating Multidrug-Resistant Bacterial Infections in Cystic Fibrosis
by Mario Cocorullo, Giovanni Stelitano and Laurent Robert Chiarelli
Int. J. Mol. Sci. 2024, 25(15), 8321; https://doi.org/10.3390/ijms25158321 - 30 Jul 2024
Cited by 2 | Viewed by 3207
Abstract
Patients with cystic fibrosis (CF) are prone to developing life-threatening lung infections with a variety of pathogens that are difficult to eradicate, such as Burkholderia cepacia complex (Bcc), Hemophilus influenzae, Mycobacterium abscessus (Mab), Pseudomonas aeruginosa, and Staphylococcus aureus [...] Read more.
Patients with cystic fibrosis (CF) are prone to developing life-threatening lung infections with a variety of pathogens that are difficult to eradicate, such as Burkholderia cepacia complex (Bcc), Hemophilus influenzae, Mycobacterium abscessus (Mab), Pseudomonas aeruginosa, and Staphylococcus aureus. These infections still remain an important issue, despite the therapy for CF having considerably improved in recent years. Moreover, prolonged exposure to antibiotics in combination favors the development and spread of multi-resistant bacteria; thus, the development of alternative strategies is crucial to counter antimicrobial resistance. In this context, phage therapy, i.e., the use of phages, viruses that specifically infect bacteria, has become a promising strategy. In this review, we aim to address the current status of phage therapy in the management of multidrug-resistant infections, from compassionate use cases to ongoing clinical trials, as well as the challenges this approach presents in the particular context of CF patients. Full article
(This article belongs to the Special Issue Molecular Insight into Approaches against Cystic Fibrosis Infections)
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