International Journal of Molecular Sciences

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Special Issue Editor

Dr. Valeria Rachela Villella

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Guest Editor

1. Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, 80131 Napoli, Italy
2. CEINGE-Biotecnologie Avanzate Franco Salvatore, Via G. Salvatore, 486, 80145 Napoli, Italy
Interests: cystic fibrosis

Special Issue Information

Dear Colleagues,

Cystic Fibrosis (CF) is a rare disease caused by mutation of the gene encoding the CFTR protein. More than 2000 different mutations affecting it are known, the consequence of which always corresponds to an alteration/absence in the function of the CFTR. The quality of life of patients is greatly impaired, and although current therapies have significantly improved the lives of many patients with CF, still today, not all mutations are covered by effective treatment, making research the only way to reach a solution for everyone.

To date, the molecular mechanisms underlying this malfunction are not yet fully known, and although much progress has been made, many unknowns remain unaddressed. Several cellular mechanisms are altered in CF, each with a distinct effect on CFTR (dys)function, and many of the molecular pathways involved remain to be explored. The processing, trafficking and interactions of the CFTR protein represent an intrigued network of activities whose equilibrium, underlying its function, is finely ruled. This activates mechanisms that are still the subject of multiple studies on the effect of CFTR dysfunction.

The current modulators, which represent an excellent starting point for the resolution of the CFTR enigma, have a molecular and pathophysiological mechanism that is still open to functional hypotheses, and much research is still needed to arrive at a clear and precise answer.

The scope of this Special Issue focuses on, but is not limited to:

Molecular mechanisms and pathways of CFTR;
Molecular and protein interactions of CFTR;
Processing and trafficking of CFTR and involved proteins;
Molecular and functional studies on CFTR modulators;
New molecules and treatments;
Theratyping;
Pathogenesis of CF;
Alteration of cellular processes in cells and patients.

Dr. Valeria Rachela Villella
Guest Editor

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Keywords

CFTR protein interactions
molecular mechanism and processing
modulators
new drugs
pathogenesis and theratyping

Published Papers (2 papers)

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Research

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19 pages, 2292 KiB

Open AccessArticle

Insights into the Adolescent Cystic Fibrosis Airway Microbiome Using Shotgun Metagenomics

by Gillian McDermott, Aaron Walsh, Fiona Crispie, Susanna Frost, Peter Greally, Paul D. Cotter, Orla O’Sullivan and Julie Renwick

Int. J. Mol. Sci. 2024, 25(7), 3893; https://doi.org/10.3390/ijms25073893 - 31 Mar 2024

Viewed by 593

Abstract

Cystic fibrosis (CF) is an inherited genetic disorder which manifests primarily in airway disease. Recent advances in molecular technologies have unearthed the diverse polymicrobial nature of the CF airway. Numerous studies have characterised the genus-level composition of this airway community using targeted 16S rDNA sequencing. Here, we employed whole-genome shotgun metagenomics to provide a more comprehensive understanding of the early CF airway microbiome. We collected 48 sputum samples from 11 adolescents and children with CF over a 12-month period and performed shotgun metagenomics on the Illumina NextSeq platform. We carried out functional and taxonomic analysis of the lung microbiome at the species and strain levels. Correlations between microbial diversity measures and independent demographic and clinical variables were performed. Shotgun metagenomics detected a greater diversity of bacteria than culture-based methods. A large proportion of the top 25 most-dominant species were anaerobes. Samples dominated by Staphylococcus aureus and Prevotella melaninogenica had significantly higher microbiome diversity, while no CF pathogen was associated with reduced microbial diversity. There was a diverse resistome present in all samples in this study, with 57.8% agreement between shotgun metagenomics and culture-based methods for detection of resistance. Pathogenic sequence types (STs) of S. aureus, Pseudomonas aeruginosa, Haemophilus influenzae and Stenotrophomonas maltophilia were observed to persist in young CF patients, while STs of S. aureus were both persistent and shared between patients. This study provides new insight into the temporal changes in strain level composition of the microbiome and the landscape of the resistome in young people with CF. Shotgun metagenomics could provide a very useful one-stop assay for detecting pathogens, emergence of resistance and conversion to persistent colonisation in early CF disease. Full article

(This article belongs to the Special Issue Cystic Fibrosis: Molecular Pathogenesis, Diagnosis, and Treatment)

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Review

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16 pages, 528 KiB

Open AccessReview

The Effect of Complex Alleles of the CFTR Gene on the Clinical Manifestations of Cystic Fibrosis and the Effectiveness of Targeted Therapy

by Maria Krasnova, Anna Efremova, Artem Bukhonin, Elena Zhekaite, Tatiana Bukharova, Yuliya Melyanovskaya, Dmitry Goldshtein and Elena Kondratyeva

Int. J. Mol. Sci. 2024, 25(1), 114; https://doi.org/10.3390/ijms25010114 (registering DOI) - 21 Dec 2023

Viewed by 1036

Abstract

The authors of this article analyzed the available literature with the results of studying the prevalence of complex alleles of the CFTR gene among patients with cystic fibrosis, and their pathogenicity and influence on targeted therapy with CFTR modulators. Cystic fibrosis (CF) is a multisystemic autosomal recessive disease caused by a defect in the expression of the CFTR protein, and more than 2000 genetic variants are known. Clinically significant variants are divided into seven classes. Information about the frequency of complex alleles appears in a number of registers, along with the traditional presentation of data on genetic variants. Complex alleles (those with the presence of more than two nucleotide variants on one allele) can complicate the diagnosis of the disease, and change the clinical manifestations of cystic fibrosis and the response to treatment, since each variant in the complex allele can contribute to the functional activity of the CFTR protein, changing it both in terms of increasing and decreasing function. The role of complex alleles is often underestimated, and their frequency has not been studied. At the moment, characteristic frequently encountered complex alleles have been found for several populations of patients with cystic fibrosis, but the prevalence and pathogenicity of newly detected complex alleles require additional research. In this review, more than 35 complex alleles of the CFTR gene from existing research studies were analyzed, and an analysis of their influence on the manifestations of the disease and the effectiveness of CFTR modulators was also described. Full article

(This article belongs to the Special Issue Cystic Fibrosis: Molecular Pathogenesis, Diagnosis, and Treatment)

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