Towards Innovative Antibacterial Correctors for Cystic Fibrosis Targeting the Lung Microbiome with a Multifunctional Effect.

Autor: Martina MG; Dipartimento di Scienze degli Alimenti e del Farmaco, Università degli Studi di Parma, Parco Area delle Scienze, 27/A, 43124, Parma, Italy., Sannio F; Dipartimento di Biotecnologie Mediche, Università degli Studi di Siena, Viale Bracci 16, 53100, Siena, Italy., Crespan E; Istituto di Genetica Molecolare, IGM-CNR 'Luigi Luca Cavalli-Sforza', Via Abbiategrasso 207, 27100, Pavi, Italy., Pavone M; Dipartimento di Scienze degli Alimenti e del Farmaco, Università degli Studi di Parma, Parco Area delle Scienze, 27/A, 43124, Parma, Italy., Simoncini A; Dipartimento di Scienze degli Alimenti e del Farmaco, Università degli Studi di Parma, Parco Area delle Scienze, 27/A, 43124, Parma, Italy., Barbieri F; Dipartimento di Scienze degli Alimenti e del Farmaco, Università degli Studi di Parma, Parco Area delle Scienze, 27/A, 43124, Parma, Italy., Perini C; Istituto di Genetica Molecolare, IGM-CNR 'Luigi Luca Cavalli-Sforza', Via Abbiategrasso 207, 27100, Pavi, Italy., Pesce E; U.O.C. Genetica Medica, IRCCS Istituto Giannina Gaslini, 16147, Genova, Italy., Maga G; Istituto di Genetica Molecolare, IGM-CNR 'Luigi Luca Cavalli-Sforza', Via Abbiategrasso 207, 27100, Pavi, Italy., Pedemonte N; U.O.C. Genetica Medica, IRCCS Istituto Giannina Gaslini, 16147, Genova, Italy., Docquier JD; Dipartimento di Biotecnologie Mediche, Università degli Studi di Siena, Viale Bracci 16, 53100, Siena, Italy.; Laboratoire de Bactériologie Moléculaire, Centre d'Ingénierie des Protéines, UR-InBioS, University of Liège, Allée du 6 Août, 4000, Liège, Belgium., Radi M; Dipartimento di Scienze degli Alimenti e del Farmaco, Università degli Studi di Parma, Parco Area delle Scienze, 27/A, 43124, Parma, Italy.
Jazyk: angličtina
Zdroj: ChemMedChem [ChemMedChem] 2022 Sep 05; Vol. 17 (17), pp. e202200277. Date of Electronic Publication: 2022 Jun 23.
DOI: 10.1002/cmdc.202200277
Abstrakt: Cystic fibrosis (CF) is a genetic disease caused by loss-of-function mutations in the CFTR gene, which codes for a defective ion channel. This causes an electrolyte imbalance and results in a spiral of negative effects on multiple organs, most notably the accumulation of thick mucus in the lungs, chronic respiratory tract infections and inflammation leading to pulmonary exacerbation and premature death. Progressive decline of lung function is mainly linked to persistent or recurring infections, mostly caused by bacteria, which require treatments with antibiotics and represent one of the major life-limiting factors in subjects with CF. Treatment of such a complex disease require multiple drugs with a consequent therapeutic burden and complications caused by drug-drug interactions and rapid emergence of bacterial drug resistance. We report herein our recent efforts in developing innovative multifunctional antibiotics specifically tailored to CF by a direct action on bacterial topoisomerases and a potential indirect effect on the pulmonary mucociliary clearance mediated by ΔF508-CFTR correction. The obtained results may pave the way for the development of a simplified therapeutic approach with a single agent acting as multifunctional Antibacterial-Corrector.
(© 2022 Wiley-VCH GmbH.)
Databáze: MEDLINE
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