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Repurposed Drugs as Alternative Strategy to Fight Biofilm-Associated 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 (31 May 2022) | Viewed by 2249

Special Issue Editors

Department of Medical, Oral and Biotechnological Sciences, Center for Advanced Studies and Technology (CAST), Gabriele d’Annunzio University of Chieti-Pescara, 66100 Chieti, Italy
Interests: biofilm formation; cystic fibrosis; lung infections; probiotics; antibiotic resistance; antimicrobial compounds; Pseudomonas aeruginosa; Stenotrophomonas maltophilia; bacterial pathogenesis; microbial cooperation
Special Issues, Collections and Topics in MDPI journals
Department of Medical, Oral, and Biotechnological Sciences, G. d’Annunzio University of Chieti-Pescara, 66100 Chieti, Italy
Interests: biofilm formation mechanisms; role of biofilm formation in the pathogenesis of cystic fibrosis lung infections; drug repurposing to identify new molecules with antibacterial activity; antibiofilm strategies
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

The treatment of biofilm-related infections (BRIs) is challenging, as sessile microorganisms are inherently tolerant/resistant to antibiotics compared with planktonic counterparts. This scenario raises the urgent need to develop new molecules that possibly target cells within the biofilm and avoid selecting resistant strains. However, the traditional drug discovery process is extremely expensive and long, requiring years of experimentations followed by extensive clinical trials.

An alternative approach recently proposed to reduce the drug discovery time frame is “drug repurposing”. This strategy is based on the use of known and approved drugs for a medical indication other than the one for which it was developed. It can also include the use of drugs that have reached phase II or III of clinical trials, demonstrating no efficacy for a particular indication but which have nevertheless demonstrated good safety. Since their toxicity and pharmacokinetic profiles have already been studied, “repurposed” drugs are allowed to bypass certain clinical trials, saving time and reducing costs. This strategy is a promising tool in the treatment of bacterial infections as many molecules have secondary mechanisms of action which allow them to be effective against many pathogens.

In this Special Issue, we warmly invite you to submit original contributions and/or review papers highlighting the potential of FDA-approved or previously discarded drugs to prevent biofilm formation and/or eradicate mature (preformed) biofilm formed by clinically relevant bacterial and fungal species. We also welcome articles focused on the development of drug delivery systems of repurposed drugs to improve their bioavailability and/or targeting to augment therapeutic outcomes in the treatment of BRIs (e.g., cystic fibrosis lung infections, recurrent urinary infections, infective endocarditis, device-related infections). Contributions demonstrating in vitro, in vivo, preclinical, or clinical evidence of drug repurposing and/or reformulation for BRI therapy will be welcomed. Since IJMS is a journal of molecular science, pure clinical studies will not be suitable, but clinical submissions with biomolecular experiments are welcomed. Furthermore, we encourage contributions focused on the exploration of repurposed drugs that synergize with common antibiotics/antifungals.

Dr. Arianna Pompilio
Dr. Giovanni Di Bonaventura
Guest Editors

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Keywords

  • drug repurposing
  • biofilm-related infections
  • adhesion
  • drug resistance
  • drug delivery
  • bioavailability
  • combination therapy
  • reformulation
  • drug discovery

Published Papers (1 paper)

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Research

24 pages, 2144 KiB  
Article
Giving Drugs a Second Chance: Antibacterial and Antibiofilm Effects of Ciclopirox and Ribavirin against Cystic Fibrosis Pseudomonas aeruginosa Strains
Int. J. Mol. Sci. 2022, 23(9), 5029; https://doi.org/10.3390/ijms23095029 - 30 Apr 2022
Cited by 6 | Viewed by 1864
Abstract
Drug repurposing is an attractive strategy for developing new antibacterial molecules. Herein, we evaluated the in vitro antibacterial, antibiofilm, and antivirulence activities of eight FDA-approved “non-antibiotic” drugs, comparatively to tobramycin, against selected Pseudomonas aeruginosa strains from cystic fibrosis patients. MIC and MBC values [...] Read more.
Drug repurposing is an attractive strategy for developing new antibacterial molecules. Herein, we evaluated the in vitro antibacterial, antibiofilm, and antivirulence activities of eight FDA-approved “non-antibiotic” drugs, comparatively to tobramycin, against selected Pseudomonas aeruginosa strains from cystic fibrosis patients. MIC and MBC values were measured by broth microdilution method. Time–kill kinetics was studied by the macro dilution method, and synergy studies were performed by checkerboard microdilution assay. The activity against preformed biofilms was measured by crystal violet and viable cell count assays. The effects on gene expression were studied by real-time quantitative PCR, while the cytotoxic potential was evaluated against IB3-1 bronchial CF cells. Ciclopirox, 5-fluorouracil, and actinomycin D showed the best activity against P. aeruginosa planktonic cells and therefore underwent further evaluation. Time–kill assays indicated actinomycin D and ciclopirox, contrarily to 5-fluorouracil and tobramycin, have the potential for bacterial eradication, although with strain-dependent efficacy. Ciclopirox was the most effective against the viability of the preformed biofilm. A similar activity was observed for other drugs, although they stimulate extracellular polymeric substance production. Ribavirin showed a specific antibiofilm effect, not dependent on bacterial killing. Exposure to drugs and tobramycin generally caused hyperexpression of the virulence traits tested, except for actinomycin D, which downregulated the expression of alkaline protease and alginate polymerization. Ciclopirox and actinomycin D revealed high cytotoxic potential. Ciclopirox and ribavirin might provide chemical scaffolds for anti-P. aeruginosa drugs. Further studies are warranted to decrease ciclopirox cytotoxicity and evaluate the in vivo protective effects. Full article
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