1887

Journal of Medical Microbiology logo

Volume 71, Issue 12

Challenges and opportunities in the development of novel antimicrobial therapeutics for cystic fibrosis Open Access

Abstract

Chronic respiratory infection is the primary driver of mortality in individuals with cystic fibrosis (CF). Existing drug screening models utilised in preclinical antimicrobial development are unable to mimic the complex CF respiratory environment. Consequently, antimicrobials showing promising activity in preclinical models often fail to translate through to clinical efficacy in people with CF. Model systems used in CF anti-infective drug discovery and development range from antimicrobial susceptibility testing in nutrient broth, through to 2D and 3D tissue culture systems and models. No single model fully recapitulates every key aspect of the CF lung. To improve the outcomes of people with CF (PwCF) it is necessary to develop a set of preclinical models that collectively recapitulate the CF respiratory environment to a high degree of accuracy. Models must be validated for their ability to mimic aspects of the CF lung and associated lung infection, through evaluation of biomarkers that can also be assessed following treatment in the clinic. This will give preclinical models greater predictive power for identification of antimicrobials with clinical efficacy. The landscape of CF is changing, with the advent of modulator therapies that correct the function of the CFTR protein, while antivirulence drugs and phage therapy are emerging alternative treatments to chronic infection. This review discusses the challenges faced in current antimicrobial development pipelines, including the advantages and disadvantages of current preclinical models and the impact of emerging treatments.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): antimicrobial development , cystic fibrosis , host-pathogen interactions , infection models , Pseudomonas aeruginosa and therapeutics
Funding
This study was supported by the:
  • NIHR Academic Clinical Fellowship
    • Principle Award Recipient: FrostFreddy
  • Wellcome and the Royal Society (Award 204457/Z/16/Z)
    • Principle Award Recipient: DanielR Neill
  • Cystic Fibrosis Trust and Cystic Fibrosis Foundation (Award SRC022)
    • Principle Award Recipient: NotApplicable
  • NIHR Academic Clinical Fellowship
    • Principle Award Recipient: FrostFrederick
© 2022 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2022-12-21
2024-05-03
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http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.001643
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Challenges and opportunities in the development of novel antimicrobial therapeutics for cystic fibrosis
J. Med. Microbiol. 71, 001643 (2022); https://doi.org/10.1099/jmm.0.001643
/content/journal/jmm/10.1099/jmm.0.001643
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