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Myxinidin-Derived Peptide against Biofilms Caused by Cystic Fibrosis Emerging Pathogens

Rosa Bellavita1, Angela Maione2, Simone Braccia1

  • 1Department of Pharmacy, School of Medicine, University of Naples 'Federico II', Via Domenico Montesano 49, 80131 Naples, Italy.

International Journal of Molecular Sciences
|February 25, 2023
PubMed

Insights

A novel antimicrobial peptide, WMR-4, shows promise in combating chronic lung infections in cystic fibrosis (CF) patients by inhibiting and eradicating bacterial and fungal biofilms. This peptide offers a potential new strategy against multidrug-resistant pathogens.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Biochemistry

Background:

  • Cystic fibrosis (CF) patients suffer from chronic lung infections caused by multidrug-resistant bacteria like *Pseudomonas aeruginosa*, *Achromobacter xylosoxidans*, and *Stenotrophomonas maltophilia*.
  • The unique environment of CF airways promotes the formation of resilient mixed biofilms, challenging conventional antibiotic treatments.
  • Antimicrobial peptides (AMPs) are emerging as a viable alternative due to their broad-spectrum activity and immunomodulatory properties.

Purpose of the Study:

  • To evaluate the efficacy of a serum-stable antimicrobial peptide, WMR-4, against *Candida albicans*, *S. maltophilia*, and *A. xylosoxidans* biofilms.
  • To investigate the potential of WMR-4 in both inhibiting and eradicating mono- and dual-species biofilms in vitro and in vivo.
  • To elucidate the mechanism of action of WMR-4 through biophysical characterization.

Main Methods:

  • Development of a serum-stable antimicrobial peptide (WMR-4).
  • In vitro and in vivo studies assessing WMR-4's ability to inhibit and eradicate biofilms of *C. albicans*, *S. maltophilia*, and *A. xylosoxidans*.
  • Gene expression analysis related to biofilm formation and quorum sensing.
  • Biophysical studies including lipopolysaccharide (LPS) interaction and liposome insertion assays.

Main Results:

  • WMR-4 demonstrated a greater capacity to inhibit than to eradicate mono- and dual-species biofilms.
  • Gene expression analysis revealed downregulation of key genes involved in biofilm formation and quorum sensing.
  • Biophysical data indicated strong interaction of WMR-4 with LPS and insertion into membranes of Gram-negative bacteria and *Candida*.

Conclusions:

  • The antimicrobial peptide WMR-4 exhibits significant potential for therapeutic applications against challenging biofilms in chronic CF lung infections.
  • WMR-4's mechanism involves membrane disruption and interference with biofilm regulatory pathways.
  • Further development of AMPs like WMR-4 could offer novel treatment strategies for multidrug-resistant infections in CF patients.
Keywords:
Achromobacter xylosoxidansCandida albicansStenotrophomonas maltophiliaantibiofilm activityantimicrobial peptidescystic fibrosismembrane interactionpolymicrobial infections

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