Antimicrobial Peptides SET-M33L and SET-M33L-PEG Are Promising Agents Against Strong Biofilm-Forming P. aeruginosa, Including Multidrug-Resistant Isolates

Alessio Fontanot; Peter D Croughs; Clelia Cortese; Adrianus C J M de Bruijn; Chiara Falciani; Alessandro Pini; Isabella Ellinger; Wendy W J Unger; John P Hays

doi:10.3390/antibiotics14070699

Antimicrobial Peptides SET-M33L and SET-M33L-PEG Are Promising Agents Against Strong Biofilm-Forming P. aeruginosa, Including Multidrug-Resistant Isolates

Antibiotics (Basel). 2025 Jul 11;14(7):699. doi: 10.3390/antibiotics14070699.

Authors

Alessio Fontanot^{1

2

3}, Peter D Croughs², Clelia Cortese⁴, Adrianus C J M de Bruijn¹, Chiara Falciani^{4

5}, Alessandro Pini^{4

5

6}, Isabella Ellinger³, Wendy W J Unger¹, John P Hays²

Affiliations

¹ Laboratory of Pediatrics, Department of Pediatrics, Sophia Children's Hospital, Erasmus University Medical Center (Erasmus MC), 3015 GD Rotterdam, The Netherlands.
² Department of Medical Microbiology & Infectious Diseases, Erasmus University Medical Center (Erasmus MC), 3015 GD Rotterdam, The Netherlands.
³ Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria.
⁴ Department of Medical Biotechnology, University of Siena, via A. Moro 2, 53100 Siena, Italy.
⁵ SetLance srl, via Fiorentina 1, 53100 Siena, Italy.
⁶ Clinical Pathology Unit, Santa Maria alle Scotte Hospital, Viale M. Bracci, 53100 Siena, Italy.

Abstract

Background: The antimicrobial peptides (AMPs) SET-M33L and SET-M33L-PEG were investigated against 10 clinical isolates of P. aeruginosa. Methods: Their minimum inhibitory concentrations (MICs), minimum bactericidal concentrations (MBCs), and minimum biofilm inhibitory concentrations (MBICs) were evaluated against tobramycin, ceftazidime, and polymyxin B. Results: MICs and MBCs were 7- to 100-fold lower than tobramycin, and 10- to 300-fold lower than ceftazidime. Fractional inhibitory concentration (FIC) indices showed an additive effect, while fractional bactericidal concentration (FBC) indices showed synergistic effects (FBC < 0.5) for most isolates. Conclusion: SET-M33L and SET-M33L-PEG are promising antimicrobial agents against strong biofilm-forming P. aeruginosa, including MDR isolates.

Keywords: Pseudomonas aeruginosa; SET-M33L; SET-M33L-PEG; antimicrobial peptides; biofilm; multidrug resistance.

Grants and funding

101073263/Horizon Europe MSCA