Author(s):
Serrano, Isa ; Mil-Homens, Dalila ; Pires, Rita F. ; Bonifácio, Vasco D. B. ; Guerreiro, Joana F. ; Cunha, Eva ; Costa, Sofia S. ; Tavares, Luís ; Oliveira, Manuela
Date: 2025
Persistent ID: http://hdl.handle.net/10362/188731
Origin: Repositório Institucional da UNL
Subject(s): Amlodipine; core–shell polycationic polyurea pharmadendrimer; diabetic foot infection; Galleria mellonella; Nisin Z; Pseudomonas aeruginosa; Staphylococcus aureus; Microbiology; Biochemistry; Pharmacology, Toxicology and Pharmaceutics(all); Microbiology (medical); Infectious Diseases; Pharmacology (medical); SDG 3 - Good Health and Well-being
Description
Funding Information: This research was funded by national funds from the Fundação para a Ciência e a Tecnologia (FCT) (Projects PTDC/SAUINF/28466/2017 and PTDC/MEC-ONC/29327/2017); by the FCT in the scope of CIISA–Centro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, Universidade de Lisboa (Project UIDB/00276/2020), and Laboratório Associado para Ciência Animal e Veterinária (LA/P/0059/2020—AL4AnimalS); by the FCT in the scope of the Research Unit Institute for Bioengineering and Biosciences (iBB) (projects UIDB/04565/2020 and UIDP/04565/2020), and the Associate Laboratory Institute for Health and Bioeconomy (i4HB) (project LA/P/0140/2020); by the FCT in the scope of the Global Health and Tropical Medicine (GHTM) (project UID/04413/2020), and the Associate Laboratory in Translation and Innovation Towards Global Health (LA-REAL) (LA/P/0117/2020). Publisher Copyright: © 2025 by the authors.
Background/Objectives: Diabetic foot infections (DFIs) are commonly associated with frequent hospitalizations, limb amputations, and premature death due to the profile of the bacteria infecting foot ulcers. DFIs are generally colonized by a polymicrobial net of bacteria that grows in biofilms, developing an increased antimicrobial resistance to multiple antibiotics. DFI treatment is a hurdle, and the need to develop new therapies that do not promote resistance is urgent. Therefore, the antibacterial efficacy of Nisin Z (antimicrobial peptide), a core–shell polycationic polyurea pharmadendrimer (PUREG4OEI48) (antimicrobial polymer), and amlodipine (antihypertensive drug) was evaluated against S. aureus and P. aeruginosa isolated from a DFI and previously characterized. Methods: The antibacterial activity was analyzed in vitro by determining the minimal inhibitory concentration (MIC) and in vivo in a Galleria mellonella model by assessing the larvae survival and health index. Results: The results indicate that Nisin Z exhibited antibacterial activity against S. aureus in vivo, allowing larvae full survival, and no antibacterial activity against P. aeruginosa. Nisin Z may have reduced the antibacterial effectiveness of both PUREG4OEI48 and amlodipine. PUREG4OEI48 significantly increased the survival of the larvae infected with P. aeruginosa, while amlodipine showed no activity against both bacteria in vivo. Conclusions: These findings suggest that both Nisin Z and PUREG4OEI48 could potentially be used individually as adjunct treatments for mild DFIs. However, further studies are needed to confirm these findings and assess the potential toxicity and efficacy of PUREG4OEI48 in more complex models.
