In Vivo Antimicrobial Activity of Nisin Z Against <i>S. aureus</i> and Polyurea Pharmadendrimer PURE<sub>G4</sub>OEI<sub>48</sub> Against <i>P. aeruginosa</i> from Diabetic Foot Infections

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, devel...

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Main Authors: Isa Serrano, Dalila Mil-Homens, Rita F. Pires, Vasco D. B. Bonifácio, Joana F. Guerreiro, Eva Cunha, Sofia S. Costa, Luís Tavares, Manuela Oliveira
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Antibiotics
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Online Access:https://www.mdpi.com/2079-6382/14/5/444
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Summary: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 (PURE<sub>G4</sub>OEI<sub>48</sub>) (antimicrobial polymer), and amlodipine (antihypertensive drug) was evaluated against <i>S. aureus</i> and <i>P. aeruginosa</i> 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 <i>Galleria mellonella</i> model by assessing the larvae survival and health index. Results: The results indicate that Nisin Z exhibited antibacterial activity against <i>S. aureus</i> in vivo, allowing larvae full survival, and no antibacterial activity against <i>P. aeruginosa</i>. Nisin Z may have reduced the antibacterial effectiveness of both PURE<sub>G4</sub>OEI<sub>48</sub> and amlodipine. PURE<sub>G4</sub>OEI<sub>48</sub> significantly increased the survival of the larvae infected with <i>P. aeruginosa</i>, while amlodipine showed no activity against both bacteria in vivo. Conclusions: These findings suggest that both Nisin Z and PURE<sub>G4</sub>OEI<sub>48</sub> 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 PURE<sub>G4</sub>OEI<sub>48</sub> in more complex models.
ISSN:2079-6382