Pexiganan in Combination with Nisin to Control Polymicrobial Diabetic Foot Infections

• Published in: Antibiotics (Basel) Vol. 9; no. 3; p. 128
• Main Authors: Gomes, Diana, Santos, Raquel, S Soares, Rui, Reis, Solange, Carvalho, Sandra, Rego, Pedro, C Peleteiro, Maria, Tavares, Luís, Oliveira, Manuela
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 20-03-2020; MDPI
• Subjects: 3d wound model; Antibacterial agents; Antibiotics; Antiinfectives and antibacterials; Antimicrobial activity; Antimicrobial agents; Antimicrobial peptides; biofilm; Biofilms; Collagen; Complications; Diabetes; Diabetes mellitus; Diabetic foot; diabetic foot infections; diabetic foot ulcers; Feet; Foot diseases; Gram-positive bacteria; Guar gum; Infections; Leg ulcers; Medical research; Microbial drug resistance; Microbial mats; Microorganisms; Morbidity; Multidrug resistance; Nisin; Peptides; pexiganan; Pseudomonas aeruginosa; Staphylococcus aureus; Staphylococcus infections; Strains (organisms); Three dimensional models; Ulcers; Wound healing; Portugal; diabetic foot infections; guar gum; nisin; pexiganan; 3D wound model; Antimicrobial peptides; biofilm; Pseudomonas aeruginosa; diabetic foot ulcers; Staphylococcus aureus
• ISSN: 2079-6382; 2079-6382
• DOI: 10.3390/antibiotics9030128

Diabetic foot ulcers (DFUs) are major complications of Diabetes
being responsible for significant morbidity and mortality. DFUs frequently become chronically infected by a complex community of bacteria, including multidrug-resistant and biofilm-producing strains of
and
. Diabetic foot infections (DFI) are often recalcitrant to conventional antibiotics and alternative treatment strategies are urgently needed. Antimicrobial Peptides (AMPs), such as pexiganan and nisin, have been increasingly investigated and reported as effective antimicrobial agents. Here, we evaluated the antibacterial potential of pexiganan and nisin used in combination (dual-AMP) to control the growth of planktonic and biofilm co-cultures of
and
clinical strains, co-isolated from a DFU. A DFU collagen three-dimensional (3D) model was used to evaluate the distribution and efficacy of AMPs locally delivered into the model. The concentration of pexiganan required to inhibit and eradicate both planktonic and biofilm-based bacterial cells was substantially reduced when used in combination with nisin. Moreover, incorporation of both AMPs in a guar gum delivery system (dual-AMP biogel) did not affect the dual-AMP antimicrobial activity. Importantly, the application of the dual-AMP biogel resulted in the eradication of the
strain from the model. In conclusion, data suggest that the local application of the dual-AMPs biogel constitutes a potential complementary therapy for the treatment of infected DFU.