Synergistic effects of antibiotics and fucoidan on dual-species Staphylococcus aureus and Acinetobacter baumannii biofilm in diabetic rat wound models.

Abstract

Chronic diabetic wounds are often complicated by biofilm-forming, antibiotic-resistant pathogens such as Staphylococcus aureus and Acinetobacter baumannii, which delay healing. This study evaluated the synergistic effects of gentamicin and imipenem in combination with fucoidan, a sulfated polysaccharide from brown seaweed, against dual-species biofilms in a diabetic rat wound model. Methicillin-resistant S. aureus (MRSA) strain 6 and A. baumannii strain 1, isolated from diabetic foot ulcers, were used to establish dual-species biofilms in vitro and in vivo. Excisional wounds were created in male Wistar rats with streptozocin-induced type II diabetes and infected with the biofilms. Rats received daily treatments of gentamicin, imipenem, their combination, or the triple combination with fucoidan. Outcomes assessed included bacterial load (CFU/g), biofilm formation, expression of biofilm-related genes (icaA and bap by real-time PCR), wound size, and histological healing parameters. The triple therapy demonstrated the strongest antibacterial effect, reducing bacterial load by more than 4 log₁₀ CFU/g compared to controls (p < 0.005). Real-time PCR revealed significant downregulation of icaA in S. aureus (threefold decrease) and bap in A. baumannii (fourfold decrease) relative to antibiotic-only groups (p < 0.005). Histology showed accelerated wound contraction and complete re-epithelialization by day 14 with the triple combination, whereas monotherapy or dual antibiotics led to delayed healing and persistent inflammation. Fucoidan enhances the efficacy of gentamicin and imipenem against biofilm-associated infections and promotes diabetic wound healing. This combinatorial approach offers a promising strategy for managing chronic, biofilm-infected wounds and combating antibiotic resistance.