Transcriptomic insights into biofilm dynamics and therapeutic targets in chronic wound infections (MIMET 107281)

Abstract

Chronic wound infections remain a significant clinical challenge, primarily due to the formation of bacterial biofilms that hinder healing and increase antimicrobial resistance. This review explores various studies focused on biofilm development, transcriptional responses, and therapeutic strategies for combating biofilm-associated infections. Using Pseudomonas aeruginosa PAO1 in ex vivo porcine skin wound models, RNA-seq analysis revealed key genes involved in biofilm formation, notably the lapA gene encoding alkaline phosphatase, which was upregulated, while denitrification pathway genes such as nirS were downregulated. Targeting these pathways through NO induction showed potential for biofilm disruption.

Novel biofilm-inhibiting strategies, including silver nanoparticles, lactoferrin, and exopolysaccharides, demonstrated antibacterial, anti-biofilm, and wound-healing effects. Additionally, metal-based nanozymes (Ru-procyanidin nanoparticles) and microneedle patches embedded with cerium/zinc composites emerged as promising solutions for oxidative stress reduction and bacterial elimination in diabetic wounds. Omics approaches, particularly transcriptomics and metabolomics, have further elucidated biofilm differentiation mechanisms and host-pathogen interactions.

Advanced detection methods such as electrochemical biosensors and peptide nucleic acid fluorescent in situ hybridization (PNA-FISH) have improved the identification of biofilm-associated infections. Furthermore, comparative analyses of mixed-species and single-species biofilms highlighted their differential impact on wound healing, with polybacterial biofilms causing more severe impairment.

These findings underscore the importance of integrating RNA-based diagnostics, molecular therapies, and novel biomaterials to enhance chronic wound management. Future research should focus on translating these insights into clinical applications for more effective biofilm-targeted treatments.