Tannic acid attenuates Pseudomonas aeruginosa virulence and accelerates healing of infected cutaneous wounds via transcriptome-revealed pathways

BackgroundPseudomonas aeruginosa (P. aeruginosa) is a common opportunistic pathogen responsible for skin infections. Tannins are recognized for their broad-spectrum antibacterial properties and their application in accelerating wound healing.ObjectiveThis study aimed to systematically delineate the concentration-dependent effects of tannic acid on P. aeruginosa, to decode its antibacterial mechanism by RNA-seq-driven transcriptomics, elucidate the underlying antibacterial mechanisms, and evaluate its therapeutic potential in promoting the healing of P. aeruginosa–infected wounds.ResultsHigh concentrations of tannic acid disrupted the integrity of the P. aeruginosa cell membrane, leading to the leakage of intracellular macromolecules, and inhibited bacterial growth by halting protein synthesis. At sub-inhibitory concentrations (sub-MICs), tannic acid significantly attenuated bacterial virulence by suppressing pyocyanin and rhamnolipid biosynthesis, biofilm formation, proteolytic activity, and bacterial motility. Transcriptomic profiling further indicated that tannic acid selectively regulated genes implicated in biofilm formation and efflux pump assembly. In a murine wound model infected with P. aeruginosa, tannic acid treatment significantly decreased bacterial burden, attenuated histopathological injury, contained infection progression, and expedited wound closure.ConclusionTannic acid exerts bacteriostatic action against P. aeruginosa and attenuates its pathogenicity by curbing virulence factor production and biofilm formation. Moreover, it significantly accelerates wound closure in P. aeruginosa infected wounds. These findings provide a theoretical basis for the development of tannic acid as a potential antimicrobial therapy.