Strain-specific modulation of biofilm and motility in Pseudomonas aeruginosa by Danshen-derived compounds and their impact on antibiotic susceptibility

BackgroundMultidrug-resistant (MDR) Pseudomonas aeruginosa poses major therapeutic challenges due to biofilm-associated tolerance and limited antibiotic efficacy. Lipophilic diterpenoids from Salvia miltiorrhiza (Danshen) have reported antimicrobial potential, but their effects on P. aeruginosa biofilm phenotypes, motility, and antibiotic susceptibility remain poorly defined.Methods and resultsFive Danshen-derived compounds were tested for antibacterial activity, biofilm modulation, and motility inhibition in P. aeruginosa PAO1 and two MDR clinical isolates (designated XCH-MDR-01 and XCH-MDR-02). Antibacterial activity was negligible (MIC > 256 µmol L−1). Dihydrotanshinone I and tanshinone I enhanced PAO1 biofilm formation (20%–30%) but inhibited biofilm formation in MDR isolates (40%–50%) and disrupted established biofilms (50%–60% at 50 µmol L−1). Confocal microscopy confirmed reduced biofilm density and altered architecture in MDR isolates, contrasting with enhanced biofilms in PAO1. Motility was suppressed in MDR isolates but unaffected in PAO1. qPCR showed strain-specific regulation of wspR and pslA, with upregulation in PAO1 (2–3-fold) and downregulation (∼50%) in XCH-MDR-01. Co-treatment with dihydrotanshinone I or tanshinone I reduced ceftazidime MICs by 4–8-fold in MDR isolates.ConclusionsDanshen-derived diterpenoids exert strain-specific effects on P. aeruginosa biofilm formation and motility, and selectively potentiate ceftazidime activity against MDR isolates.