Microbiome-guided prioritization of Corynebacterium striatum in diabetic foot ulcers and preclinical evaluation of tanshinone IIA.

BACKGROUND

Diabetic foot ulcers (DFUs) are characterized by impaired healing and infection, but microbial signatures linked to glycemic status and their therapeutic relevance remain unclear.

PURPOSE: To identify DFU taxa associated with glycemic status and test whether microbiome-guided prioritization can inform evaluation of Tanshinone IIA (Tan IIA).

STUDY

DESIGN

Clinical metagenomic discovery followed by in vitro functional and multi-omics analyses, biophysical studies, and in vivo evaluation.

METHODS

Wound samples from 54 DFU patients underwent HbA1c-stratified shotgun metagenomics. A prioritized patient-derived Corynebacterium striatum isolate was assessed for Tan IIA antibacterial and antibiofilm activity, multi-omics responses, and candidate-protein binding. Topical Tan IIA was tested in non-inoculated and C. striatum-inoculated diabetic wounds.

RESULTS

C. striatum was enriched in higher-HbA1c wounds and positively associated with continuous HbA1c (β = 0.422, 95% CI 0.095-0.748; P = 0.011; q = 0.064). Tan IIA inhibited the isolate (MIC = 64 μ g/ml), reduced biofilm biomass, and induced stress, redox, cell-envelope, and metabolic responses. SPR supported binding to MurD and TrxB. On day 14, wound closure was significantly greater in inoculated wounds (93.40% vs. 78.80%; adjusted P = 0.0187). In inoculated wounds, Tan IIA reduced EUB338-positive bacterial signal and viable counts versus vehicle (8.587 vs. 8.847 log10 CFU/g; adjusted P =  0.0480).

CONCLUSION

HbA1c-stratified metagenomics prioritized C. striatum as a glycemic-status-associated candidate. These findings support microbiome-guided preclinical evaluation of plant-derived Tan IIA as a topical candidate for infected DFUs.