<i>Staphylococcus argenteus</i> ST2250 from diabetic foot sepsis: genomic insights into resistance and virulence

<h4>Background</h4><i>Staphylococcus argenteus</i> ST2250 is a globally disseminated clone, but clinical data on its life-threatening infections in high-risk populations and molecular dissemination evidence remain limited.<h4>Methods</h4>We integrated clinical data, antimicrobial susceptibility testing, and whole-genome sequencing (WGS) for four <i>S. argenteus</i> isolates-including paired blood and wound isolates from a septic shock case-comparatively analyzed against 370 global genomes. Clonal relatedness was assessed by core-genome SNP analysis, with resistance and virulence genes.<h4>Results</h4>A 53-year-old uncontrolled type 2 diabetes patient developed septic shock with pronounced inflammatory response (PCT 13.32 ng/mL, CRP 364.85 mg/L). WGS confirmed 0 core-genome SNP differences between blood (20250131) and wound (20250137) isolates, validating clonal transmission from the foot ulcer. All four institutional isolates were ST2250, sharing 12 core antimicrobial resistance-associated (AMR) genes. Global analysis identified the dominance of ST2250 (55.9% of 370 genomes), with 101 out of 147 (68.7%) observed between 2015 and 2019 among the dated genomes (68.7% of 268 genomes with a known collection year). ST2250 exhibited unique AMR signatures: highest <i>blaZ</i> prevalence (66.7%), near-universal <i>fosB</i> (98.5%), and unique <i>tet(L)</i> (42.5%) and <i>APH(3')-IIIa</i> (48.8%) carriage absent in ST2198, ST2793, ST2854, and ST5961. Virulence profiling revealed ST2250-specific features: significantly reduced clfB (11.1% vs. 87.5-100% in other STs, P<0.01), complete absence of <i>set23</i> and ESAT-6 system components (0% vs. 100%), and near-universal conservation of <i>cap8</i> operon (98.6%), <i>lukF-PV</i> (98.6%), and set25/26 (98.6%).<h4>Conclusions</h4>This study provides genetic validation of <i>S. argenteus</i> ST2250-induced septic shock originating from diabetic foot infection. The clone's global dominance, distinctive resistance profile, and reconfigured virulence architecture highlight the urgent need for enhanced diagnostic stewardship, targeted surveillance in diabetic populations, and rational antimicrobial use.