Clinical and molecular epidemiology of type 2 diabetes mellitus-associated intestinal Staphylococcus aureus colonization

ABSTRACT Intestinal Staphylococcus aureus colonization in type 2 diabetes mellitus (T2DM) remains poorly defined with respect to prevalence, clinical associations, and molecular characteristics. We investigated intestinal S. aureus colonization in 142 patients with T2DM and characterized the recovered isolates using antimicrobial susceptibility testing, resistance gene profiling, multilocus sequence typing, accessory gene regulator typing, spa typing, and whole-genome sequencing. Clinical and laboratory characteristics were compared between colonized and non-colonized patients, and siderophore production and biofilm formation were evaluated in major molecular types. S. aureus colonization was identified in 30 patients (21.1%, 95% confidence interval: 15.2%–28.6%) based on a single fecal sample per patient, including one methicillin-resistant isolate. Isolates remained highly susceptible to most tested antimicrobials, except penicillin. The β-lactamase gene blaZ was the most prevalent resistance determinant (83.3%). MLST revealed a polyclonal population dominated by ST15 (30.0%), ST1156 (26.7%), and ST5 (26.7%), with agr II (56.7%) and spa type t84 (43.3%) being the most common types. Whole-genome sequencing further demonstrated distinct plasmid architectures between methicillin-susceptible S. aureus and methicillin-resistant S. aureus (MRSA) isolates and identified an SCCmec IVc (2B) element in the MRSA isolate. Siderophore production was significantly higher in ST15 and ST1156 than in ST5, whereas biofilm formation did not. These findings provide a comprehensive characterization of the clinical and epidemiological profiles of intestinal S. aureus colonization in patients with T2DM and highlight the need for continued genomic surveillance and mechanistic studies to support infection prevention and therapeutic strategies. IMPORTANCE Intestinal Staphylococcus aureus colonization in type 2 diabetes mellitus (T2DM) has remained largely uncharacterized despite the well-documented heightened infection risk in this population. Here, we show that 21.1% (95% confidence interval: 15.2%–28.6%) of hospitalized T2DM patients harbor gut S. aureus (only 3.3% methicillin-resistant S. aureus [MRSA]). The isolates form a polyclonal population dominated by ST15, ST1156, and ST5, carry predominantly blaZ , and display lineage-specific differences in siderophore production—an iron-acquisition trait critical for gut persistence. These data establish the diabetic intestine as a clinically relevant reservoir, underscore the limitations of nares-only surveillance, and highlight the need for integrated genomic and mechanistic studies to guide infection prevention in T2DM.