Virulence potential of Staphylococcus aureus strains isolated from diabetic foot ulcers: a new paradigm

Abstract

Objective: To assess the virulence potential of Staphylococcus aureus isolated from diabetic foot ulcers and to discriminate non-infected from infected ulcers.

Research design and methods: Diabetic patients hospitalized in a diabetic foot department f with a foot ulcer were prospectively enrolled if they had been free of antibiotics treatment over the previous 6-months . At admission, ulcers were classified as infected or non-infected based on clinical examination, according to the IWGDF system. Only patients carrying S. aureus as the sole pathogen were included. In individuals with a grade 1 ulcer, a second bacterial specimen was obtained one month later. Using virulence genotyping markers, clonality tools and an in vivo Caenorhabditis elegans model, we correlated the virulence of 132 S. aureus strains with grade, time of collection and ulcer outcome.

Results: Among virulence genes, the most relevant combination derived from the logistic regression was the association of cap8, sea, sei, lukE and hlgv (AUC 0.958). These markers were useful to distinguish non-infected (grade 1)/infected (grades 2-4) ulcers and to predict wound status at the follow-up. Using the nematode model, S. aureus strains isolated from grade 1 ulcers were found to be significantly less virulent than strains from grade ≥2 ulcers (P<0.001).

Conclusions: This study highlighted the coexistence of two S. aureus populations on diabetic foot ulcers. A combination of 5 genes was discovered that may help distinguish colonized grade 1 from infected grade ≥2 wounds, predict ulcer outcome and contribute to a more appropriate use of antibiotics.