Virulence factors and clonal diversity of Staphylococcus aureus in colonization and wound infection with emphasis on diabetic foot infection

Abstract

Foot ulcer is a common complication in diabetic subjects and infection of these wounds contributes to increased rates of morbidity and mortality. Diabetic foot infections are caused by a multitude of microbes and Staphylococcus aureus, a major nosocomial and community-associated pathogen, significantly contributes to wound infections as well. Staphylococcus aureus is also the primary pathogen commonly associated with diabetic foot osteomyelitis and can cause chronic and recurrent bone infections. The virulence capability of the pathogen and host immune factors can determine the occurrence and progression of S. aureus infection. Pathogen-related factors include complexity of bacterial structure and functional characteristics that provide metabolic and adhesive properties to overcome host immune response. Even though, virulence markers and toxins of S. aureus are broadly similar in different wound models, certain distinguishing features can be observed in diabetic foot infection. Specific clonal lineages and virulence factors such as TSST-1, leukocidins, enterotoxins, and exfoliatins play a significant role in determining wound outcomes. In this review, we describe the role of specific virulence determinants and clonal lineages of S. aureus that influence wound colonization and infection with special reference to diabetic foot infections.

Keywords: Clonal diversity; Diabetic foot; Infection; Osteomyelitis; Staphylococcus aureus; Toxins; Virulence.

Fig. 1

Schematic diagram illustrating major S. aureus factors associated with DFI and DFOM. (Adapted from Kong et al. [13]). ACME, arginine catabolic mobile element; agr, accessory gene regulator; Bbp, bone sialoprotein-binding protein; CC, clonal complexes; Cna, collagen adhesin; FnBP, fibronectin-binding protein; MSCRAMMs, microbial surface components recognizing adhesive matrix molecules; PMT complex, PSM transporter complex; PSM, phenol-soluble modulins; PVL, Panton-Valentine leukocidin; SAgs, super antigens; sarA, staphylococcal accessory regulator; sae, response regulator; SdrD, serine–aspartate repeat-containing protein D; SEs, staphylococcal enterotoxins; SspA, staphylococcal serine protease; SspB, cysteine protease; TSST-1, toxic shock syndrome toxin-1