Staphylococcus aureus Toxins and Diabetic Foot Ulcers: Role in Pathogenesis and Interest in Diagnosis

Abstract

Infection of foot ulcers is a common, often severe and costly complication in diabetes. Diabetic foot infections (DFI) are mainly polymicrobial, and Staphylococcus aureus is the most frequent pathogen isolated. The numerous virulence factors and toxins produced by S. aureus during an infection are well characterized. However, some particular features could be observed in DFI. The aim of this review is to describe the role of S. aureus in DFI and the implication of its toxins in the establishment of the infection. Studies on this issue have helped to distinguish two S. aureus populations in DFI: toxinogenic S. aureus strains (harboring exfoliatin-, EDIN-, PVL- or TSST-encoding genes) and non-toxinogenic strains. Toxinogenic strains are often present in infections with a more severe grade and systemic impact, whereas non-toxinogenic strains seem to remain localized in deep structures and bone involving diabetic foot osteomyelitis. Testing the virulence profile of bacteria seems to be a promising way to predict the behavior of S. aureus in the chronic wounds.

Keywords: Staphylococcus aureus; diabetic foot infection; toxins.

Figure 1

Interactions between metabolic, anatomical and bacteriological factors in diabetic foot infection.

Figure 2

Worldwide geographic distribution of Gram-positive cocci (GP), S. aureus and Methicillin Resistant S. aureus (MRSA) isolated from diabetic foot ulcers. Red shading indicates regions where GP are predominant. Green shading indicates regions where Gram-negative bacilli are predominant.

Figure 3

Infection process and virulence factors of Staphylococcus aureus in diabetic foot infection; MSCRAMM: microbial surface components recognizing adhesive matrix molecules. S. aureus secretes several virulence factors that evade host immune defenses. α-hemolysin (or α-toxin), phenol-soluble modulins (PSMs) and Panton-Valentine leukocidin (PVL) have the capacity to lyse host cells, which is a mechanism to evade immune responses. In addition, S. aureus secretes factors that inhibit neutrophil function, such as chemotaxis inhibitory protein of staphylococci (CHIPS). In addition, S. aureus possesses factors that active lymphocyte T cells: the superantigens (SE: enterotoxins; SEI: enterotoxin-like protein; TSST: toxic shock-syndrome toxin). On the other side, exfoliative toxins (Ets) facilitate bacterial skin invasion.