Streptococcus pyogenes can cause a variety of diseases in immunocompetent individuals, from pharyngotonsillitis to life-threatening invasive diseases like streptococcal toxic shock syndrome and rapidly progressing deep tissue infections, such as necrotizing fasciitis. Necrotizing fasciitis is often seen in combination with toxic shock, which further increases morbidity and mortality.
To gain insight into the pathogenesis of severe deep tissue infections, we have utilized a snap-frozen tissue biopsy material collected from patients with various soft tissue infections, including necrotizing fascitiis, myositis, and cellulitis caused by S. pyogenes. All patients had received intravenous clindamycin in combination with a β-lactam antibiotic at admission.
The studies revealed that severe soft tissue infections are characterized by massive bacterial load, presence of important streptococcal virulence factors including soluble M1-protein, the cysteine protease SpeB and superantigens, DNAses, and heavy infiltration of inflammatory cells and inflammatory mediators. Analyses of host-microbe interactions at the tissue site of infection have furthermore provided in vivo evidence for many of the immune evasion strategies previously described in vitro. Important bacterial resistance mechanisms at the tissue site include exploitation of human phagocytic cells as host cells thereby allowing persistence intracellularly, as well as protection against antimicrobial peptides by SpeB retained at the bacterial surface through GRAB-a2-macroglobulin complexes. It is clear that the pathogenesis of severe streptococcal tissue infections is multifactorial in nature. This complexity is important to consider in the design of novel therapeutic strategies, where IVIG represent one immunomodulatory therapy that should be evaluated further.