FIGURE 2.

Model of mechanisms contributing to antibiotic failure during Group A Streptococcus (GAS) infections. Community-mediated resistance mediated by protection by endogenous microbiota is likely most prevalent during pharyngitis and not invasive infections, where GAS most often exists as a monoculture. Persisters, resistant through altered growth rates or other epigenetic states, can contribute to treatment failure of any infection. The formation of biofilms, invasion of epithelial cells, and survival within phagocytes can similarly occur during any infection and serve to shield single bacterium from antibiotic action. During invasive infections in particular, inflammation- and toxin-mediated necrosis of tissue and thrombosis of dermal vasculature can limit antibiotic perfusion, necessitating surgical removal of the infected tissue.