Streptococcal molecular mimicry: Pathogenesis, autoimmunity, and vaccines

Group A Streptococcus (GAS) and Group B Streptococcus (GBS) are two of the most important human leading human bacterial pathogens. GAS is the cause of “strep throat”, with 700 million cases per year globally, but also has the potential to produce severe invasive diseases including necrotizing fasciitis (“flesh-eating disease”) and toxic shock syndrome, even in previously healthy individuals. GBS colonizes the lower GI tract and vaginal epithelium in healthy women, but can cause severe infections including sepsis and meningitis in newborn infants.  Both bacteria have capsules composed of sugar molecules that resemble sugars naturally present in humans.  This “wolf in sheep’s clothing disguise” allows the pathogen to hide from the immune system or down-regulate immune cell activity, thereby contributing to their disease potential.  GAS also has another sugar molecule in its cell wall that might contribute to cross-reactive immunity involved in the later development of rheumatic heart disease, a major cause of morbidity and mortality in the developing world.  This complicates the prospect of vaccine development, but our genetic discoveries may have identified a workaround.