Pathobiology 2027

Pandemics caused by microbial pathogens have caused countless human deaths and societal upheaval for millennia. Historically the molecular events contributing to pandemics were largely unknown. Biomedical scientists, historians, clerics and others were forced to infer causative factors or construct baroque and sometimes bizarre explanations to explain contributory pathogenesis events. Stimulated in part by the untimely death of the Muppeteer Jim Henson in 1990 caused by Streptococcus pyogenes (group A streptococcus, GAS) necrotizing pneumonia, we have applied the theory and techniques of molecular population genomics and microbial pathogenesis to address the fundamental problem of pandemics. Integrated analysis of very large populations of GAS obtained over decades from waves of human infections have yielded surprising basic science discoveries that have direct clinical and translational implications. Analogous approaches have more recently been used to investigate the COVID-19 pandemic and a rapid global increase in severe human infections caused by Streptococcus dysgalactiae subspecies equisimilis. These and other studies have taught that analysis of the molecular triggers contributing to microbial pandemics is a very exhilarating area of pathogenesis research that will provide new discoveries for centuries and stimulate subsequent generations of molecular pathogenesis students.