A half-century of streptococcal research: then & now.

Research on Group A streptococci (GAS) before 1950 paved the way for successful clinical trials to prevent acute rheumatic fever (ARF) by treating the prior streptococcal infection with penicillin. Prevention of ARF has led to almost complete disappearance of rheumatic heart disease in the industrialized world, but has yet to be accomplished in developing countries, where most of the world's populations reside. Twenty years of research beginning in 1918 by Lancefield and others delineated the modern classification of haemolytic streptococci and led to the recognition that only Group A is responsible for the pharyngitis that causes ARF. M-protein, identified as a major virulence factor, is a powerful inhibitor of phagocytosis, and antibodies to it promote type-specific phagocytosis and therefore type-specific immunity. Other virulent properties of GAS include a bulky capsule, as well as extracellular toxins such as streptolysins S and O and streptococcal proteinase. McCarty and others pursued the cell biology of GAS and identified the cellular localization of various antigenic components. The discovery of purified M-protein as a helical coiled-coiled fibrillar protein has sparked development of M-protein vaccine. US, UK, and Trinidad scientists described differences between streptococcal infections of the throat and skin and noted particularly that many of the GAS M-types that cause impetigo are less likely to cause pharyngitis. GAS impetigo may cause acute glomerulonephritis, but such infections do not result in ARF. The changing manifestations of disease over time and the evolution of microbes are common themes in medicine today. These themes are relevant to GAS pharyngitis and ARF, especially the decline in the incidence of severe ARF and the decrease in severity of GAS pharyngitis. Research on GAS bacteriophages led to the discovery of a relationship between lysogenic GAS and production of erythrogenic toxin and has broadened approaches to the molecular epidemiology of GAS virulence. The 21st century begins with determination of the complete genome sequence of M-1, M-18, and M-3 strains of GAS. These studies provide evidence for phage-encoded toxins, high-virulence phenotypes, and clone emergence. This research will reveal genetic processes at the molecular level that control the emergence and decline of streptococcal diseases in different places and times and the shifting patterns in clinical manifestations.