Molecular analysis of serotype M28 group A Streptococcus.

摘要

The manifestation of Group A Streptococcus (GAS) disease includes pharyngitis, pyoderma, severe invasive episodes, and post-streptococcal sequelae such as acute glomeruloneprhitis and acute rheumatic fever. The re-emergence of GAS as a pathogenic agent responsible for major human morbidity and mortality has stimulated renewed interest in the molecular basis of virulence for this organism. An improved understanding of the genetic factors underlying changes in GAS epidemic behavior has been possible through the combined use of epidemiological surveillance data and modern molecular biology techniques. Recent completion of 12 GAS genome sequences has yielded extensive new information important for pathogenesis research and provided new insight into the extent of strain variation within and between serotypes. Importantly, these studies have revealed that bacteriophages and other horizontally transferred genetic elements are the primary source of variation in gene content between strains. These genetic differences may be partly responsible for differences in disease outcome.;The work presented here describes studies of serotype M28 GAS designed to identify factors which may be responsible for the enrichment of this serotype in puerperal sepsis and other types of infections. The strategy applied in this study includes comparative genomics to identify novel GAS extracellular proteins and comprehensive population genetic analyses to describe the distribution of proven and putative extracellular virulence factors in natural populations of GAS. Knowledge of the temporal and geographic distribution of virulence genes may help to explain particular disease outbreaks and fluctuations in disease frequency and severity, and provide molecular insights on specific disease associations. Subsequent molecular analyses were performed to determine antigenicity of these molecules and to provide a preliminary understanding of biological function.;The results of these combined studies provide the foundation for in-depth characterization of several secreted and surface proteins identified in GAS strains associated with puerperal infections. The integrated investigative strategies employed in this study will complement classical methods of determining mechanisms of bacterial pathogenesis and thereby significantly enhance our understanding of host-pathogen interactions.