Abstract
ABSTRACTFor over a century, a fundamental objective in infection biology research has been to understand the molecular processes contributing to the origin and perpetuation of epidemics. Divergent hypotheses have emerged concerning the extent to which environmental events or pathogen evolution dominates in these processes. Remarkably few studies bear on this important issue. Based on population pathogenomic analysis of 1,200 Streptococcus pyogenes type emm89 infection isolates, we report that a series of horizontal gene transfer events produced a new pathogenic genotype with increased ability to cause infection, leading to an epidemic wave of disease on at least two continents. In the aggregate, these and other genetic changes substantially remodeled the transcriptomes of the evolved progeny, causing extensive differential expression of virulence genes and altered pathogen-host interaction, including enhanced immune evasion. Our findings delineate the precise molecular genetic changes that occurred and enhance our understanding of the evolutionary processes that contribute to the emergence and persistence of epidemically successful pathogen clones. The data have significant implications for understanding bacterial epidemics and for translational research efforts to blunt their detrimental effects.
Highlights
For over a century, a fundamental objective in infection biology research has been to understand the molecular processes contributing to the origin and perpetuation of epidemics
Considerable effort has been expended in the last 40 years to understand the genetic diversity and population structure of many bacterial pathogens, especially those that detrimentally affect human and livestock health and cause epidemics [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27]. These studies have led to the general concept that some bacterial species are clonal, with relatively little evidence that horizontal gene transfer (HGT) and recombination shape species diversity, whereas other bacterial pathogens are highly recombinogenic, with species diversity mediated by extensive HGT events [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27]
These factors afford considerable advantages in the use of S. pyogenes as a model system compared to many other pathogenic bacteria such as E. coli, S. enterica, and S. aureus
Summary
A fundamental objective in infection biology research has been to understand the molecular processes contributing to the origin and perpetuation of epidemics. Additional evidence supporting the notion of upregulation of SPN and SLO as a contributing cause of S. pyogenes epidemic disease was found by sequence analysis of 1,125 emm genomes [35] obtained in comprehensive population-based surveillance studies conducted in the United States, Finland, and Iceland between 1995 and 2013 Among these emm strains, we identified three distinct phylogenetic clades (designated clade 1, clade 2, and clade 3). Progress is being made in understanding genomic alterations that are linked with increases in disease frequency and severity in some human pathogens Despite these advances, very little analogous work has been conducted to investigate global changes in gene expression that may contribute to the origin and perpetuation of bacterial epidemics. The overall strategy used as described here is of general utility and pertinence to the investigation of other pathogens
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