Genome-wide molecular dissection of serotype M3 group A Streptococcus strains causing two epidemics of invasive infections
Autor: | James M. Musser, Frank R. DeLeo, Donald E. Low, Adeline R. Whitney, Gail L. Sylva, Gerald J. Adams, Mengyao Liu, Stephen B. Beres, Stacy M. Ricklefs, Larye D. Parkins, Chanel Granville, Allison McGeer, Nancy P. Hoe, Daniel E. Sturdevant |
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Rok vydání: | 2004 |
Předmět: |
Serotype
Canada Genotype Streptococcus pyogenes Virulence Factors Population Virulence Biology Polymorphism Single Nucleotide Disease Outbreaks Bacterial Proteins Streptococcal Infections Genetic variation Gene duplication Humans education Genotyping Prophage Genetics Chromosome Aberrations education.field_of_study Antigens Bacterial Multidisciplinary Genetic Variation Genomics Biological Sciences Population Surveillance Carrier Proteins Sequence Analysis Genome Bacterial Bacterial Outer Membrane Proteins |
Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 101(32) |
ISSN: | 0027-8424 |
Popis: | Molecular factors that contribute to the emergence of new virulent bacterial subclones and epidemics are poorly understood. We hypothesized that analysis of a population-based strain sample of serotype M3 group A Streptococcus (GAS) recovered from patients with invasive infection by using genome-wide investigative methods would provide new insight into this fundamental infectious disease problem. Serotype M3 GAS strains ( n = 255) cultured from patients in Ontario, Canada, over 11 years and representing two distinct infection peaks were studied. Genetic diversity was indexed by pulsed-field gel electrophoresis, DNA–DNA microarray, whole-genome PCR scanning, prophage genotyping, targeted gene sequencing, and single-nucleotide polymorphism genotyping. All variation in gene content was attributable to acquisition or loss of prophages, a molecular process that generated unique combinations of proven or putative virulence genes. Distinct serotype M3 genotypes experienced rapid population expansion and caused infections that differed significantly in character and severity. Molecular genetic analysis, combined with immunologic studies, implicated a 4-aa duplication in the extreme N terminus of M protein as a factor contributing to an epidemic wave of serotype M3 invasive infections. This finding has implications for GAS vaccine research. Genome-wide analysis of population-based strain samples cultured from clinically well defined patients is crucial for understanding the molecular events underlying bacterial epidemics. |
Databáze: | OpenAIRE |
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