ArticleProceedings of the National Academy of Sciences of the United States of America2010
Molecular complexity of successive bacterial epidemics deconvoluted by comparative pathogenomics.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers.
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Who cites it
107 citing papers in PubMed, 167 citations in OpenAlex.
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- Manganese uptake by MtsABC contributes to the pathogenesis of human pathogen group A streptococcus by resisting host nutritional immune defenses.Infection and immunity · 2024Article
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- The Lost and Found: Unraveling the Functions of Orphan Genes.Journal of developmental biology · 2023Review
- A Novel CovS Variant Harbored by a Colonization Strain Reduces Streptococcus pyogenes Virulence.Journal of bacteriology · 2023Article
- Annotated Whole-Genome Multilocus Sequence Typing Schema for Scalable High-Resolution Typing of Streptococcus pyogenes.Journal of clinical microbiology · 2022Article
- Genomic Characterization of Group A Streptococci Causing Pharyngitis and Invasive Disease in Colorado, USA, June 2016- April 2017.The Journal of infectious diseases · 2022Article
- CovS inactivation reduces CovR promoter binding at diverse virulence factor encoding genes in group A Streptococcus.PLoS pathogens · 2022Article
- Characterization of the Type I Restriction Modification System Broadly Conserved among Group A Streptococci.mSphere · 2021Article
- The LiaFSR Transcriptome Reveals an Interconnected Regulatory Network in Group A Streptococcus.Infection and immunity · 2021Article
- Population Genomics ofmSystems · 2021Article
- Colonization of the Murine Oropharynx by Streptococcus pyogenes Is Governed by the Rgg2/3 Quorum Sensing System.Infection and immunity · 2020Article
47 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 8 institutions in 2 countries.
Funding
Abstract
Understanding the fine-structure molecular architecture of bacterial epidemics has been a long-sought goal of infectious disease research. We used short-read-length DNA sequencing coupled with mass spectroscopy analysis of SNPs to study the molecular pathogenomics of three successive epidemics of invasive infections involving 344 serotype M3 group A Streptococcus in Ontario, Canada. Sequencing the genome of 95 strains from the three epidemics, coupled with analysis of 280 biallelic SNPs in all 344 strains, revealed an unexpectedly complex population structure composed of a dynamic mixture of distinct clonally related complexes. We discovered that each epidemic is dominated by micro- and macrobursts of multiple emergent clones, some with distinct strain genotype-patient phenotype relationships. On average, strains were differentiated from one another by only 49 SNPs and 11 insertion-deletion events (indels) in the core genome. Ten percent of SNPs are strain specific; that is, each strain has a unique genome sequence. We identified nonrandom temporal-spatial patterns of strain distribution within and between the epidemic peaks. The extensive full-genome data permitted us to identify genes with significantly increased rates of nonsynonymous (amino acid-altering) nucleotide polymorphisms, thereby providing clues about selective forces operative in the host. Comparative expression microarray analysis revealed that closely related strains differentiated by seemingly modest genetic changes can have significantly divergent transcriptomes. We conclude that enhanced understanding of bacterial epidemics requires a deep-sequencing, geographically centric, comparative pathogenomics strategy.
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