Dataset Information

Proteome-wide selected reaction monitoring assays for the human pathogen Streptococcus pyogenes.

ABSTRACT: Selected reaction monitoring mass spectrometry (SRM-MS) is a targeted proteomics technology used to identify and quantify proteins with high sensitivity, specificity and high reproducibility. Execution of SRM-MS relies on protein-specific SRM assays, a set of experimental parameters that requires considerable effort to develop. Here we present a proteome-wide SRM assay repository for the gram-positive human pathogen group A Streptococcus. Using a multi-layered approach we generated SRM assays for 10,412 distinct group A Streptococcus peptides followed by extensive testing of the selected reaction monitoring assays in >200 different group A Streptococcus protein pools. Based on the number of SRM assay observations we created a rule-based selected reaction monitoring assay-scoring model to select the most suitable assays per protein for a given cellular compartment and bacterial state. The resource described here represents an important tool for deciphering the group A Streptococcus proteome using selected reaction monitoring and we anticipate that concepts described here can be extended to other pathogens.

SUBMITTER: Karlsson C

PROVIDER: S-EPMC3535367 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Proteome-wide selected reaction monitoring assays for the human pathogen Streptococcus pyogenes.

Karlsson Christofer C Malmström Lars L Aebersold Ruedi R Malmström Johan J

Nature communications 20120101

Selected reaction monitoring mass spectrometry (SRM-MS) is a targeted proteomics technology used to identify and quantify proteins with high sensitivity, specificity and high reproducibility. Execution of SRM-MS relies on protein-specific SRM assays, a set of experimental parameters that requires considerable effort to develop. Here we present a proteome-wide SRM assay repository for the gram-positive human pathogen group A Streptococcus. Using a multi-layered approach we generated SRM assays fo ...[more]

PMID: 23250431

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Project description:UNLABELLED: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. 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. IMPORTANCE:The confluence of studies of molecular events underlying pathogen strain emergence, evolutionary genetic processes mediating altered virulence, and epidemics is in its infancy. Although understanding these events is necessary to develop new or improved strategies to protect health, surprisingly few studies have addressed this issue, in particular, at the comprehensive population genomic level. Herein we establish that substantial remodeling of the transcriptome of the human-specific pathogen Streptococcus pyogenes by horizontal gene flow and other evolutionary genetic changes is a central factor in precipitating and perpetuating epidemic disease. The data unambiguously show that the key outcome of these molecular events is evolution of a new, more virulent pathogenic genotype. Our findings provide new understanding of epidemic disease.

Dataset Information

Proteome-wide selected reaction monitoring assays for the human pathogen Streptococcus pyogenes.

Publications

Proteome-wide selected reaction monitoring assays for the human pathogen Streptococcus pyogenes.

Similar Datasets

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