Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Whole genome transcritptional comparison of Group A Streptococcus (Streptococcus pyogenes) serotype M1 pre-epidemic and epidemic isolates

ABSTRACT: This transcriptional analysis is a follow up to a population genomic investigation of 3615 Streptococcus pyogenes serotype M1 strains whch are responsible for an epidemic of human invasive infections (www.pnas.org/cgi/doi/10.1073/pnas.1403138111), The goal was to assess gene expression differences between predecessor pre-epidemic M1 strains and their descendent epidemic M1 strains to gain insights into the underlying genetic basis for the shift in the frequency and severity of human infections caused by these pathogenic bacteria The transcriptomes of 7 GAS M1 strains, 4 pre-epidemic and 3 epidemic, were compared at two phases of growth, mid-exponential and early-stationary, using 3 biologial replicates, to identify genes differentially expressed between the pre-epidemic and epidemic isolates with the goal of to gaining insight into the underlying genetic basis for the evolutionary emergence, increased frequency and severity of the epidemic strains relative to the pre-epidemic strains

ORGANISM(S): Streptococcus pyogenes

SUBMITTER: Stephen Beres

PROVIDER: E-GEOD-70496 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Listeria monocytogenes is a gram-positive, food-borne pathogen responsible for invasive infections with high overall mortality. Early host defenses encountered by L. monocytogenes following ingestion include low pH of the stomach and bile present in the small intestinal lumen. We hypothesized that “epidemic” strains are better able to withstand exposure to low pH and bile encountered in the gastrointestinal tract as compared to most “environmental” strains. Furthermore, we hypothesized that epidemic and environmental strains would have distinct transcriptional programs upon exposure to these conditions. Our treatments included 1 hr exposure to acid (pH 5.5 and 3.5) and bile (0.3%) stress. Strains were pre-exposed to pH 5.5 (1 hr) before being treated with pH 3.5. We used a collection of 12 previously characterized epidemic and environmental strains and each strainXtreatment combination included 3 biological replicates for each microarray experiment. All microarray experiments were two color competitive hybridizations that paired experimental conditions with the same strain at neutral pH for acid stress and pH 5.5 for bile stress. Transcriptomes of environmental strains exposed to acid and bile stress showed remarkably greater number of genes with differences of ≥2-fold expression levels as compared to epidemic strains (5 and 7, respectively). Environmental strains were characterized by up-regulation of several stress related genes and down-regulation of several cell envelope biosynthesis and virulence related genes, suggesting that complex regulatory networks orchestrate the cellular changes in the environmental strains to overcome stressful environments. The transcriptome of epidemic strains, in contrast, showed muted responses to these stress conditions implying their pre-adaptability to acid and bile stress encountered during natural infection that may enable epidemic strains to survive and become “primed” for subsequent colonization and infection in the lower gastrointestinal tract. Keywords: stress response, comparative transcriptomics, acid-adaptation, differential virulence, acid-stress response, bile-stress response

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Whole genome transcritptional comparison of Group A Streptococcus (Streptococcus pyogenes) serotype M1 pre-epidemic and epidemic isolates

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