Dataset Information

Genomics and Proteomics Provide New Insight into the Commensal and Pathogenic Lifestyles of Bovine and Human-associated Staphylococcus epidermidis

ABSTRACT: The goal of the present study is to understand mechanisms by which SE can infect the bovine host and persist in the mammary gland. For this purpose we determined the whole genome and four plasmid sequences of the SE strain PM221 originating from spontaneous persistent bovine IMI. We compared the genomic data with those of ATCC12228 and RP62A to screen for conserved and acquired gene pools. To confirm and complement these findings two-dimensional difference gel electrophoresis (2D DIGE) involving each three strains, surfome shaving and experimental infections in a bovine model was applied to indicate potential differences.

OTHER RELATED OMICS DATASETS IN: PRJEB5186

INSTRUMENT(S): QSTAR

ORGANISM(S): Staphylococcus Epidermidis

SUBMITTER: Pia SiljamÃ¤ki

LAB HEAD: Tuula A Nyman

PROVIDER: PXD000683 | Pride | 2014-07-15

REPOSITORIES: Pride

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Publications

Genomics and Proteomics Provide New Insight into the Commensal and Pathogenic Lifestyles of Bovine- and Human-Associated Staphylococcus epidermidis Strains.

Savijoki Kirsi K Iivanainen Antti A Siljamäki Pia P Laine Pia K PK Paulin Lars L Karonen Taru T Pyörälä Satu S Kankainen Matti M Nyman Tuula A TA Salomäki Tiina T Koskinen Patrik P Holm Liisa L Simojoki Heli H Taponen Suvi S Sukura Antti A Kalkkinen Nisse N Auvinen Petri P Varmanen Pekka P

Journal of proteome research 20140718 8

The present study reports comparative genomics and proteomics of Staphylococcus epidermidis (SE) strains isolated from bovine intramammary infection (PM221) and human hosts (ATCC12228 and RP62A). Genome-level profiling and protein expression analyses revealed that the bovine strain and the mildly infectious ATCC12228 strain are highly similar. Their genomes share high sequence identity and synteny, and both were predicted to encode the commensal-associated fdr marker gene. In contrast, PM221 was ...[more]

PMID: 25014494

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Project description:Drug-tolerant “persister” tumor cells underlie the emergence of drug-resistant clones contribute to relapse and disease progression; thus, identifying actionable targets that disable persisters and mitigate relapse are a high priority need. Although the BCL2-targeting agent venetoclax (ABT-199) has shown promising responses in mantle cell and double hit B cell lymphomas, resistance often arises, yet mechanistically how this occurs is unclear. Here we report that ABT-199 resistance can evolve from persister clones that have selective deletions at 18q21 that involve the drug target BCL2 and the apoptotic regulators Noxa (PMAIP1) and TCF4. Notably, reprogramming of super enhancers (SE) in persisters contributes to resistance, where there is a selection for SE-directed overexpression of the apoptotic regulator BCL2A1 and oncogenic transcription factors IKZF1 and FOXC1. At the same time, the SE reprogramming confers an opportunity for overcoming ABT-199 resistance. An unbiased drug screen on a platform that recapitulates the lymphoma microenvironment revealed that persisters are vulnerable to inhibitors of transcription initiation and elongation, and especially so to inhibitors of cyclin-dependent kinase 7 (CDK7) that is essential for transcription initiation. Specifically, CDK7 loss or inhibition eliminated the persister phenotype by disabling SE-driven expression of BCL2A1, IKZF1 and FOXC1. Thus, the co-treatment of ABT-199 with CDK7 inhibitors blocked the evolution of drug resistance, and provoked tumor regression in models of mantle cell lymphoma (MCL) and double hit lymphomas (DHL) that overexpress both MYC and BCL2. Together, these findings establish loss of apoptotic regulators and an adaptive transcriptional response as drug resistance mechanisms in lymphoma, more importantly, establish a rationale for transcription inhibition-based combination strategies to prevent and overcome drug resistance in B cell malignancies toward BCL2 inhibitor.

Dataset Information

Genomics and Proteomics Provide New Insight into the Commensal and Pathogenic Lifestyles of Bovine and Human-associated Staphylococcus epidermidis

Publications

Genomics and Proteomics Provide New Insight into the Commensal and Pathogenic Lifestyles of Bovine- and Human-Associated Staphylococcus epidermidis Strains.

Similar Datasets

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