2019The Journal of UrologyRequires access

MP71-01 GENETICALLY DIVERSE UROPATHOGENIC ESCHERICHIA COLI ADOPT A COMMON TRANSCRIPTIONAL PROGRAM IN PATIENTS WITH URINARY TRACT INFECTIONS

Anna Sintsova, Ali Pirani, Sargurunathan Subashchandrabose, Evan S. Snitkin, Harry L. T. Mobley

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Abstract

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder I (MP71)1 Apr 2019MP71-01 GENETICALLY DIVERSE UROPATHOGENIC ESCHERICHIA COLI ADOPT A COMMON TRANSCRIPTIONAL PROGRAM IN PATIENTS WITH URINARY TRACT INFECTIONS Anna Sintsova*, Ali Pirani, Sargurunathan Subashchandrabose, Evan Snitkin, and Harry L.T. Mobley Anna Sintsova*Anna Sintsova* More articles by this author , Ali PiraniAli Pirani More articles by this author , Sargurunathan SubashchandraboseSargurunathan Subashchandrabose More articles by this author , Evan SnitkinEvan Snitkin More articles by this author , and Harry L.T. MobleyHarry L.T. Mobley More articles by this author View All Author Informationhttps://doi.org/10.1097/01.JU.0000557113.84726.1dAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVES: Uropathogenic Escherichia coli (UPEC) is the major causative agent of uncomplicated urinary tract infections (UTIs). UPEC strains carry diverse assortments of virulence factors and a common virulence genotype responsible for urinary tract infection is yet to be defined. We hypothesized that studying patterns of gene expression in patients might identify universal bacterial features that enable uropathogenesis. METHODS: Using RNA sequencing technology, we examined UPEC gene expression directly in 14 patients presenting with uncomplicated UTI and compared it to the gene expression of identical strains cultured in vitro to mid-exponential stage in filter-sterilized human urine. RESULTS: Here we identify a common transcriptional program shared by genetically diverse UPEC strains isolated from 14 patients with uncomplicated UTIs. Strikingly, the conserved gene expression program in patients is distinct from one observed during in vitro urine culture of the identical strains. Moreover, regulatory network analysis reveals that drastic downregulation of key metabolic regulons in all 14 UPEC strains facilitates markedly increased expression of translation and replication machinery. CONCLUSIONS: Taken together, our study identifies for the first time a common thread underlying UTI and illuminates the molecular underpinnings that likely facilitate the remarkably fast growth rate of UPEC that has been previously observed in infected patients. Source of Funding: AUA Fellowship, NIH award number R01 DK094777 Ann Arbor, MI; Winston-Salem, NC; Ann Arbor, MI© 2019 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 201Issue Supplement 4April 2019Page: e1046-e1046 Advertisement Copyright & Permissions© 2019 by American Urological Association Education and Research, Inc.MetricsAuthor Information Anna Sintsova* More articles by this author Ali Pirani More articles by this author Sargurunathan Subashchandrabose More articles by this author Evan Snitkin More articles by this author Harry L.T. Mobley More articles by this author Expand All Advertisement PDF downloadLoading ...

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You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder I (MP71)1 Apr 2019MP71-01 GENETICALLY DIVERSE UROPATHOGENIC ESCHERICHIA COLI ADOPT A COMMON TRANSCRIPTIONAL PROGRAM IN PATIENTS WITH URINARY TRACT INFECTIONS Anna Sintsova*, Ali Pirani, Sargurunathan Subashchandrabose, Evan Snitkin, and Harry L.T. Mobley Anna Sintsova*Anna Sintsova* More articles by this author , Ali PiraniAli Pirani More articles by this author , Sargurunathan SubashchandraboseSargurunathan Subashchandrabose More articles by this author , Evan SnitkinEvan Snitkin More articles by this author , and Harry L.T. MobleyHarry L.T. Mobley More articles by this author View All Author Informationhttps://doi.org/10.1097/01.JU.0000557113.84726.1dAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVES: Uropathogenic Escherichia coli (UPEC) is the major causative agent of uncomplicated urinary tract infections (UTIs). UPEC strains carry diverse assortments of virulence factors and a common virulence genotype responsible for urinary tract infection is yet to be defined. We hypothesized that studying patterns of gene expression in patients might identify universal bacterial features that enable uropathogenesis. METHODS: Using RNA sequencing technology, we examined UPEC gene expression directly in 14 patients presenting with uncomplicated UTI and compared it to the gene expression of identical strains cultured in vitro to mid-exponential stage in filter-sterilized human urine. RESULTS: Here we identify a common transcriptional program shared by genetically diverse UPEC strains isolated from 14 patients with uncomplicated UTIs. Strikingly, the conserved gene expression program in patients is distinct from one observed during in vitro urine culture of the identical strains. Moreover, regulatory network analysis reveals that drastic downregulation of key metabolic regulons in all 14 UPEC strains facilitates markedly increased expression of translation and replication machinery. CONCLUSIONS: Taken together, our study identifies for the first time a common thread underlying UTI and illuminates the molecular underpinnings that likely facilitate the remarkably fast growth rate of UPEC that has been previously observed in infected patients. Source of Funding: AUA Fellowship, NIH award number R01 DK094777 Ann Arbor, MI; Winston-Salem, NC; Ann Arbor, MI© 2019 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 201Issue Supplement 4April 2019Page: e1046-e1046 Advertisement Copyright & Permissions© 2019 by American Urological Association Education and Research, Inc.MetricsAuthor Information Anna Sintsova* More articles by this author Ali Pirani More articles by this author Sargurunathan Subashchandrabose More articles by this author Evan Snitkin More articles by this author Harry L.T. Mobley More articles by this author Expand All Advertisement PDF downloadLoading ...

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You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder I (MP71)1 Apr 2019MP71-01 GENETICALLY DIVERSE UROPATHOGENIC ESCHERICHIA COLI ADOPT A COMMON TRANSCRIPTIONAL PROGRAM IN PATIENTS WITH URINARY TRACT INFECTIONS Anna Sintsova*, Ali Pirani, Sargurunathan Subashchandrabose, Evan Snitkin, and Harry L.T. Mobley Anna Sintsova*Anna Sintsova* More articles by this author , Ali PiraniAli Pirani More articles by this author , Sargurunathan SubashchandraboseSargurunathan Subashchandrabose More articles by this author , Evan SnitkinEvan Snitkin More articles by this author , and Harry L.T. MobleyHarry L.T. Mobley More articles by this author View All Author Informationhttps://doi.org/10.1097/01.JU.0000557113.84726.1dAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVES: Uropathogenic Escherichia coli (UPEC) is the major causative agent of uncomplicated urinary tract infections (UTIs). UPEC strains carry diverse assortments of virulence factors and a common virulence genotype responsible for urinary tract infection is yet to be defined. We hypothesized that studying patterns of gene expression in patients might identify universal bacterial features that enable uropathogenesis. METHODS: Using RNA sequencing technology, we examined UPEC gene expression directly in 14 patients presenting with uncomplicated UTI and compared it to the gene expression of identical strains cultured in vitro to mid-exponential stage in filter-sterilized human urine. RESULTS: Here we identify a common transcriptional program shared by genetically diverse UPEC strains isolated from 14 patients with uncomplicated UTIs. Strikingly, the conserved gene expression program in patients is distinct from one observed during in vitro urine culture of the identical strains. Moreover, regulatory network analysis reveals that drastic downregulation of key metabolic regulons in all 14 UPEC strains facilitates markedly increased expression of translation and replication machinery. CONCLUSIONS: Taken together, our study identifies for the first time a common thread underlying UTI and illuminates the molecular underpinnings that likely facilitate the remarkably fast growth rate of UPEC that has been previously observed in infected patients. Source of Funding: AUA Fellowship, NIH award number R01 DK094777 Ann Arbor, MI; Winston-Salem, NC; Ann Arbor, MI© 2019 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 201Issue Supplement 4April 2019Page: e1046-e1046 Advertisement Copyright & Permissions© 2019 by American Urological Association Education and Research, Inc.MetricsAuthor Information Anna Sintsova* More articles by this author Ali Pirani More articles by this author Sargurunathan Subashchandrabose More articles by this author Evan Snitkin More articles by this author Harry L.T. Mobley More articles by this author Expand All Advertisement PDF downloadLoading ...

Key concepts: Escherichia coli, Virulence, Genitourinary system, Medicine, Urinary system, Microbiology, Gene, Immunology

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MP71-01 GENETICALLY DIVERSE UROPATHOGENIC ESCHERICHIA COLI ADOPT A COMMON TRANSCRIPTIONAL PROGRAM IN PATIENTS WITH URINARY TRACT INFECTIONS — Research Paper | ScholarLens