MP25-04 IDENTIFYING METABOLIC AND GENOMIC SIGNATURES AS BIOMARKERS FOR UROPATHOGENIC E COLI AND ASYMPTOMATIC BACTERIURIA

Abstract

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder I (MP25)1 Sep 2021MP25-04 IDENTIFYING METABOLIC AND GENOMIC SIGNATURES AS BIOMARKERS FOR UROPATHOGENIC E COLI AND ASYMPTOMATIC BACTERIURIA Benjamin Abelson, Grace Morales, Gerald Van Horn, Allison R Eberly, Douglass B Clayton, Jonathan E Schmitz, and Maria Hadjifrangiskou Benjamin AbelsonBenjamin Abelson More articles by this author , Grace MoralesGrace Morales More articles by this author , Gerald Van HornGerald Van Horn More articles by this author , Allison R EberlyAllison R Eberly More articles by this author , Douglass B ClaytonDouglass B Clayton More articles by this author , Jonathan E SchmitzJonathan E Schmitz More articles by this author , and Maria HadjifrangiskouMaria Hadjifrangiskou More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002022.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Uropathogenic Escherichia coli (UPEC) is the most common cause of cystitis, though the presence of E. coli in urine does not universally cause symptoms. We aim to identify the metabolic and genomic signatures of E. coli isolates that distinguish cystitis-causing strains from E. coli strains present in asymptomatic bacteriuria (ASB). METHODS: We used a biobank to identify E. coli isolates from adult patients. The cohort was divided into cystitis strains and asymptomatic bacteriuria strains based on medical record review. A subset of these isolates were grown in pooled human urine under hypoxic conditions and then subjected to global metabolomics. For genomic sequencing, isolates were grown overnight in lysogeny broth, samples pelleted then subjected to genomic DNA isolation, whole-genome sequencing and analysis. RESULTS: Pooled metabolomic analysis of a subset of 26 ASB and 77 cystitis isolates demonstrates lower levels of guanosine but higher levels of adenosine in the supernatant of asymptomatic bacteriuria E. coli isolates. Given that both metabolites are implicated in purine metabolism, this supplements previously published work from our group demonstrating that purine biosynthesis is necessary for uropathogenic E. coli survival with bladder urothelial cells. 138 isolates were processed for genomic analysis. This included isolates from 126 women (91.6%) and 68 (49.3%) cystitis strains. Our development of a reproducible pipeline for urinary bacterial isolate whole genome sequencing and gene assembly demonstrates the feasibility for developing continued translational analysis to examine clinical specimens for genomic signatures. Genomic analysis of known purine synthesis-related genes did demonstrate single nucleotide polymorphisms (SNPs) that may alter single amino acids, but these results did not cluster based on the clinical presentation of the isolate source. CONCLUSIONS: UPEC differ from strains isolated from patients with asymptomatic bacteria in terms of the levels of purine synthesis metabolites, though examination of known purine synthesis gene SNPs does not reveal clustering based on clinical data. Further work using genome wide association studies to identify SNPs in non-coding regions along with additional metagenomics studies will be needed to identify further metabolic and genomic signatures that differentiate uropathogenic E. coli from asymptomatic strains. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e454-e455 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Benjamin Abelson More articles by this author Grace Morales More articles by this author Gerald Van Horn More articles by this author Allison R Eberly More articles by this author Douglass B Clayton More articles by this author Jonathan E Schmitz More articles by this author Maria Hadjifrangiskou More articles by this author Expand All Advertisement Loading ...