TY - INPR A1 - Khusainov, Iskander A1 - Romanov, Natalie A1 - Goemans, Camille A1 - Turoňová, Beata A1 - Zimmerli, Christian Eugen A1 - Welsch, Sonja A1 - Langer, Julian David A1 - Typas, Athanasios A1 - Beck, Martin T1 - The killing of human gut commensal E. coli ED1a by tetracycline is associated with severe ribosome dysfunction T2 - bioRxiv N2 - Ribosomes translate the genetic code into proteins. Recent technical advances have facilitated in situ structural analyses of ribosome functional states inside eukaryotic cells and the minimal bacterium Mycoplasma. However, such analyses of Gram-negative bacteria are lacking, despite their ribosomes being major antimicrobial drug targets. Here we compare two E. coli strains, a lab E. coli K-12 and human gut isolate E. coli ED1a, for which tetracycline exhibits bacteriostatic and bactericidal action, respectively. The in situ ribosome structures upon tetracycline treatment show a virtually identical drug binding-site in both strains, yet the distribution of ribosomal complexes clearly differs. While K-12 retains ribosomes in a translation competent state, tRNAs are lost in the vast majority of ED1a ribosomes. A differential response is also reflected in proteome-wide abundance and thermal stability assessment. Our study underlines the need to include molecular analyses and to consider gut bacteria when addressing antibiotic mode of action. Y1 - 2023 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/74783 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-747835 IS - 2023.07.06.546847 ER -