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Persister cells resuscitate via ribosome modification by 23S rRNA pseudouridine synthase RluD
Author(s) -
Song Sooyeon,
Wood Thomas K.
Publication year - 2020
Publication title -
environmental microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.954
H-Index - 188
eISSN - 1462-2920
pISSN - 1462-2912
DOI - 10.1111/1462-2920.14828
Subject(s) - ribosome , biology , pseudouridine , 23s ribosomal rna , escherichia coli , ribosomal rna , resuscitation , protein biosynthesis , atp synthase , biochemistry , microbiology and biotechnology , rna , transfer rna , gene , medicine , emergency medicine
Summary Upon a wide range of stress conditions (e.g. nutrient, antibiotic, oxidative), a subpopulation of bacterial cells known as persisters survives by halting metabolism. These cells resuscitate rapidly to reconstitute infections once the stress is removed and nutrients are provided. However, how these dormant cells resuscitate is not understood well but involves reactivating ribosomes. By screening 10,000 compounds directly for stimulating Escherichia coli persister cell resuscitation, we identified that 2‐{[2‐(4‐bromophenyl)‐2‐oxoethyl]thio}‐3‐ethyl‐5,6,7,8‐tetrahydro[1]benzothieno[2,3‐d]pyrimidin‐4(3H)‐one (BPOET) stimulates resuscitation. Critically, by screening 4267 E. coli proteins, we determined that BPOET activates hibernating ribosomes via 23S rRNA pseudouridine synthase RluD, which increases ribosome activity. Corroborating the increased waking with RluD, production of RluD increased the number of active ribosomes in persister cells. Also, inactivating the small RNA RybB which represses rluD led to faster persister resuscitation. Hence, persister cells resuscitate via activation of RluD.