Abstract:
: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.
journal_name
Environ Microbioljournal_title
Environmental microbiologyauthors
Song S,Wood TKdoi
10.1111/1462-2920.14828subject
Has Abstractpub_date
2020-03-01 00:00:00pages
850-857issue
3eissn
1462-2912issn
1462-2920journal_volume
22pub_type
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