TY - JOUR
T1 - Persister cells resuscitate via ribosome modification by 23S rRNA pseudouridine synthase RluD
AU - Song, Sooyeon
AU - Wood, Thomas K.
N1 - Funding Information:
This work was supported by funds derived from the Biotechnology Endowed Professorship at the Pennsylvania State University. We are grateful for the rybB mutant provided by Dr. Gisela Storz.
Publisher Copyright:
© 2019 Society for Applied Microbiology and John Wiley & Sons Ltd.
PY - 2020/3/1
Y1 - 2020/3/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85075907965&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85075907965&partnerID=8YFLogxK
U2 - 10.1111/1462-2920.14828
DO - 10.1111/1462-2920.14828
M3 - Article
C2 - 31608580
AN - SCOPUS:85075907965
SN - 1462-2912
VL - 22
SP - 850
EP - 857
JO - Environmental microbiology
JF - Environmental microbiology
IS - 3
ER -