Basu et al. 2016 (PRJNA299306)

General Details

Title Ribosome hibernation factor promotes Staphyloccocal survival and differentially represses translation
Organism
Number of Samples 43
Release Date 2015/10/20 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP065033
ENA SRP065033
GEO GSE74197
BioProject PRJNA299306

Publication

Title
Authors Basu A, Shields KE, Eickhoff CS, Hoft DF, Yap MN
Journal Journal of bacteriology
Publication Date 2018 Dec 15
Abstract The translationally silent 100S ribosome is a poorly understood form of the dimeric 70S complex that is ubiquitously found in all bacterial phyla. The elimination of the hibernating 100S ribosome leads to translational derepression, ribosome instability, antibiotic sensitivity, and biofilm defects in some bacteria. In Firmicutes , such as the opportunistic pathogen Staphylococcus aureus , a 190-amino acid protein called h ibernating- p romoting f actor (HPF) dimerizes and conjoins two 70S ribosomes through a direct interaction between the HPF homodimer, with each HPF monomer tethered on an individual 70S complex. While the formation of the 100S ribosome in gammaproteobacteria and cyanobacteria is exclusively induced during postexponential growth phase and darkness, respectively, the 100S ribosomes in Firmicutes are constitutively produced from the lag-logarithmic phase through the post-stationary phase. Very little is known about the regulatory pathways that control hpf expression and 100S ribosome abundance. Here, we show that a general stress response (GSR) sigma factor (SigB) and a GTP-sensing transcription factor (CodY) integrate nutrient and thermal signals to regulate hpf synthesis in S. aureus , resulting in an enhanced virulence of the pathogen in a mouse model of septicemic infection. CodY-dependent regulation of hpf is strain specific. An epistasis analysis further demonstrated that CodY functions upstream of the GSR pathway in a condition-dependent manner. The results reveal an important link between S. aureus stress physiology, ribosome metabolism, and infection biology. IMPORTANCE The dimerization of 70S ribosomes (100S complex) plays an important role in translational regulation and infectivity of the major human pathogen Staphylococcus aureus Although the dimerizing factor HPF has been characterized biochemically, the pathways that regulate 100S ribosome abundance remain elusive. We identified a metabolite- and nutrient-sensing transcription factor, CodY, that serves both as an activator and a repressor of hpf expression in nutrient- and temperature-dependent manners. Furthermore, CodY-mediated activation of hpf masks a secondary hpf transcript derived from a general stress response SigB promoter. CodY and SigB regulate a repertoire of virulence genes. The unexpected link between ribosome homeostasis and the two master virulence regulators provides new opportunities for alternative druggable sites. Copyright © 2018 Basu et al.
PMC PMC6256015
PMID 30297357
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR2733429 PRJNA299306 Staphylococcus aureus 0.0 Ribo-Seq 0.0
SRR2733430 PRJNA299306 Staphylococcus aureus 0.0 Ribo-Seq 0.0
SRR2733433 PRJNA299306 Staphylococcus aureus 0.0 Ribo-Seq 0.0
SRR2733434 PRJNA299306 Staphylococcus aureus 0.0 Ribo-Seq 0.0
SRR2733437 PRJNA299306 Staphylococcus aureus 0.0 RNA-Seq 0.0
SRR2733438 PRJNA299306 Staphylococcus aureus 0.0 RNA-Seq 0.0
SRR2733441 PRJNA299306 Staphylococcus aureus 0.0 RNA-Seq 0.0
SRR2733442 PRJNA299306 Staphylococcus aureus 0.0 RNA-Seq 0.0
SRR2733445 PRJNA299306 Staphylococcus aureus 0.0 Ribo-Seq 0.0
SRR2733446 PRJNA299306 Staphylococcus aureus 0.0 Ribo-Seq 0.0
SRR2733449 PRJNA299306 Staphylococcus aureus 0.0 Ribo-Seq 0.0
SRR2733450 PRJNA299306 Staphylococcus aureus 0.0 Ribo-Seq 0.0
SRR2733453 PRJNA299306 Staphylococcus aureus 0.0 RNA-Seq 0.0
SRR2733454 PRJNA299306 Staphylococcus aureus 0.0 RNA-Seq 0.0
SRR2733457 PRJNA299306 Staphylococcus aureus 0.0 RNA-Seq 0.0
SRR2733458 PRJNA299306 Staphylococcus aureus 0.0 RNA-Seq 0.0
SRR2733461 PRJNA299306 Staphylococcus aureus 0.0 Ribo-Seq 0.0
SRR2733462 PRJNA299306 Staphylococcus aureus 0.0 Ribo-Seq 0.0
SRR2733465 PRJNA299306 Staphylococcus aureus 0.0 Ribo-Seq 0.0
SRR2733466 PRJNA299306 Staphylococcus aureus 0.0 RNA-Seq 0.0
SRR2733469 PRJNA299306 Staphylococcus aureus 0.0 RNA-Seq 0.0
SRR2733470 PRJNA299306 Staphylococcus aureus 0.0 RNA-Seq 0.0
SRR2733473 PRJNA299306 Staphylococcus aureus 0.0 Ribo-Seq 0.0
SRR2733474 PRJNA299306 Staphylococcus aureus 0.0 Ribo-Seq 0.0
SRR2733477 PRJNA299306 Staphylococcus aureus 0.0 RNA-Seq 0.0
SRR2733478 PRJNA299306 Staphylococcus aureus 0.0 RNA-Seq 0.0
SRR2733481 PRJNA299306 Staphylococcus aureus 0.0 RNA-Seq 0.0
SRR2733482 PRJNA299306 Staphylococcus aureus 0.0 RNA-Seq 0.0
SRR2733431 PRJNA299306 Staphylococcus aureus 0.0 Ribo-Seq 0.0
SRR2733432 PRJNA299306 Staphylococcus aureus 0.0 Ribo-Seq 0.0
SRR2733435 PRJNA299306 Staphylococcus aureus 0.0 Ribo-Seq 0.0
SRR2733436 PRJNA299306 Staphylococcus aureus 0.0 Ribo-Seq 0.0
SRR2733447 PRJNA299306 Staphylococcus aureus 0.0 Ribo-Seq 0.0
SRR2733448 PRJNA299306 Staphylococcus aureus 0.0 Ribo-Seq 0.0
SRR2733451 PRJNA299306 Staphylococcus aureus 0.0 Ribo-Seq 0.0
SRR2733452 PRJNA299306 Staphylococcus aureus 0.0 Ribo-Seq 0.0
SRR2733460 PRJNA299306 Staphylococcus aureus 0.0 Ribo-Seq 0.0
SRR2733463 PRJNA299306 Staphylococcus aureus 0.0 Ribo-Seq 0.0
SRR2733464 PRJNA299306 Staphylococcus aureus 0.0 Ribo-Seq 0.0
SRR2733471 PRJNA299306 Staphylococcus aureus 0.0 Ribo-Seq 0.0
SRR2733472 PRJNA299306 Staphylococcus aureus 0.0 Ribo-Seq 0.0
SRR2733475 PRJNA299306 Staphylococcus aureus 0.0 Ribo-Seq 0.0
SRR2733476 PRJNA299306 Staphylococcus aureus 0.0 Ribo-Seq 0.0
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)

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