Survival of the drowsiest: the hibernating 100S ribosome in bacterial stress management

Gohara, David W.; Yap, Mee-Ngan Frances

doi:10.1007/s00294-017-0796-2

Cited by 66 publications

(54 citation statements)

References 59 publications

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“…S. aureus HPF is one of the predominant proteins induced upon host cell internalization and during infections (13,14). For reviews of the topic, see references (15)(16)(17)(18)(19).…”

Section: Introductionmentioning

confidence: 99%

The hibernating 100S complex is a target of ribosome-recycling factor and elongation factor G in Staphylococcus aureus

Basu

Shields

Yap

2020

Journal of Biological Chemistry

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The formation of translationally inactive 70S dimers (called 100S ribosomes) by hibernation-promoting factor is a widespread survival strategy among bacteria. Ribosome dimerization is thought to be reversible, with the dissociation of the 100S complexes enabling ribosome recycling for participation in new rounds of translation. The precise pathway of 100S ribosome recycling has been unclear. We previously found that the heat-shock GTPase HflX in the human pathogen Staphylococcus aureus is a minor disassembly factor. Cells lacking hflX do not accumulate 100S ribosomes unless they are subjected to heat exposure, suggesting the existence of an alternative pathway during nonstressed conditions. Here, we provide biochemical and genetic evidence that two essential translation factors, ribosome-recycling factor (RRF) and GTPase elongation factor G (EF-G), synergistically split 100S ribosomes in a GTP-dependent but tRNA translocation-independent manner. We found that although HflX and the RRF/EF-G pair are functionally interchangeable, HflX is expressed at low levels and is dispensable under normal growth conditions. The bacterial RRF/EF-G pair was previously known to target only the post-termination 70S complexes; our results reveal a new role in the reversal of ribosome hibernation that is intimately linked to bacterial pathogenesis, persister formation, stress responses, and ribosome integrity.

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“…S. aureus HPF is one of the predominant proteins induced upon host cell internalization and during infections (13,14). For reviews of the topic, see references (15)(16)(17)(18)(19).…”

Section: Introductionmentioning

confidence: 99%

The hibernating 100S complex is a target of ribosome-recycling factor and elongation factor G in Staphylococcus aureus

Basu

Shields

Yap

2020

Journal of Biological Chemistry

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“…This process benefits from the ribosomal internal flexibility, which is needed for protein synthesis processivity [5], and has been observed in bacterial, plastids [6-10] and mammalian cells [11]. It has been shown that in S. aureus, 100S complexes are disassembled by a GTPase HflX under heat stress and a hitherto unknown major dissociation factor [17,18]. The importance of the dimer formation for cell survival has been demonstrated in several systems.…”

Section: Introductionmentioning

confidence: 99%

“…Ribosome hibernation is a reversible process. It has been shown that in S. aureus, 100S complexes are disassembled by a GTPase HflX under heat stress and a hitherto unknown major dissociation factor [17,18]. A minor, yet clinically important group of Gram-negative bacteria (c-proteobacteria) that includes Escherichia coli, Salmonella typhimurium, Yersinia pestis and Pseudomonas aeruginosa, carries a shorter form of HPF (HPF short ).…”

Section: Introductionmentioning

confidence: 99%

Stress response as implemented by hibernating ribosomes: a structural overview

et al. 2019

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Protein synthesis is one of the most energy demanding cellular processes. The ability to regulate protein synthesis is essential for cells under normal as well as stress conditions, such as nutrient deficiencies. One mechanism for protein synthesis suppression is the dimerization of ribosomes into hibernation complexes. In most cells, this process is promoted by the hibernating promoting factor (HPF) and in a small group of Gram‐negative bacteria (γ‐proteobacteria), the dimer formation is induced by a shorter version of HPF (HPFshort) and by an additional protein, the ribosome modulation factor. In most bacteria, the product of this process is the 100S ribosome complex. Recent advances in cryogenic electron microscopy methods resulted in an abundance of detailed structures of near atomic resolutions 100S complexes that allow for a better understanding of the dimerization process and the way it inhibits protein synthesis. As ribosomal dimerization is vital for cell survival, this process is an attractive target for the development of novel antimicrobial substances that might inhibit or stabilize the complex formation. As different dimerization processes exist among bacteria, including pathogens, this process may provide the basis for species‐specific design of antimicrobial agents. Here, we review in detail the various dimerization mechanisms and discuss how they affect the overall dimer structures of the bacterial ribosomes.

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“…Regulation of ribosome function is known to have a key role in bacterial persistence (Prossliner et al, 2018); therefore, we next analyzed relative abundance and label incorporation of all detected ribosomal proteins, as well as ribosome-associated hibernation and stationary phase factors proposed to modulate ribosomal activity, such as EttA, RaiA, ElaB, YqjD and Sra (Gohara and Yap, 2018;Prossliner et al, 2018;Yoshida and Wada, 2014). In persisting cells, measured rates of label incorporation and relative abundances of most ribosomal proteins were relatively high (Figure 2A).…”

Section: Ribosome-associated Proteins Raia and Sra Show Elevated Syntmentioning

confidence: 99%

Proteome dynamics during antibiotic persistence and resuscitation

Šemanjski

Gratani

Englert

et al. 2020

Preprint

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Bacterial persister cells become transiently tolerant to antibiotics by restraining their growth and metabolic activity. Detailed molecular characterization of bacterial persistence is hindered by low count of persisting cells and the need for their isolation. Here we used sustained addition of stable isotope-labeled lysine to selectively label the proteome of hipA-induced persisting and hipB-induced resuscitating E. coli cells in minimal medium after antibiotic treatment. Timeresolved, 24-hour measurement of label incorporation allowed detection of over 500 newly synthetized proteins in persister cells, demonstrating low but widespread protein synthesis. Many essential proteins were newly synthesized and several ribosome-associated proteins showed unusually high synthesis levels, pointing to their roles in maintenance of persistence. At the onset of resuscitation, cells synthesized ABC transporters, restored translation machinery and resumed metabolism by inducing glycolysis and biosynthesis of amino acids. This dataset provides an unprecedented insight into the processes governing persistence and resuscitation of bacterial cells.

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Survival of the drowsiest: the hibernating 100S ribosome in bacterial stress management

Cited by 66 publications

References 59 publications

The hibernating 100S complex is a target of ribosome-recycling factor and elongation factor G in Staphylococcus aureus

The hibernating 100S complex is a target of ribosome-recycling factor and elongation factor G in Staphylococcus aureus

Stress response as implemented by hibernating ribosomes: a structural overview

Proteome dynamics during antibiotic persistence and resuscitation

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