The ObgE/CgtA GTPase influences the stringent response to amino acid starvation in <i>Escherichia coli</i>

Persky, Nicole S.; Ferullo, Daniel J.; Cooper, Deani L.; Moore, Hayley R.; Lovett, Susan T.

doi:10.1111/j.1365-2958.2009.06767.x

Cited by 75 publications

(81 citation statements)

References 55 publications

(109 reference statements)

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“…B. subtilis Obg shares a C-terminal TGS (threonyltRNA synthetase ThrRS, GTPase and SpoT) domain with SpoT, and (p)ppGpp was found in the active site of crystallized Obg (Buglino et al, 2002). Moreover, Obg was demonstrated to bind (p)ppGpp with biologically relevant affinity (Persky et al, 2009;Kanjee et al, 2012). E. coli Obg interacts with SpoT, but not with RelA (Wout et al, 2004;Raskin et al, 2007), and depletion of Obg results in increased levels of (p)ppGpp (Jiang et al, 2007).…”

Section: Obg-mediated Persistence Requires (P)ppgpp and Hokbmentioning

confidence: 95%

“…E. coli Obg interacts with SpoT, but not with RelA (Wout et al, 2004;Raskin et al, 2007), and depletion of Obg results in increased levels of (p)ppGpp (Jiang et al, 2007). Furthermore, Obg was reported to alter the pppGpp/ ppGpp ratio during amino acid starvation (Persky et al, 2009). Finally, Obg was recently described as an anti-association factor that inhibits formation of the 70S ribosome upon binding with (p)ppGpp.…”

Section: Obg-mediated Persistence Requires (P)ppgpp and Hokbmentioning

confidence: 96%

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Obg and Membrane Depolarization Are Part of a Microbial Bet-Hedging Strategy that Leads to Antibiotic Tolerance

et al. 2015

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Within bacterial populations, a small fraction of persister cells is transiently capable of surviving exposure to lethal doses of antibiotics. As a bet-hedging strategy, persistence levels are determined both by stochastic induction and by environmental stimuli called responsive diversification. Little is known about the mechanisms that link the low frequency of persisters to environmental signals. Our results support a central role for the conserved GTPase Obg in determining persistence in Escherichia coli in response to nutrient starvation. Obg-mediated persistence requires the stringent response alarmone (p)ppGpp and proceeds through transcriptional control of the hokB-sokB type I toxin-antitoxin module. In individual cells, increased Obg levels induce HokB expression, which in turn results in a collapse of the membrane potential, leading to dormancy. Obg also controls persistence in Pseudomonas aeruginosa and thus constitutes a conserved regulator of antibiotic tolerance. Combined, our findings signify an important step toward unraveling shared genetic mechanisms underlying persistence.

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Section: Obg-mediated Persistence Requires (P)ppgpp and Hokbmentioning

confidence: 95%

Section: Obg-mediated Persistence Requires (P)ppgpp and Hokbmentioning

confidence: 96%

Obg and Membrane Depolarization Are Part of a Microbial Bet-Hedging Strategy that Leads to Antibiotic Tolerance

et al. 2015

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“…Based on synergy with recombination proteins, the investigators proposed that ObgE action prevents the accumulation of regressed forks and DNA breaks during the inhibition of replication. Subsequently, ObgE was found to bind ppGpp at physiologically relevant concentrations in vitro, and inactivation of ObgE activity was shown to increase the pppGpp to ppGpp ratio in vivo during the stringent response (Persky et al 2009). …”

Section: Checkpoints Relating To Stringent Responsementioning

confidence: 99%

DNA Damage Responses in Prokaryotes: Regulating Gene Expression, Modulating Growth Patterns, and Manipulating Replication Forks

Kreuzer

2013

Cold Spring Harbor Perspectives in Biology

208

185

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Recent advances in the area of bacterial DNA damage responses are reviewed here. The SOS pathway is still the major paradigm of bacterial DNA damage response, and recent studies have clarified the mechanisms of SOS induction and key physiological roles of SOS including a very major role in genetic exchange and variation. When considering diverse bacteria, it is clear that SOS is not a uniform pathway with one purpose, but rather a platform that has evolved for differing functions in different bacteria. Relating in part to the SOS response, the field has uncovered multiple apparent cell-cycle checkpoints that assist cell survival after DNA damage and remarkable pathways that induce programmed cell death in bacteria. Bacterial DNA damage responses are also much broader than SOS, and several important examples of LexA-independent regulation will be reviewed. Finally, some recent advances that relate to the replication and repair of damaged DNA will be summarized. Since the publication of DNA Repair and Mutagenesis in 2006 (Friedberg et al. 2006), our understanding of bacterial DNA damage responses has progressed significantly. Some studies have refined known pathways and filled in important details, whereas other studies have uncovered surprising new pathways such as bacterial programmed cell death and a form of replicative repair that reconstitutes severely shattered genomes. This review will focus on these recent advances, with only limited discussion and citation to work that precedes the 2006 tome. THE SOS RESPONSEAs scientists have studied the SOS response in Escherichia coli and other bacteria over the last decade, our understanding of SOS has changed in unexpected ways and the pathway has been found integrated in diverse cellular processes. Our understanding of the mechanism of SOS induction has also advanced in recent years, including a view of induction at the single-cell level. A surprising finding is that the functions of the SOS pathway are not uniform between bacterial species, and so the view of SOS as

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“…In Salmonella enterica serovar Typhimurium, ppGpp interacts with SlyA, a transcriptional activator of this pathogen's intracellular virulence program, facilitating its dimerization and binding to target promoters (223). In both E. coli and B. subtilis, ppGpp interacts with Obg, a nucleotide binding protein implicated in a number of physiological processes (33,156). In V. cholerae, the ribosome-associated Obg homologue ("CgtA") appears to regulate ppGpp synthesis.…”

Section: Regulatory Targets Of Ppgppmentioning

confidence: 99%

ppGpp Conjures Bacterial Virulence

Dalebroux

Svensson

Gaynor

et al. 2010

Microbiol Mol Biol Rev

334

364

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SUMMARY Like for all microbes, the goal of every pathogen is to survive and replicate. However, to overcome the formidable defenses of their hosts, pathogens are also endowed with traits commonly associated with virulence, such as surface attachment, cell or tissue invasion, and transmission. Numerous pathogens couple their specific virulence pathways with more general adaptations, like stress resistance, by integrating dedicated regulators with global signaling networks. In particular, many of nature's most dreaded bacteria rely on nucleotide alarmones to cue metabolic disturbances and coordinate survival and virulence programs. Here we discuss how components of the stringent response contribute to the virulence of a wide variety of pathogenic bacteria.

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The ObgE/CgtA GTPase influences the stringent response to amino acid starvation in Escherichia coli

Cited by 75 publications

References 55 publications

Obg and Membrane Depolarization Are Part of a Microbial Bet-Hedging Strategy that Leads to Antibiotic Tolerance

Obg and Membrane Depolarization Are Part of a Microbial Bet-Hedging Strategy that Leads to Antibiotic Tolerance

DNA Damage Responses in Prokaryotes: Regulating Gene Expression, Modulating Growth Patterns, and Manipulating Replication Forks

ppGpp Conjures Bacterial Virulence

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