The E. coli Global Regulator DksA Reduces Transcription during T4 Infection

Patterson-West, Jennifer; James, Tamara D.; Fernández-Coll, Llorenç; Iben, James R.; Moon, Kyung Ho; Knipling, Leslie; Cashel, Michael; Hinton, Deborah M.

doi:10.3390/v10060308

Cited by 11 publications

(9 citation statements)

References 81 publications

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“…Thus, the observation of the changes in the lytic development efficiency of a given phage may have an explanation at one of these numerous steps. Interestingly, the lack of DksA in E. coli cells was also reported to affect T4 phage development, resulting in increased plaque size and a more productive infection [ 24 ], however, the mechanism involved was quite different than what we report here for phage P1 vir .…”

Section: Introductioncontrasting

confidence: 62%

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Virus–Host Interaction Gets Curiouser and Curiouser. PART I: Phage P1vir Enhanced Development in an E. coli DksA-Deficient Cell

Cech

Kłoska

Krause

et al. 2021

IJMS

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Bacteriophage P1 is among the best described bacterial viruses used in molecular biology. Here, we report that deficiency in the host cell DksA protein, an E. coli global transcription regulator, improves P1 lytic development. Using genetic and microbiological approaches, we investigated several aspects of P1vir biology in an attempt to understand the basis of this phenomenon. We found several minor improvements in phage development in the dksA mutant host, including more efficient adsorption to bacterial cell and phage DNA replication. In addition, gene expression of the main repressor of lysogeny C1, the late promoter activator Lpa, and lysozyme are downregulated in the dksA mutant. We also found nucleotide substitutions located in the phage immunity region immI, which may be responsible for permanent virulence of phage P1vir. We suggest that downregulation of C1 may lead to a less effective repression of lysogeny maintaining genes and that P1vir may be balancing between lysis and lysogeny, although finally it is able to enter the lytic pathway only. The mentioned improvements, such as more efficient replication and more “gentle” cell lysis, while considered minor individually, together may account for the phenomenon of a more efficient P1 phage development in a DksA-deficient host.

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Section: Introductioncontrasting

confidence: 62%

“…Interestingly, E. coli DksA deficiency was also reported to result in increased plaque size and a more productive infection by the T4 phage [ 24 ]. However, this phenomenon was accompanied by increased levels of early T4 transcripts, while in case of P1 vir development we observe DksA-dependent modulation of late gene expression.…”

Section: Resultsmentioning

confidence: 99%

Virus–Host Interaction Gets Curiouser and Curiouser. PART I: Phage P1vir Enhanced Development in an E. coli DksA-Deficient Cell

Cech

Kłoska

Krause

et al. 2021

IJMS

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“…In this system, PhRel encoded by a prophage protects Mycobacteria from infection by a second phage. Phage infection has previously been linked to alarmone accumulation and stringent response (37)(38)(39), although this may not be a universal response to infection (40). Presumably, alarmone accumulation is an example of a so-called abortive infection mechanism (41), where infected hosts are metabolically restricted, but the larger population is protected.…”

Section: Discussionmentioning

confidence: 99%

A widespread toxin−antitoxin system exploiting growth control via alarmone signaling

Jimmy

Saha

Kurata

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

207

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Under stressful conditions, bacterial RelA-SpoT Homolog (RSH) enzymes synthesize the alarmone (p)ppGpp, a nucleotide second messenger. (p)ppGpp rewires bacterial transcription and metabolism to cope with stress, and, at high concentrations, inhibits the process of protein synthesis and bacterial growth to save and redirect resources until conditions improve. Single-domain small alarmone synthetases (SASs) are RSH family members that contain the (p)ppGpp synthesis (SYNTH) domain, but lack the hydrolysis (HD) domain and regulatory C-terminal domains of the long RSHs such as Rel, RelA, and SpoT. We asked whether analysis of the genomic context of SASs can indicate possible functional roles. Indeed, multiple SAS subfamilies are encoded in widespread conserved bicistronic operon architectures that are reminiscent of those typically seen in toxin−antitoxin (TA) operons. We have validated five of these SASs as being toxic (toxSASs), with neutralization by the protein products of six neighboring antitoxin genes. The toxicity of Cellulomonas marina toxSAS FaRel is mediated by the accumulation of alarmones ppGpp and ppApp, and an associated depletion of cellular guanosine triphosphate and adenosine triphosphate pools, and is counteracted by its HD domain-containing antitoxin. Thus, the ToxSAS–antiToxSAS system with its multiple different antitoxins exemplifies how ancient nucleotide-based signaling mechanisms can be repurposed as TA modules during evolution, potentially multiple times independently.

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“…A study on the effects of (p)ppGpp into T4 phage infection seems to reach, indirectly, similar conclusions. T4 phage plaques in E. coli show an increase on plaque size in absence of either (p)ppGpp or DksA ( Patterson-West et al, 2018 ). Although DksA affected T4 gene expression, (p)ppGpp had almost no effect on the phage gene expression, suggesting that its effects on plaque size are related to effects in the host rather than the phage, which could be attributed to an increased membrane fragility in absence of (p)ppGpp ( Patterson-West et al, 2018 ).…”

Section: Effects Of Basal Levels Of (P)ppgpp In Escherichiamentioning

confidence: 99%

Possible Roles for Basal Levels of (p)ppGpp: Growth Efficiency Vs. Surviving Stress

Fernández-Coll

Cashel

2020

Front. Microbiol.

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Two (p)ppGpp nucleotide analogs, sometimes abbreviated simply as ppGpp, are widespread in bacteria and plants. Their name alarmone reflects a view of their function as intracellular hormone-like protective alarms that can increase a 100-fold when sensing any of an array of physical or nutritional dangers, such as abrupt starvation, that trigger lifesaving adjustments of global gene expression and physiology. The diversity of mechanisms for stress-specific adjustments of this sort is large and further compounded by almost infinite microbial diversity. The central question raised by this review is whether the small basal levels of (p)ppGpp functioning during balanced growth serve very different roles than alarmone-like functions. Recent discoveries that abrupt amino acid starvation of Escherichia coli , accompanied by very high levels of ppGpp, occasion surprising instabilities of transfer RNA (tRNA), ribosomal RNA (rRNA), and ribosomes raises new questions. Is this destabilization, a mode of regulation linearly related to (p)ppGpp over the entire continuum of (p)ppGpp levels, including balanced growth? Are regulatory mechanisms exerted by basal (p)ppGpp levels fundamentally different than for high levels? There is evidence from studies of other organisms suggesting special regulatory features of basal levels compared to burst of (p)ppGpp. Those differences seem to be important even during bacterial infection, suggesting that unbalancing the basal levels of (p)ppGpp may become a future antibacterial treatment. A simile for this possible functional duality is that (p)ppGpp acts like a car’s brake, able to stop to avoid crashes as well as to slow down to drive safely.

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The E. coli Global Regulator DksA Reduces Transcription during T4 Infection

Cited by 11 publications

References 81 publications

Virus–Host Interaction Gets Curiouser and Curiouser. PART I: Phage P1vir Enhanced Development in an E. coli DksA-Deficient Cell

Virus–Host Interaction Gets Curiouser and Curiouser. PART I: Phage P1vir Enhanced Development in an E. coli DksA-Deficient Cell

A widespread toxin−antitoxin system exploiting growth control via alarmone signaling

Possible Roles for Basal Levels of (p)ppGpp: Growth Efficiency Vs. Surviving Stress

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