Post-segregational Killing and Phage Inhibition Are Not Mediated by Cell Death Through Toxin/Antitoxin Systems

Song, Sooyeon; Wood, Thomas K.

doi:10.3389/fmicb.2018.00814

Cited by 88 publications

(65 citation statements)

References 62 publications

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“…For example, in the second report of a TA system (Hok/Sok) “post‐segregational killing” was claimed for the TA system Hok/Soks [ 14 ] but there is no evidence of it. [ 15 ] Furthermore, the claim of programmed cell death by MazF [ 16,17 ] is not warranted. [ 18–21 ] Similarly, the claim of phage inhibition by altruistic host death [ 22,23 ] is not warranted.…”

Section: Reviewmentioning

confidence: 99%

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Toxin/Antitoxin System Paradigms: Toxins Bound to Antitoxins Are Not Likely Activated by Preferential Antitoxin Degradation

Song

Wood

2020

Adv. Biosys.

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Periodically, a scientific field should examine its early premises. For ubiquitous toxin/antitoxin (TA) systems, several initial paradigms require adjustment based on accumulated data. For example, it is now clear that under physiological conditions, there is little evidence that toxins of TA systems cause cell death and little evidence that TA systems cause persistence. Instead, TA systems are utilized to reduce metabolism during stress, inhibit phages, stabilize genetic elements, and influence biofilm formation (bacterial cells attached via an extracellular matrix). In this essay, it is argued that toxins bound to antitoxins are not likely to become activated by preferential antitoxin degradation but instead, de novo toxin synthesis in the absence of stoichiometric amounts of antitoxin activates toxins.

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Section: Reviewmentioning

confidence: 99%

“…[ 18–21 ] Similarly, the claim of phage inhibition by altruistic host death [ 22,23 ] is not warranted. [ 15 ] Therefore, there is no evidence linking TA systems with cell death under physiological conditions.…”

Section: Reviewmentioning

confidence: 99%

Toxin/Antitoxin System Paradigms: Toxins Bound to Antitoxins Are Not Likely Activated by Preferential Antitoxin Degradation

Song

Wood

2020

Adv. Biosys.

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“…). Since virtually all cells experience nutrient stress (Song and Wood ) and since the viable but not culturable state appears to be the same as the persister state (Kim et al . ), persistence may be a universal phenotype that is the key to microbial survival.…”

Section: Introductionmentioning

confidence: 99%

“…Also, both antibiotic and nutrient stress creates persister cells (Bernier et al 2013;Maisonneuve and Gerdes 2014;Martins et al 2018). Since virtually all cells experience nutrient stress (Song and Wood 2018) and since the viable but not culturable state appears to be the same as the persister state (Kim et al 2018b), persistence may be a universal phenotype that is the key to microbial survival.…”

Section: Introductionmentioning

confidence: 99%

Interkingdom signal indole inhibits Pseudomonas aeruginosa persister cell waking

et al. 2019

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Aims Persister cells are stressed cells that have transient tolerance to antibiotics; these cells undergo no genetic change, but instead, their tolerance is due to reduced metabolism. Unfortunately, little is known about how persisters resuscitate, so we explored the waking of cells in the presence of the interkingdom signal indole. Methods and Results To generate a large population of persister cells, we induced the persister phenotype in the opportunistic pathogen Pseudomonas aeruginosa by pretreating cells with carbonyl cyanide m‐chlorophenylhydrazone to reduce translation by depleting ATP levels, and found, via single cell observations, that proline is sufficient to wake the persister cells. P. aeruginosa is often present in the gastrointestinal tract, and indole from commensal bacteria such as Escherichia coli has been shown to inhibit P. aeruginosa quorum sensing and pathogenicity without influencing growth. Furthermore, indole is not toxic to P. aeruginosa persister cells. However, we find here that physiological concentrations of indole inhibit P. aeruginosa persister cell resuscitation with an efficiency of higher than 95%. Critically, when contacted with E. coli stationary‐phase cultures, the indole produced by E. coli completely inhibits persister cell resuscitation of P. aeruginosa. Conclusions Therefore, E. coli has devised a method to outcompete its competitors by preventing their resuscitation with indole. Significance and Impact of the Study This work provides insight into why indole is produced by commensal bacteria.

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“…SocB/SocA), the antitoxin protein facilitates toxin degradation as an adaptor protein (Page and Peti, 2016). Recently, the type VII system has been described (Hha/TomB) in which the antitoxin is an enzyme that inactivates the toxin by oxidizing a cysteine residue (Marimon et al, 2016;Song and Wood, 2018).…”

Section: Introductionmentioning

confidence: 99%

Toxins of toxin/antitoxin systems are inactivated primarily through promoter mutations

Fernández‐García

Kim

Tomás

et al. 2019

Journal of Applied Microbiology

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Aims Given the extreme toxicity of some of the toxins of toxin‐antitoxin (TA) systems, we were curious how the cell silences toxins, if the antitoxin is inactivated or independent toxins are obtained via horizontal gene transfer. Methods and Results Growth curves of Escherichia coli K12 BW25113 harbouring plasmid pCA24N to produce RalR, MqsR, GhoT or Hha toxins, showed toxin inactivation after 3 h. Sequencing plasmids from these cultures revealed toxin inactivation occurred primarily due to consistent deletions in the promoter. The lack of mutation in the structural genes was corroborated by a bioinformatics analysis of 1000 E. coli genomes which showed both conservation and little variability in the four toxin genes. For those strains that lacked a mutation in the plasmid, single nucleotide polymorphism analysis was performed to identify that chromosomal mutations iraM and mhpR inactivate the toxins GhoT and MqsR/GhoT respectively. Conclusion We find that the RalR (type I), MqsR (type II), GhoT (type V) and Hha (type VII) toxins are inactivated primarily by a mutation that inactivates the toxin promoter or via the chromosomal mutations iraM and mhpR. Significance and Impact of the Study This study demonstrates toxins of TA systems may be inactivated by mutations that primarily affect the toxin gene promoter instead of the toxin structural gene.

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Post-segregational Killing and Phage Inhibition Are Not Mediated by Cell Death Through Toxin/Antitoxin Systems

Cited by 88 publications

References 62 publications

Toxin/Antitoxin System Paradigms: Toxins Bound to Antitoxins Are Not Likely Activated by Preferential Antitoxin Degradation

Toxin/Antitoxin System Paradigms: Toxins Bound to Antitoxins Are Not Likely Activated by Preferential Antitoxin Degradation

Interkingdom signal indole inhibits Pseudomonas aeruginosa persister cell waking

Toxins of toxin/antitoxin systems are inactivated primarily through promoter mutations

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