Toxin-antitoxin systems and their medical applications: current status and future perspective

Srivastav, Ajeet K.; Pati, Soumya; Kaushik, Himani; Singh, Shailja; Garg, Lalit C.

doi:10.1007/s00253-021-11134-z

Cited by 28 publications

(15 citation statements)

References 166 publications

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“…Toxin-antitoxin (TA) systems are genetic modules that are frequently found on bacterial chromosomes and plasmids ( Pandey and Gerdes, 2005 ; Leplae et al, 2011 ; Harms et al, 2018 ; Srivastava et al, 2021 ; Jurėnas et al, 2022 ). TA systems typically consist of two factors: a toxin protein that has an inhibitory or poisonous effect on the host organism and an antitoxin that either counteracts expression of the toxin or antagonizes toxin activity ( Page and Peti, 2016 ; Harms et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

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A Shift in Perspective: A Role for the Type I Toxin TisB as Persistence-Stabilizing Factor

Edelmann

Berghoff

2022

Front. Microbiol.

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Bacterial persistence is a phenomenon that is founded by the existence of a subpopulation of multidrug-tolerant cells. These so-called persister cells endure otherwise lethal stress situations and enable restoration of bacterial populations upon return to favorable conditions. Persisters are especially notorious for their ability to survive antibiotic treatments without conventional resistance genes and to cause infection relapse. The persister state is typically correlated with reduction or inhibition of cellular activity. Early on, chromosomal toxin-antitoxin (TA) systems were suspected to induce the persister state in response to environmental stress. However, this idea has been challenged during the last years. Especially the involvement of toxins from type II TA systems in persister formation is put into question. For toxins from type I TA systems the debate has just started. Here, we would like to summarize recent knowledge gained for the type I TA system tisB/istR-1 from Escherichia coli. TisB is a small, membrane-targeting toxin, which disrupts the proton motive force (PMF), leading to membrane depolarization. Based on experimental data, we hypothesize that TisB primarily stabilizes the persister state through depolarization and further, secondary effects. We will present a simple model that will provide a framework for future directions.

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Section: Introductionmentioning

confidence: 99%

“…Different TA system types have been described over the years, and we would like to refer the reader to recent reviews on TA system biology ( Srivastava et al, 2021 ; Jurėnas et al, 2022 ). For the scope of this Perspective , we would like to focus on type I TA systems.…”

Section: Introductionmentioning

confidence: 99%

A Shift in Perspective: A Role for the Type I Toxin TisB as Persistence-Stabilizing Factor

Edelmann

Berghoff

2022

Front. Microbiol.

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“…There are currently eight types of TAS described in bacteria. The classification depends on the nature of the antitoxin (RNA in types I, III, and VIII, or small protein in the other TAS types), and the toxin (small protein in all but type VIII where the toxin is a small RNA), and how the antitoxin neutralizes the toxin activity (Song & Wood, 2020, Singh et al ., 2021, Srivastava et al ., 2021).…”

Section: Introductionmentioning

confidence: 99%

eDNA-stimulated cell dispersion fromCaulobacter crescentusbiofilms upon oxygen limitation is dependent on a toxin-antitoxin system

Berne

Zappa

Brun

2022

Preprint

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In their natural environment, most bacteria preferentially live as complex surface-attached multicellular colonies called biofilms. Biofilms begin with a few cells adhering to a surface, where they multiply to form a mature colony. When conditions deteriorate, cells can leave the biofilm. This dispersion is thought to be an important process that modifies the overall biofilm architecture and that promotes colonization of new environments. In Caulobacter crescentus biofilms, extracellular DNA (eDNA) is released upon cell death and prevents newborn cells from joining the established biofilm. Thus, eDNA promotes the dispersal of newborn cells and the subsequent colonization of new environments. These observations suggest that eDNA is a cue for sensing detrimental environmental conditions in the biofilm. Here we show that the toxin-antitoxin ParDE4 stimulates cell death in areas of a biofilm with decreased O2 availability. In conditions where O2 availability is low, eDNA concentration is correlated with cell death. Cell dispersal away from biofilms is decreased when parDE4 is deleted, probably due to the lower local eDNA concentration. Expression of parDE4 is positively regulated by O2 and the expression of this operon is decreased in biofilms where O2 availability is low. Thus, PCD by an O2-regulated toxin-antitoxin system stimulates dispersal away from areas of a biofilm with decreased O2 availability and favors colonization of a new, more hospitable environment.

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“…Adicionalmente, muitas toxinas do sistema TA atuam de forma semelhante a alguns antibióticos (Tabela 2), apresentando atividade bactericida ou bacteriostática (WEN; BEHIELS; DEVREESE, 2014). Nesse sentido, algumas estratégias podem ser utilizadas para o desenvolvimento de novas drogas baseadas em sistema TA, como: (1) impedir a formação do complexo TA, (2) ativação das proteases endógenas, (3) inibir a transcrição ou tradução do sistema TA, (4) desenvolvimento de droga baseada na toxina e (5) bacteriófagos capazes de introduzir toxinas no interior celular(BRAVO et al., 2018;SRIVASTAVA et al, 2021;RÓWNICKI et al, 2020). Além de atuar como antimicrobianos, o sistema TA possuem potencial antiviral e anticancerígeno.…”

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“…A atividade anticancerígena foi atribuída a capacidade de algumas toxinas como MazF e Kid de induzir apoptose em células eucarióticas. Aplicações biotecnológicas, como marca de seleção e manutenção genética, produção de proteínas, e morte direcionada de bactérias patogênicas na microbiota também são algumas das aplicabilidades do sistema TA(SRIVASTAVA et al, 2021).…”

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Análise do sistema toxina-antitoxina HipA/B na indução da persistência bacteriana de cepas de >i<Escherichia coli>/i< extraintestinal

Mitsunari¹,

Piazza²

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Palavras-chave: Sistemas toxina-antitoxina, Escherichia coli Extra intestinal Patogênicas, Persistência bacteriana, HipAB Os sistemas toxina-antitoxinas (TA) compreendem um conjunto de genes que são amplamente difundidos em procariotos. No cromossomo, os sistemas podem estar envolvidos na indução de morte celular em resposta a condições estressantes, indução de persistência, formação de biofilme, colonização de novos nichos, manutenção da mobilidade bacteriana e virulência de bactérias patogênicas. Em E. coli K12, 36 sistemas TA foram descritos, dos quais o do tipo II é o mais abundante e estudado. Dentre as oito toxinas pesquisadas nesse trabalho, o gene da toxina HipA está presente em 76 das 100 cepas de ExPEC estudadas. Apesar da abundância de hipA em ExPEC e em diversos genomas bacterianos, a participação dos sistemas hipA/B na indução da persistência ainda não é clara. Portanto, o sistema hipA/B de duas cepas ExPEC isoladas de infecção sanguínea foi deletado, e estas foram avaliadas quando a indução da persistência bacteriana na presença de antibióticos, formação de biofilme, resistência ao soro e sobrevivência em macrófagos. O sistema TA hipA/B não influenciou no fenótipo de resistência ao soro humano e na sobrevivência intracelular em macrófagos, no entanto, participou da indução da persistência por ciprofloxacino em um isolado (EC182); e da formação de biofilme em superfície de vidro do isolado (EC273).

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Toxin-antitoxin systems and their medical applications: current status and future perspective

Cited by 28 publications

References 166 publications

A Shift in Perspective: A Role for the Type I Toxin TisB as Persistence-Stabilizing Factor

A Shift in Perspective: A Role for the Type I Toxin TisB as Persistence-Stabilizing Factor

eDNA-stimulated cell dispersion fromCaulobacter crescentusbiofilms upon oxygen limitation is dependent on a toxin-antitoxin system

Análise do sistema toxina-antitoxina HipA/B na indução da persistência bacteriana de cepas de >i<Escherichia coli>/i< extraintestinal

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