Toxin–Antitoxin Systems in Pathogenic Bacteria

Alonso, Juan C.

doi:10.3390/toxins13020074

Cited by 7 publications

(6 citation statements)

References 16 publications

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“…Because of their association with virulence in bacterial pathogens, TA systems have been recognized as promising therapeutic targets. , We found that the antitoxin HigA can repress the exsA and amrZ promoters to reduce the expression of T3SS and T6SS, respectively, both of which are responsible for virulence of P. aeruginosa.…”

Section: Discussionmentioning

confidence: 97%

“…Antitoxins are typically susceptible to cellular protease degradation under various stresses; this increases the toxin/antitoxin ratio and causes growth inhibition. Emerging evidence has shown that the type II TA systems are involved in pathogen adaptation to host tissues and chronic or recurrent infections. − For instance, Agarwal et al reported that the VapBC type II TA systems from Mycobacterium tuberculosis is a key pathogenesis regulator; the authors demonstrated that the toxin VapB inhibits the expression of virulence-associated proteins and that the cellular VapB/VapC ratio is crucial for M. tuberculosis to adapt to host environments .…”

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confidence: 99%

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Type II Antitoxin HigA Is a Key Virulence Regulator in Pseudomonas aeruginosa

et al. 2021

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Bacterial type II toxin-antitoxin (TA) systems are abundant genetic elements and are involved in a diverse array of physiological processes. These systems encode an antitoxin protein that directly binds and effectively neutralizes the protein toxin. Recent studies have highlighted the key roles of type II TA modules in bacterial virulence and pathogenesis, but the underlying mechanisms remain unclear. Here, we investigated the antitoxin HigA in Pseudomonas aeruginosa infection. Proteomic analysis of the higA deletion strain revealed an enhanced expression of pathogenic proteins. We further verified that HigA negatively controlled T3SS and T6SS expression by directly interacting with the promoter regions of the regulators amrZ and exsA, respectively. In other words, the reversal of HigA-mediated transcriptional inhibition on stress stimulation could induce virulence genes. These findings confirm the crucial roles of the type II antitoxin in bacterial infection, which highlights the potential of the HigBA TA system as an antibacterial treatment target.

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Section: Discussionmentioning

confidence: 97%

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confidence: 99%

Type II Antitoxin HigA Is a Key Virulence Regulator in Pseudomonas aeruginosa

et al. 2021

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“…These have been implicated to help bacteria adapt to different stress conditions by downregulating metabolism and potentiating transition into dormant like stage ( Unterholzner et al, 2013 ; Chan et al, 2016 ). In addition to slowing down of bacterial metabolism, TA systems are also shown to be essential for persistence and bacterial pathogenesis ( Wen et al, 2014 ; Yang and Walsh, 2017 ; Alonso, 2021 ). The large number of TA systems in the genome of M. tuberculosis makes it difficult to perceive the involvement of individual TA systems in the pathogen biology.…”

Section: Discussionmentioning

confidence: 99%

HigB1 Toxin in Mycobacterium tuberculosis Is Upregulated During Stress and Required to Establish Infection in Guinea Pigs

et al. 2021

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The extraordinary expansion of Toxin Antitoxin (TA) modules in the genome of Mycobacterium tuberculosis has received significant attention over the last few decades. The cumulative evidence suggests that TA systems are activated in response to stress conditions and are essential for M. tuberculosis pathogenesis. In M. tuberculosis, Rv1955-Rv1956-Rv1957 constitutes the only tripartite TAC (Toxin Antitoxin Chaperone) module. In this locus, Rv1955 (HigB1) encodes for the toxin and Rv1956 (HigA1) encodes for antitoxin. Rv1957 encodes for a SecB-like chaperone that regulates HigBA1 toxin antitoxin system by preventing HigA1 degradation. Here, we have investigated the physiological role of HigB1 toxin in stress adaptation and pathogenesis of Mycobacterium tuberculosis. qPCR studies revealed that higBA1 is upregulated in nutrient limiting conditions and upon exposure to levofloxacin. We also show that the promoter activity of higBA1 locus in M. tuberculosis is (p)ppGpp dependent. We observed that HigB1 locus is non-essential for M. tuberculosis growth under different stress conditions in vitro. However, guinea pigs infected with higB1 deletion strain exhibited significantly reduced bacterial loads and pathological damage in comparison to the animals infected with the parental strain. Transcriptome analysis suggested that deletion of higB1 reduced the expression of genes involved in virulence, detoxification and adaptation. The present study describes the role of higB1 toxin in M. tuberculosis physiology and highlights the importance of higBA1 locus during infection in host tissues.

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“…Other mechanisms of plasmid maintenance include the production of toxin-antitoxin (TA) systems. Toxin-antitoxin systems are important for plasmid maintenance; toxins produced by plasmids kill cells that have lost plasmids during cell division, thus selecting for plasmid-carrying cells ( 17 ). Plasmid pSBP2_mcr4 encodes three different type II TA systems of the RelE/ParE type, Phd/YefM family, and HiCAB type.…”

Section: Observationmentioning

confidence: 99%

Novel Plasmid Carrying Mobile Colistin Resistance Gene mcr-4.3 and Mercury Resistance Genes in Shewanella baltica: Insights into Mobilization of mcr-4.3 in Shewanella Species

et al. 2022

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We identified two new plasmids in Shewanella baltica isolated from wild Atlantic mackerel ( Scomber scombrus ) collected from the northern North Sea, one plasmid carrying the mcr-4.3 gene for colistin resistance and the operon merRPAT for mercury resistance and the other carrying multiple heavy metal resistance genes. The marine environment has been recognized as a source of new resistance genes that are found in human pathogens.

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Toxin–Antitoxin Systems in Pathogenic Bacteria

Abstract: Toxin–antitoxin (TA) systems, which are ubiquitously present in plasmids, bacterial and archaeal genomes, are classified as types I to VI, according to the nature of the antitoxin and to the mode of toxin inhibition [...]

Cited by 7 publications

References 16 publications

Type II Antitoxin HigA Is a Key Virulence Regulator in Pseudomonas aeruginosa

Type II Antitoxin HigA Is a Key Virulence Regulator in Pseudomonas aeruginosa

HigB1 Toxin in Mycobacterium tuberculosis Is Upregulated During Stress and Required to Establish Infection in Guinea Pigs

Novel Plasmid Carrying Mobile Colistin Resistance Gene mcr-4.3 and Mercury Resistance Genes in Shewanella baltica: Insights into Mobilization of mcr-4.3 in Shewanella Species

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