4.5 Review

Toxin-antitoxin systems in bacterial pathogenesis

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Review Microbiology

Biology and evolution of bacterial toxin-antitoxin systems

Dukas Jurenas et al.

Summary: Toxin-antitoxin systems, composed of toxins and antitoxins, are widely found in bacterial genomes. Recent studies have challenged the traditional understanding of these systems and focused more on their role in host-genetic element interactions.

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The role of PemIK (PemK/PemI) type II TA system from Klebsiella pneumoniae clinical strains in lytic phage infection

Ines Bleriot et al.

Summary: This study demonstrates the important role of the PemK/PemI TA system in phage inhibition. Overexpression of the PemK toxin leads to dormancy of bacteria, resulting in inhibition of phage infections.

SCIENTIFIC REPORTS (2022)

Article Microbiology

Disruption of MenT2 toxin impairs the growth of Mycobacterium tuberculosis in guinea pigs

Tannu Priya Gosain et al.

Summary: This article investigates the role of MenT2 in mycobacterial physiology and disease pathogenesis. It is found that MenT2 plays an important role in the establishment of disease in guinea pigs and in the resistance to nitrosative stress in M. tuberculosis. The transcript levels of menT2 and menA2 are increased under nitrosative stress, and the Delta menT2 mutant strain shows increased resistance to nitrosative stress.

MICROBIOLOGY-SGM (2022)

Article Microbiology

The DarTG toxin-antitoxin system provides phage defence by ADP-ribosylating viral DNA

Michele LeRoux et al.

Summary: The DarTG toxin-antitoxin system protects bacteria against phage infection by ADP-ribosylating viral DNA. The system can be evaded by phages through mutation of their DNA polymerase or the gp61.2 anti-DarT factor. A bioinformatics search identified homologues of DarTG, a family of TA systems that provide strong protection against phages. The toxin of DarTG modifies viral DNA upon phage infection, preventing replication and virion production. Phages have evolved mutations to overcome DarTG defense. These findings suggest that phage defense may be a common function of TA systems.

NATURE MICROBIOLOGY (2022)

Article Microbiology

A functional selection reveals previously undetected anti-phage defence systems in the E. coli pangenome

Christopher N. Vassallo et al.

Summary: The study identified numerous new candidate defense systems in E. coli using an experimental selection scheme, demonstrating that intact prophages and mobile genetic elements are primary reservoirs and distributors of defense systems.

NATURE MICROBIOLOGY (2022)

Article Biochemistry & Molecular Biology

Structural Basis for Toxin Inhibition in the VapXD Toxin-Antitoxin System

Marie B. Bertelsen et al.

Summary: The study presents the structure of the intact H. influenzae VapXD complex, showing an unusual 2:1 TA molecular stoichiometry. The VapX antitoxin consists of a domain that can dock into a cavity on the toxin dimer, while the VapD toxin can adapt to interacting with an asymmetrical antitoxin.

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

Arun Sharma et al.

Summary: The expansion of Toxin Antitoxin modules in Mycobacterium tuberculosis has been extensively studied, highlighting their importance in stress response and pathogenesis. Specifically, the HigB1 toxin plays a crucial role in stress adaptation and pathogenesis of M. tuberculosis, as well as in regulating the expression of virulence-related genes. Deletion of higB1 results in reduced bacterial loads and pathological damage in infected guinea pigs, emphasizing the significance of the higBA1 locus during infection in host tissues.

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Toxin-antitoxin RNA pairs safeguard CRISPR-Cas systems

Ming Li et al.

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

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Michele LeRoux et al.

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Chromosomal toxin-antitoxin systems in Pseudomonas putida are rather selfish than beneficial

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An ADP-ribosyltransferase Alt of bacteriophage T4 negatively regulates the Escherichia coli MazF toxin of a toxin-antitoxin module

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The Toxin-Antitoxin System DarTG Catalyzes Reversible ADP-Ribosylation of DNA

Gytis Jankevicius et al.

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VapCs of Mycobacterium tuberculosis cleave RNAs essential for translationl

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tRNA is a new target for cleavage by a MazF toxin

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Toxin-Antitoxin Modules Are Pliable Switches Activated by Multiple Protease Pathways

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The MqsR/MqsA toxin/antitoxin system protects Escherichia coli during bile acid stress

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Vasili Hauryliuk et al.

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Stochastic induction of persister cells by HipA through (p)ppGpp-mediated activation of mRNA endonucleases

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MazF ribonucleases promote Mycobacterium tuberculosis drug tolerance and virulence in guinea pigs

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Distinct type I and type II toxin-antitoxin modules control Salmonella lifestyle inside eukaryotic cells

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Identification and characterization of a HEPN-MNT family type II toxin-antitoxin in Shewanella oneidensis

Jianyun Yao et al.

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Structure of the Proteus vulgaris HigB-(HigA)2-HigB Toxin-Antitoxin Complex

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MazF-induced Growth Inhibition and Persister Generation in Escherichia coli

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The ZorO-OrzO type I toxin-antitoxin locus: repression by the OrzO antitoxin

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RalR (a DNase) and RalA (a small RNA) form a type I toxin-antitoxin system in Escherichia coli

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Multiple Toxin-Antitoxin Systems in Mycobacterium tuberculosis

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A Bacterial Toxin Inhibits DNA Replication Elongation through a Direct Interaction with the β Sliding Clamp

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Structure and activity of AbiQ, a lactococcal endoribonuclease belonging to the type III toxinantitoxin system

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The Fic protein Doc uses an inverted substrate to phosphorylate and inactivate EF-Tu

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β-lactam antibiotics promote bacterial mutagenesis via an RpoS-mediated reduction in replication fidelity

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HipA-mediated antibiotic persistence via phosphorylation of the glutamyl-tRNA-synthetase

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Antitoxin MqsA Represses Curli Formation Through the Master Biofilm Regulator CsgD

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Single Transmembrane Peptide DinQ Modulates Membrane-Dependent Activities

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A new type V toxin-antitoxin system where mRNA for toxin GhoT is cleaved by antitoxin GhoS

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A conserved RpoS-dependent small RNA controls the synthesis of major porin OmpD

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Type I toxin-antitoxin systems in Bacillus subtilis

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Escherichia coli rnlA and rnlB Compose a Novel Toxin-Antitoxin System

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Crystal Structure of the VapBC Toxin-Antitoxin Complex from Shigella flexneri Reveals a Hetero-Octameric DNA-Binding Assembly

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RatA (YfjG), an Escherichia coli toxin, inhibits 70S ribosome association to block translation initiation

Yonglong Zhang et al.

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Antitoxin MqsA helps mediate the bacterial general stress response

Xiaoxue Wang et al.

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A processed noncoding RNA regulates an altruistic bacterial antiviral system

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SecB-like chaperone controls a toxin-antitoxin stress-responsive system in Mycobacterium tuberculosis

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Escherichia coli toxin/antitoxin pair MqsR/MqsA regulate toxin CspD

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