Two <i>higBA</i> loci in the <i>Vibrio cholerae</i> superintegron encode mRNA cleaving enzymes and can stabilize plasmids

Christensen-Dalsgaard, Mikkel; Gerdes, Kenn

doi:10.1111/j.1365-2958.2006.05385.x

Cited by 165 publications

(159 citation statements)

References 69 publications

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“…The first indication that the mRNases might be involved in persistence came from the observation that their ectopic overproduction not only very efficiently inhibited translation (consistent with mRNA cleavage) but induced dormancy from which the cells could be rapidly resuscitated by the induction of cognate antitoxin genes (21,30,31). Cells overproducing TA-encoded mRNases were, similar to persister cells, tolerant to antibiotics (32)(33)(34)(35).…”

mentioning

confidence: 99%

RETRACTED: Bacterial persistence by RNA endonucleases

Maisonneuve

Shakespeare

Jørgensen

et al. 2011

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

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459

557

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Bacteria form persisters, individual cells that are highly tolerant to different types of antibiotics. Persister cells are genetically identical to nontolerant kin but have entered a dormant state in which they are recalcitrant to the killing activity of the antibiotics. The molecular mechanisms underlying bacterial persistence are unknown. Here, we show that the ubiquitous Lon (Long Form Filament) protease and mRNA endonucleases (mRNases) encoded by toxin-antitoxin (TA) loci are required for persistence in Escherichia coli . Successive deletion of the 10 mRNase-encoding TA loci of E . coli progressively reduced the level of persisters, showing that persistence is a phenotype common to TA loci. In all cases tested, the antitoxins, which control the activities of the mRNases, are Lon substrates. Consistently, cells lacking lon generated a highly reduced level of persisters. Moreover, Lon overproduction dramatically increased the levels of persisters in wild-type cells but not in cells lacking the 10 mRNases. These results support a simple model according to which mRNases encoded by TA loci are activated in a small fraction of growing cells by Lon-mediated degradation of the antitoxins. Activation of the mRNases, in turn, inhibits global cellular translation, and thereby induces dormancy and persistence. Many pathogenic bacteria known to enter dormant states have a plethora of TA genes. Therefore, in the future, the discoveries described here may lead to a mechanistic understanding of the persistence phenomenon in pathogenic bacteria.

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confidence: 99%

RETRACTED: Bacterial persistence by RNA endonucleases

Maisonneuve

Shakespeare

Jørgensen

et al. 2011

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

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459

557

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“…8). This result was in striking contrast to all other TA toxins-MazF, PemK, ChpBK, RelE, and HigB-known to target and rapidly degrade mRNA (27,28,30,31). Therefore, we suspected that the presence of Doc might stabilize mRNA.…”

Section: Phd Can Rescue Doc-mediated In Vitro Translation Arrest and mentioning

confidence: 66%

Bacterial addiction module toxin Doc inhibits translation elongation through its association with the 30S ribosomal subunit

Liu¹,

Zhang²,

Inouye³

et al. 2008

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

119

103

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Bacterial toxin-antitoxin (TA) systems (or ''addiction modules'') typically facilitate cell survival during intervals of stress by inducing a state of reversible growth arrest. However, upon prolonged stress, TA toxin action leads to cell death. TA systems have also been implicated in several clinically important phenomena: biofilm formation, bacterial persistence during antibiotic treatment, and bacterial pathogenesis. TA systems harbored by pathogens also serve as attractive antibiotic targets. To date, the mechanism of action of the majority of known TA toxins has not yet been elucidated. We determined the mode of action of the Doc toxin of the Phd-Doc TA system. Doc expression resulted in rapid cell growth arrest and marked inhibition of translation without significant perturbation of transcription or replication. However, Doc did not cleave mRNA as do other addiction-module toxins whose activities result in translation inhibition. Instead, Doc induction mimicked the effects of treatment with the aminoglycoside antibiotic hygromycin B (HygB): Both Doc and HygB interacted with 30S ribosomal subunits, stabilized polysomes, and resulted in a significant increase in mRNA half-life. HygB also competed with ribosome-bound Doc, whereas HygB-resistant mutants suppressed Doc toxicity, suggesting that the Doc-binding site includes that of HygB (i.e., helix 44 region of 16S rRNA containing the A, P, and E sites). Overall, our results illuminate an intracellular target and mechanism of TA toxin action drawn from aminoglycoside antibiotics: Doc toxicity is the result of inhibition of translation elongation, possibly at the translocation step, through its interaction with the 30S ribosomal subunit.antitoxin ͉ hygromycin B ͉ bacteriophage P1 ͉ 16S rRNA ͉ postsegregational killing

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“…Of these, the mazEF, relBE, and vapBC families have been studied in detail. All three of these toxins cleave mRNA; RelE requires the ribosome for RNA cleavage, whereas MazF, HigB, and VapC do not (7)(8)(9)(10). The CcdB and ParE toxins inhibit chromosome replication through DNA gyrase (11)(12)(13); the Doc toxin inhibits the 30 S subunit of the ribosome (14), and HipA phosphorylates the translation factor EF-Tu (15).…”

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confidence: 99%

Toxin-Antitoxin Systems of Mycobacterium smegmatis Are Essential for Cell Survival

Frampton

Aggio

Villas‐Bôas

et al. 2012

Journal of Biological Chemistry

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Background: Mycobacteria harbor a vast array of toxin-antitoxin modules, but their roles remain largely unknown. Results: Deletion of all TA modules in Mycobacterium smegmatis caused a survival defect and alterations in amino acid metabolism. Conclusion:We demonstrate an essential role for TA modules in mycobacterial metabolism and survival. Significance: These results may explain the basis for 88 TA modules in M. tuberculosis where metabolism must be tightly controlled.

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Two higBA loci in the Vibrio cholerae superintegron encode mRNA cleaving enzymes and can stabilize plasmids

Cited by 165 publications

References 69 publications

RETRACTED: Bacterial persistence by RNA endonucleases

RETRACTED: Bacterial persistence by RNA endonucleases

Bacterial addiction module toxin Doc inhibits translation elongation through its association with the 30S ribosomal subunit

Toxin-Antitoxin Systems of Mycobacterium smegmatis Are Essential for Cell Survival

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