Interactions between the toxin Kid of the bacterial <i>parD</i> system and the antitoxins Kis and MazE

Kamphuis, Monique B.; Monti, Maria Chiara; Heuvel, Robert H. H. van den; Santos-Sierra, Sandra; Folkers, Gert E.; Lemonnier, Marguerite; Dı́az-Orejas, Ramón; Heck, Albert J. R.; Boelens, Rolf

doi:10.1002/prot.21254

Cited by 29 publications

(46 citation statements)

References 51 publications

(78 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is perhaps not surprising given the specificity of other endoribonuclease systems, such as the kid and kis system of the parD operon of E. coli, as well as the sequence specificity of MazF (25,60). Indeed, at least two of the MazF homologs of M. tuberculosis have been shown to have slightly different RNA consensus cleavage sites (62).…”

Section: Vol 192 2010mentioning

confidence: 99%

“…These modules are generally expressed from a bicistronic operon wherein the upstream gene encodes an unstable antitoxin and the downstream gene encodes a stable toxin (18,22). The antitoxins neutralize their cognate toxins by forming tight protein-protein complexes that abrogate toxicity if both modules are present in equal concentrations (25). The two proteins have differing stabilities, however, so that in the absence of continued expression, the unstable antitoxin is eventually degraded, leading to growth arrest by the toxin (8).…”

mentioning

confidence: 99%

See 1 more Smart Citation

The Three RelE Homologs of Mycobacterium tuberculosis Have Individual, Drug-Specific Effects on Bacterial Antibiotic Tolerance

2010

View full text Add to dashboard Cite

In Escherichia coli, expression of the RelE and HipA toxins in the absence of their cognate antitoxins has been associated with generating multidrug-tolerant "persisters." Here we show that unlike persisters of E. coli, persisters of Mycobacterium tuberculosis selected with one drug do not acquire cross-resistance to other classes of drugs. M. tuberculosis has three homologs of RelE arranged in operons with their apparent antitoxins. Each toxin individually arrests growth of both M. tuberculosis and E. coli, an effect that is neutralized by coexpression of the cognate antitoxin. Overexpression or deletion of each of the RelE toxins had a toxin-and drug-specific effect on the proportion of bacilli surviving antibiotic killing. All three toxins were upregulated in vivo, but none of the deletions affected survival during murine infection. RelE2 overexpression increased bacterial survival rates in the presence of rifampin in vitro, while deletion significantly decreased survival rates. Strikingly, deletion of this toxin had no discernible effect on the level of persisters seen in rifampin-treated mice. Our results suggest that, in vivo, RelE-generated persisters are unlikely to play a significant role in the generation of bacilli that survive in the face of multidrug therapy or in the generation of multidrug-resistant M. tuberculosis.

show abstract

Section: Vol 192 2010mentioning

confidence: 99%

mentioning

confidence: 99%

The Three RelE Homologs of Mycobacterium tuberculosis Have Individual, Drug-Specific Effects on Bacterial Antibiotic Tolerance

2010

View full text Add to dashboard Cite

show abstract

“…A number of other toxinantitoxin pairs (e.g. CcdAB, Kis-Kid and Phd-Doc) have also been shown to form larger aggregates under certain conditions, but in these cases nonglobular chains of variable length consisting of alternating toxin and antitoxin molecules were identified (Dao-Thi et al, 2002;Kamphuis et al, 2007;Garcia-Pino et al, 2010). These extended structures have recently been interpreted in terms of a specific mechanism of transcription regulation called 'conditional cooperativity' (De Jonge et al, 2009;Garcia-Pino et al, 2010).…”

Section: Resultsmentioning

confidence: 99%

The ParE2–PaaA2 toxin–antitoxin complex fromEscherichia coliO157 forms a heterodocecamer in solution and in the crystal

et al. 2012

View full text Add to dashboard Cite

Escherichia coli O157 paaR2-paaA2-parE2 constitutes a unique threecomponent toxin-antitoxin (TA) module encoding a toxin (ParE2) related to the classic parDE family but with an unrelated antitoxin called PaaA2. The complex between PaaA2 and ParE2 was purified and characterized by analytical gel filtration, dynamic light scattering and small-angle X-ray scattering. It consists of a particle with a radius of gyration of 3.95 nm and is likely to form a heterododecamer. Crystals of the ParE2-PaaA2 complex diffract to 3.8 Å resolution and belong to space group P3 1 21 or P3 2 21, with unit-cell parameters a = b = 142.9, c = 87.5 Å . The asymmetric unit is consistent with a particle of around 125 kDa, which is compatible with the solution data. Therefore, the ParE2-PaaA2 complex is the largest toxin-antitoxin complex identified to date and its quaternary arrangement is likely to be of biological significance.

show abstract

“…This finding agrees with the 2:2 stoichiometry observed for the E. coli YefM-YoeB complex based on size exclusion chromatography of approximately 0.2 mg/ml of the YefM-YoeB-His complex, although 2:1 and 2:4 stoichiometries were also observed, but with fewer occurrences (I. Cherny and E. Gazit, unpublished). In the case of the Kis-Kid proteins, 1:2, 2:2, and 2:1 stoichiometries were also found, although the results depended on the relative protein concentrations (27). Subsequent Western hybridization using an antiHis 6 antibody confirmed the identity of the protein.…”

Section: Analysis Of Yefmmentioning

confidence: 86%

TheyefM-yoeBToxin-Antitoxin Systems ofEscherichia coliandStreptococcus pneumoniae: Functional and Structural Correlation

et al. 2007

View full text Add to dashboard Cite

Toxin-antitoxin loci belonging to the yefM-yoeB family are located in the chromosome or in some plasmids of several bacteria. We cloned the yefM-yoeB locus of Streptococcus pneumoniae, and these genes encode bona fide antitoxin (YefM Spn ) and toxin (YoeB Spn ) products. We showed that overproduction of YoeB Spn is toxic to Escherichia coli cells, leading to severe inhibition of cell growth and to a reduction in cell viability; this toxicity was more pronounced in an E. coli B strain than in two E. coli K-12 strains. The YoeB Spn -mediated toxicity could be reversed by the cognate antitoxin, YefM Spn , but not by overproduction of the E. coli YefM antitoxin. The pneumococcal proteins were purified and were shown to interact with each other both in vitro and in vivo. Far-UV circular dichroism analyses indicated that the pneumococcal antitoxin was partially, but not totally, unfolded and was different than its E. coli counterpart. Molecular modeling showed that the toxins belonging to the family were homologous, whereas the antitoxins appeared to be specifically designed for each bacterial locus; thus, the toxin-antitoxin interactions were adapted to the different bacterial environmental conditions. Both structural features, folding and the molecular modeled structure, could explain the lack of crosscomplementation between the pneumococcal and E. coli antitoxins.The gram-positive, spherical bacterium Streptococcus pneumoniae (pneumococcus) is the cause of many human diseases, such as pneumonia, bacterial blood poisoning (bacteremia), inflammation of the membranes surrounding the brain and spinal cord (meningitis), middle-ear infection (otitis media), osteomyelitis, septic arthritis, endocarditis, peritonitis, pericarditis, and sinusitis; pneumonia is the most severe disease (15,28). Although the pneumococcus can normally be found in the noses and throats of healthy individuals, it can grow and cause infection when the immune system is weakened. The people who are most at risk of developing pneumococcal pneumonia have a weakened immune system. These people include the elderly, infants, cancer patients, AIDS patients, postoperative patients, alcoholics, and people with diabetes. The global rate of mortality is more than 1,000,000 people per year, and this figure represents about 15 to 20% of the people infected.

show abstract

Interactions between the toxin Kid of the bacterial parD system and the antitoxins Kis and MazE

Abstract: The proteins Kid and Kis are the toxin and antitoxin, respectively, encoded by the parD operon of Escherichia coli plasmid R1. Kis prevents the inhibition of E.

Cited by 29 publications

References 51 publications

The Three RelE Homologs of Mycobacterium tuberculosis Have Individual, Drug-Specific Effects on Bacterial Antibiotic Tolerance

The Three RelE Homologs of Mycobacterium tuberculosis Have Individual, Drug-Specific Effects on Bacterial Antibiotic Tolerance

The ParE2–PaaA2 toxin–antitoxin complex fromEscherichia coliO157 forms a heterodocecamer in solution and in the crystal

TheyefM-yoeBToxin-Antitoxin Systems ofEscherichia coliandStreptococcus pneumoniae: Functional and Structural Correlation

Contact Info

Product

Resources

About