Type II Toxin-Antitoxin Loci, hipBA and Persisters

Lewis, Kim; Hansen, Sonja

doi:10.1007/978-3-642-33253-1_11

Cited by 2 publications

(3 citation statements)

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“…These results also propose a thermodynamic binding order, for the HipA protein, HipB dimer, and DNA molecule in a simulated physiological environment, that is, HipB dimer bind first to DNA to form HipB 2 + DNA complex; then HipA protein binding to HipB 2 + DNA complex to form HipA + HipB 2 + DNA or 2HipA + HipB 2 + DNA complex; finally, the remaining HipA proteins combining with the HipB dimer to form the HipA + HipB 2 or 2HipA + HipB 2 complex. In addition, the binding free energy of −24.82 kcal mol −1 calculated from the simulation of FHipB 2 + DNA model is similar to that of −26.56 kcal mol −1 calculated from the HipB 2 + DNA model, which supports the experimental result that these missing residues in the HipB subunit affect insignificantly the affinity of HipB for hipBA operator DNA (Hansen et al ., ; Lewis and Hansen, ).…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, the C‐terminal residues 75–88, which are near by the β1 sheet in the X‐ray densities of HipB protein, are missing (Schumacher et al ., ). Furtherly, Lewis and co‐workers reported that those missing residues affect insignificantly the affinity of HipB subunit for hipBA operator DNA or HipA protein (Hansen et al ., ; Lewis and Hansen, ). Moreover, the crystal structure of the 2HipA + HipB dimer complex was solved by applying the selected area (electron) diffraction technique (Evdokimov et al ., ).…”

Section: Introductionmentioning

confidence: 99%

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Interaction investigations of HipA binding to HipB dimer and HipB dimer + DNA complex: a molecular dynamics simulation study

Wang

et al. 2013

J of Molecular Recognition

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We carried out molecular dynamics simulations and free energy calculations for a series of ternary and diplex models for the HipA protein, HipB dimer, and DNA molecule to address the mechanism of HipA sequestration and the binding order of events from apo HipB/HipA to 2HipA + HipB dimer + DNA complex. The results revealed that the combination of DNA with the HipB dimer is energetically favorable for the combination of HipB dimer with HipA protein. The binding of DNA to HipB dimer induces a long-range allosteric communication from the HipB2 -DNA interface to the HipA-HipB2 interface, which involves the closeness of α1 helices of HipB dimer to HipA protein and formations of extra hydrogen bonds in the HipA-HipB2 interface through the extension of α2/3 helices in the HipB dimer. These simulated results suggested that the DNA molecule, as a regulative media, modulates the HipB dimer conformation, consequently increasing the interactions of HipB dimer with the HipA proteins, which explains the mechanism of HipA sequestration reported by the previous experiment. Simultaneously, these simulations also explored that the thermodynamic binding order in a simulated physiological environment, that is, the HipB dimer first bind to DNA to form HipB dimer + DNA complex, then capturing strongly the HipA proteins to form a ternary complex, 2HipA + HipB dimer + DNA, for sequestrating HipA in the nucleoid.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Interaction investigations of HipA binding to HipB dimer and HipB dimer + DNA complex: a molecular dynamics simulation study

Wang

et al. 2013

J of Molecular Recognition

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“…Therefore, certain stresses (Maisonneuve et al, 2013), or simply stochastic gene expression (Fasani & Savageau, 2013), can result in the toxin becoming active. Several different lines of evidence implicate type II TAs in persister formation (Lewis & Hansen, 2013;Schuster & Bertram, 2013;Holden, 2015). For example, the first mutant isolated with a higher persister fraction was an Escherichia coli which had a mutation in the HIPA toxin gene (Moyed & Bertrand, 1983).…”

Section: Introductionmentioning

confidence: 99%

Persistence and resistance as complementary bacterial adaptations to antibiotics

Vogwill

Comfort

Furió

et al. 2016

J of Evolutionary Biology

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Bacterial persistence represents a simple of phenotypic heterogeneity, whereby a proportion of cells in an isogenic bacterial population can survive exposure to lethal stresses such as antibiotics. In contrast, genetically based antibiotic resistance allows for continued growth in the presence of antibiotics. It is unclear, however, whether resistance and persistence are complementary or alternative evolutionary adaptations to antibiotics. Here, we investigate the co‐evolution of resistance and persistence across the genus Pseudomonas using comparative methods that correct for phylogenetic nonindependence. We find that strains of Pseudomonas vary extensively in both their intrinsic resistance to antibiotics (ciprofloxacin and rifampicin) and persistence following exposure to these antibiotics. Crucially, we find that persistence correlates positively to antibiotic resistance across strains. However, we find that different genes control resistance and persistence implying that they are independent traits. Specifically, we find that the number of type II toxin–antitoxin systems (TAs) in the genome of a strain is correlated to persistence, but not resistance. Our study shows that persistence and antibiotic resistance are complementary, but independent, evolutionary adaptations to stress and it highlights the key role played by TAs in the evolution of persistence.

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Type II Toxin-Antitoxin Loci, hipBA and Persisters

Cited by 2 publications

References 63 publications

Interaction investigations of HipA binding to HipB dimer and HipB dimer + DNA complex: a molecular dynamics simulation study

Interaction investigations of HipA binding to HipB dimer and HipB dimer + DNA complex: a molecular dynamics simulation study

Persistence and resistance as complementary bacterial adaptations to antibiotics

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