Pathogen DNA as target for host-generated oxidative stress: Role for repair of bacterial DNA damage in Helicobacter pylori colonization
Helicobacter pylori elicits an oxidative stress during host colonization. This oxidative stress is known to cause lesions in the host DNA. Here we addressed the question as to whether the pathogen DNA is subject to lethal or mutational damage by the host-generated oxidative response. H. pylori Hpnth...
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2003
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00278424_v100_n5_p2789_ORourke http://hdl.handle.net/20.500.12110/paper_00278424_v100_n5_p2789_ORourke |
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paper:paper_00278424_v100_n5_p2789_ORourke2023-06-08T14:54:19Z Pathogen DNA as target for host-generated oxidative stress: Role for repair of bacterial DNA damage in Helicobacter pylori colonization bacterial DNA endonuclease endonuclease iii oxidizing agent pyrimidine derivative unclassified drug adaptation animal cell animal experiment animal model article bacterial colonization bacterial genome bacterial infection bacterial mutation bacterial strain competitive ability controlled study DNA adduct DNA damage DNA repair enzyme activity enzyme deficiency Helicobacter pylori host pathogen interaction macrophage activation mouse mutation rate nonhuman open reading frame oxidative stress polymerase chain reaction priority journal sequence analysis stomach Animals Bacterial Proteins DNA DNA Damage DNA Repair Dose-Response Relationship, Drug Drug Resistance Genes, Bacterial Genetic Complementation Test Genotype Helicobacter pylori Hydrogen Peroxide Macrophages Mice Mutation Oxidative Stress Oxygen Phenotype Plasmids Rifampin Sensitivity and Specificity Stomach Vitamin K 3 Animalia Bacteria (microorganisms) Helicobacter pylori Helicobacter pylori elicits an oxidative stress during host colonization. This oxidative stress is known to cause lesions in the host DNA. Here we addressed the question as to whether the pathogen DNA is subject to lethal or mutational damage by the host-generated oxidative response. H. pylori Hpnth mutants unable to repair oxidized pyrimidines from the bacterial DNA were generated. H. pylori strains lacking a functional endonuclease III (HpNth) showed elevated spontaneous and induced mutation rates and were more sensitive than the parental strain to killing by exposure to oxidative agents or activated macrophages. Although under laboratory conditions the Hpnth mutant strain grows as well as the wild-type strain, in a mouse infection the stomach bacterial load gradually decreases while the population in the wild-type strain remains stable, showing that endonuclease III deficiency reduces the colonization capacity of the pathogen. In coinfection experiments with a wild-type strain, Hpnth cells are eradicated 15 days postinfection (p.i.) even when inoculated in a 1:9 wild-type:mutant strain ratio, revealing mutagenic lesions that are counterselected under competition conditions. These results show that the host effectively induces lethal and premutagenic oxidative DNA adducts on the H. pylori genome. The possible consequences of these DNA lesions on the adaptability of H. pylori strains to new hosts are discussed. 2003 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00278424_v100_n5_p2789_ORourke http://hdl.handle.net/20.500.12110/paper_00278424_v100_n5_p2789_ORourke |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
bacterial DNA endonuclease endonuclease iii oxidizing agent pyrimidine derivative unclassified drug adaptation animal cell animal experiment animal model article bacterial colonization bacterial genome bacterial infection bacterial mutation bacterial strain competitive ability controlled study DNA adduct DNA damage DNA repair enzyme activity enzyme deficiency Helicobacter pylori host pathogen interaction macrophage activation mouse mutation rate nonhuman open reading frame oxidative stress polymerase chain reaction priority journal sequence analysis stomach Animals Bacterial Proteins DNA DNA Damage DNA Repair Dose-Response Relationship, Drug Drug Resistance Genes, Bacterial Genetic Complementation Test Genotype Helicobacter pylori Hydrogen Peroxide Macrophages Mice Mutation Oxidative Stress Oxygen Phenotype Plasmids Rifampin Sensitivity and Specificity Stomach Vitamin K 3 Animalia Bacteria (microorganisms) Helicobacter pylori |
| spellingShingle |
bacterial DNA endonuclease endonuclease iii oxidizing agent pyrimidine derivative unclassified drug adaptation animal cell animal experiment animal model article bacterial colonization bacterial genome bacterial infection bacterial mutation bacterial strain competitive ability controlled study DNA adduct DNA damage DNA repair enzyme activity enzyme deficiency Helicobacter pylori host pathogen interaction macrophage activation mouse mutation rate nonhuman open reading frame oxidative stress polymerase chain reaction priority journal sequence analysis stomach Animals Bacterial Proteins DNA DNA Damage DNA Repair Dose-Response Relationship, Drug Drug Resistance Genes, Bacterial Genetic Complementation Test Genotype Helicobacter pylori Hydrogen Peroxide Macrophages Mice Mutation Oxidative Stress Oxygen Phenotype Plasmids Rifampin Sensitivity and Specificity Stomach Vitamin K 3 Animalia Bacteria (microorganisms) Helicobacter pylori Pathogen DNA as target for host-generated oxidative stress: Role for repair of bacterial DNA damage in Helicobacter pylori colonization |
| topic_facet |
bacterial DNA endonuclease endonuclease iii oxidizing agent pyrimidine derivative unclassified drug adaptation animal cell animal experiment animal model article bacterial colonization bacterial genome bacterial infection bacterial mutation bacterial strain competitive ability controlled study DNA adduct DNA damage DNA repair enzyme activity enzyme deficiency Helicobacter pylori host pathogen interaction macrophage activation mouse mutation rate nonhuman open reading frame oxidative stress polymerase chain reaction priority journal sequence analysis stomach Animals Bacterial Proteins DNA DNA Damage DNA Repair Dose-Response Relationship, Drug Drug Resistance Genes, Bacterial Genetic Complementation Test Genotype Helicobacter pylori Hydrogen Peroxide Macrophages Mice Mutation Oxidative Stress Oxygen Phenotype Plasmids Rifampin Sensitivity and Specificity Stomach Vitamin K 3 Animalia Bacteria (microorganisms) Helicobacter pylori |
| description |
Helicobacter pylori elicits an oxidative stress during host colonization. This oxidative stress is known to cause lesions in the host DNA. Here we addressed the question as to whether the pathogen DNA is subject to lethal or mutational damage by the host-generated oxidative response. H. pylori Hpnth mutants unable to repair oxidized pyrimidines from the bacterial DNA were generated. H. pylori strains lacking a functional endonuclease III (HpNth) showed elevated spontaneous and induced mutation rates and were more sensitive than the parental strain to killing by exposure to oxidative agents or activated macrophages. Although under laboratory conditions the Hpnth mutant strain grows as well as the wild-type strain, in a mouse infection the stomach bacterial load gradually decreases while the population in the wild-type strain remains stable, showing that endonuclease III deficiency reduces the colonization capacity of the pathogen. In coinfection experiments with a wild-type strain, Hpnth cells are eradicated 15 days postinfection (p.i.) even when inoculated in a 1:9 wild-type:mutant strain ratio, revealing mutagenic lesions that are counterselected under competition conditions. These results show that the host effectively induces lethal and premutagenic oxidative DNA adducts on the H. pylori genome. The possible consequences of these DNA lesions on the adaptability of H. pylori strains to new hosts are discussed. |
| title |
Pathogen DNA as target for host-generated oxidative stress: Role for repair of bacterial DNA damage in Helicobacter pylori colonization |
| title_short |
Pathogen DNA as target for host-generated oxidative stress: Role for repair of bacterial DNA damage in Helicobacter pylori colonization |
| title_full |
Pathogen DNA as target for host-generated oxidative stress: Role for repair of bacterial DNA damage in Helicobacter pylori colonization |
| title_fullStr |
Pathogen DNA as target for host-generated oxidative stress: Role for repair of bacterial DNA damage in Helicobacter pylori colonization |
| title_full_unstemmed |
Pathogen DNA as target for host-generated oxidative stress: Role for repair of bacterial DNA damage in Helicobacter pylori colonization |
| title_sort |
pathogen dna as target for host-generated oxidative stress: role for repair of bacterial dna damage in helicobacter pylori colonization |
| publishDate |
2003 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00278424_v100_n5_p2789_ORourke http://hdl.handle.net/20.500.12110/paper_00278424_v100_n5_p2789_ORourke |
| _version_ |
1768544492764266496 |