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O'Rourke, E.J.; Chevalier, C.; Pinto, A.V.; Thiberge, J.M.; Ielpi, L.; Labigne, A.; Radicella, J.P. "Pathogen DNA as target for host-generated oxidative stress: Role for repair of bacterial DNA damage in Helicobacter pylori colonization" (2003) Proceedings of the National Academy of Sciences of the United States of America. 100(5):2789-2794
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Abstract:

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.

Registro:

Documento: Artículo
Título:Pathogen DNA as target for host-generated oxidative stress: Role for repair of bacterial DNA damage in Helicobacter pylori colonization
Autor:O'Rourke, E.J.; Chevalier, C.; Pinto, A.V.; Thiberge, J.M.; Ielpi, L.; Labigne, A.; Radicella, J.P.
Filiación:Dept. de Radiobiol. et Radiopathol., Commsrt. a l'Energie Atomique (CEA), U. Mixte Rech. 217/Ctr. Natl. Rech., BP6, F-92265 Fontenay-aux-Roses, France
Instituto Leloir, Naturales-Universidad Buenos Aires, Consejo Nac. Invest. Cie./Tec. ARG, C1405 BWE Buenos Aires, Argentina
U. de Pathogenie Bact. des Muqueuses, Institut Pasteur, F-75724 Paris, France
Palabras clave: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
Año:2003
Volumen:100
Número:5
Página de inicio:2789
Página de fin:2794
DOI: http://dx.doi.org/10.1073/pnas.0337641100
Título revista:Proceedings of the National Academy of Sciences of the United States of America
Título revista abreviado:Proc. Natl. Acad. Sci. U. S. A.
ISSN:00278424
CODEN:PNASA
CAS:endonuclease, 9055-11-2; Bacterial Proteins; DNA, 9007-49-2; Hydrogen Peroxide, 7722-84-1; Oxygen, 7782-44-7; Rifampin, 13292-46-1; Vitamin K 3, 58-27-5
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00278424_v100_n5_p2789_ORourke

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Citas:

---------- APA ----------
O'Rourke, E.J., Chevalier, C., Pinto, A.V., Thiberge, J.M., Ielpi, L., Labigne, A. & Radicella, J.P. (2003) . Pathogen DNA as target for host-generated oxidative stress: Role for repair of bacterial DNA damage in Helicobacter pylori colonization. Proceedings of the National Academy of Sciences of the United States of America, 100(5), 2789-2794.
http://dx.doi.org/10.1073/pnas.0337641100
---------- CHICAGO ----------
O'Rourke, E.J., Chevalier, C., Pinto, A.V., Thiberge, J.M., Ielpi, L., Labigne, A., et al. "Pathogen DNA as target for host-generated oxidative stress: Role for repair of bacterial DNA damage in Helicobacter pylori colonization" . Proceedings of the National Academy of Sciences of the United States of America 100, no. 5 (2003) : 2789-2794.
http://dx.doi.org/10.1073/pnas.0337641100
---------- MLA ----------
O'Rourke, E.J., Chevalier, C., Pinto, A.V., Thiberge, J.M., Ielpi, L., Labigne, A., et al. "Pathogen DNA as target for host-generated oxidative stress: Role for repair of bacterial DNA damage in Helicobacter pylori colonization" . Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 5, 2003, pp. 2789-2794.
http://dx.doi.org/10.1073/pnas.0337641100
---------- VANCOUVER ----------
O'Rourke, E.J., Chevalier, C., Pinto, A.V., Thiberge, J.M., Ielpi, L., Labigne, A., et al. Pathogen DNA as target for host-generated oxidative stress: Role for repair of bacterial DNA damage in Helicobacter pylori colonization. Proc. Natl. Acad. Sci. U. S. A. 2003;100(5):2789-2794.
http://dx.doi.org/10.1073/pnas.0337641100