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Novel bacterial strategy to cope with host defenses uncovered

Helicobacter pylori has an unprecedented nitric oxide detoxifying system

Oeiras, 01.02.12

Pathologies like chronic gastritis and gastric ulcers are caused by a bacterium, Helicobacter pylori, able to bypass the immunity control systems and to sustain long term colonization inside the harsh environment of the stomach. Now, ITQB researchers from the Molecular Genetics of Microbial Resistance Lab and collaborators from the Institut Pasteur in Paris have identified a new protein in Helicobacter pylori, which assures the bacterial survival inside the host by protecting bacteria against the effects of nitric oxide. The work is published in the journal Antioxidants and Redox Signaling.

Many bacteria resort to nitric oxide (NO) detoxification systems to counteract the host NO production, a crucial tool of mammal’s innate immunity for the control and clearance of pathogens. The Gram negative bacteria H. pylori lack the typical bacterial systems, which suggested to researchers that other unknown proteins could be involved in NO detoxification. After screening a collection of mutants for unusual growth in the presence of NO, researchers identified a gene, unknown till then, that confers resistance to NO.

The next step was to gather clues about this new gene’s function, resorting to genetics, biochemistry and molecular biology. Clue number 1, the mutant H. pylori was more susceptible to nitric oxide than the wild type strains. Clue number 2, mutants were also less able to survive upon incubation with the immune system macrophages. Clue number 3, mutants were less efficient in colonizing the mice themselves. Clue number 4,if mice lacked the NO production mechanism, mutant bacteria were as efficient as wild type. Clue number 5, the purified wild type protein was an active NO reductase. Clue number 6, sequence analysis revealed that the new gene is present in several other prokaryotes. Conclusion, a previously hypothetical protein of H. pylory is now renamed NorH, for NO reductase of Helycobacter pylori, and represents a new family of enzymes for microbial protection against nitric oxide associated stress.

This study was jointly coordinated by Lígia Saraiva, head of the Molecular Genetics of Microbial Resistance Lab, and Ivo Boneca, ITQB alumnus now at the Institut Pasteur.

Original Article

Antioxidants & Redox Signaling, ahead of print. doi:10.1089/ars.2011.4304.

Helicobacter pylori has an unprecedented nitric oxide detoxifying system

Marta C. Justino1,2, Chantal Ecobichon2,3, André F. Fernandes1, Ivo G. Boneca2,3 and Lígia M. Saraiva1

1 - Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Oeiras, Portugal
2 - Institut Pasteur, Group Biology and Genetics of the Bacterial Cell Wall, Paris, France
3 - INSERM, Groupe AVENIR, Paris, France



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