Helicobacter pylori gene silencing in vivo demonstrates urease is essential for chronic infection

• DOI: 10.1371/journal.ppat.1006464
• Publication Date: 2017-06-23T17:48:35Z
• Authors: Aleksandra W. Deb...; Senta M. Walton; Eng-Guan Chua; Alfred Chin-Yen Tay; Tingting Liao; Binit Lamichhane; Robyn Himbeck; Keith A. Stubbs; Barry J. Marshall; Alma Fulurija; Mohammed Benghezal
• Keywords: Virulence factor; Chronic infection; CagA

Helicobacter pylori infection causes chronic active gastritis that after many years of can develop into peptic ulceration or gastric adenocarcinoma. The bacterium is highly adapted to surviving in the environment and a key adaptation virulence factor urease. Although widely postulated, requirement urease expression for persistent has not been elucidated experimentally as conventional knockout mutants are incapable colonization. To overcome this constraint, conditional H. were constructed by adapting tetracycline inducible system enabled changing phenotype bacteria during established infection. Through tight regulation we demonstrate only required establishing initial colonization but also maintaining Furthermore, successful isolation tet-escape from late time point revealed strong selective pressure on pathogen continuously express order maintain In addition mutations gene system, escape found harbor changes other genes including alternative RNA polymerase sigma factor, fliA, highlighting genetic plasticity adapt niche. tet-system described here opens up opportunities studying involved stage gain insight bacterial mechanisms promoting immune life-long tool allows new avenue inquiry understanding importance various determinants biological when put under duress.