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A 3' SSCR is also present in the <jats:italic>rdxA<\/jats:italic> homolog of <jats:italic>H. heilmannii<\/jats:italic> sensu stricto, but not in <jats:italic>H. pylori<\/jats:italic>. We showed that in the majority of in vitro spontaneous <jats:italic>H. bizzozeronii<\/jats:italic> metronidazole resistant mutants, the extension of the 3\u2032 SSCR of <jats:italic>rdxA<\/jats:italic> was the only mutation observed. In addition, we observed that <jats:italic>H. bizzozeronii<\/jats:italic> \u0394<jats:italic>rdxA<\/jats:italic> mutant strain showed the same MIC value of metronidazole observed in the spontaneous mutants. These data indicate that loss of function mutations in <jats:italic>rdxA<\/jats:italic> and in particular the disruption of the conserved region IACLXALGK is associated with reduced susceptibility to metronidazole in <jats:italic>H. bizzozeronii<\/jats:italic>. Slipped-strand mispairing of the SSCR located in the 3\u2032 of the <jats:italic>H. bizzozeronii rdxA<\/jats:italic> appears to be the main mechanism. We also observed that <jats:italic>H. bizzozeronii<\/jats:italic> acquires resistance to metronidazole at high mutation rate, and that serial passages in vitro without selection induced an increased level of susceptibility. In conclusion, contrary to what was previously described in <jats:italic>H. pylori<\/jats:italic>, the <jats:italic>H. bizzozeronii rdxA<\/jats:italic> appears to be a contingency gene which undergoes phase variation. The contingency nature of <jats:italic>rdxA<\/jats:italic> should be carefully considered when metronidazole is used in the treatment of <jats:italic>H. heilmannii<\/jats:italic>-associated gastritis.<\/jats:p>","DOI":"10.1186\/1297-9716-44-56","type":"journal-article","created":{"date-parts":[[2013,7,16]],"date-time":"2013-07-16T16:14:34Z","timestamp":1373991274000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Contingency nature of Helicobacter bizzozeronii oxygen-insensitive NAD(P)H-nitroreductase (HBZC1_00960) and its role in metronidazole resistance"],"prefix":"10.1186","volume":"44","author":[{"given":"Pradeep Kumar","family":"Kondadi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Pacini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joana","family":"Revez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marja-Liisa","family":"H\u00e4nninen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirko","family":"Rossi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2013,7,16]]},"reference":[{"key":"267_CR1","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1056\/NEJMra020542","volume":"347","author":"S Suerbaum","year":"2002","unstructured":"Suerbaum S, Michetti P: Helicobacter pylori infection. 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