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It is therefore necessary to study the mechanism of multidrug resistance of <jats:italic>H pylori<\/jats:italic>. We have previously identified that the HP0939, HP0497, and HP0471 transporters affect the efflux of drugs from <jats:italic>H pylori<\/jats:italic>. As efflux pumps participate in bacterial multidrug resistance and biofilm formation, we hypothesized that these transporters could be involved in the multidrug resistance and biofilm formation of <jats:italic>H pylori<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>We therefore constructed three knockout strains, <jats:italic>\u0394hp0939<\/jats:italic>, <jats:italic>\u0394hp0497<\/jats:italic>, and <jats:italic>\u0394hp0471<\/jats:italic>, and three high\u2010expression strains, <jats:italic>Hp0939<jats:sup>he<\/jats:sup><\/jats:italic>, <jats:italic>Hp0497<jats:sup>he<\/jats:sup><\/jats:italic>, and <jats:italic>Hp0471<jats:sup>he<\/jats:sup><\/jats:italic>, using the wild\u2010type (WT) 26\u00a0695 strain of <jats:italic>H pylori<\/jats:italic> as the template. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of wild strains, knockout strains, and high\u2010expression strains to amoxicillin, metronidazole, and other antibiotics were measured. The efflux capacity of high\u2010expression strains and wild strains was compared by Hoechst 33\u00a0342 accumulation assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Determination of the MIC and MBC of the antibiotics revealed that the knockout strains were more sensitive to antibiotics, while the high\u2010expression strains were less sensitive to antibiotics, compared to the WT. The ability of the high\u2010expression strains to efflux drugs was significantly higher than that of the WT. We also induced <jats:italic>H pylori<\/jats:italic> to form biofilms, and observed that the knockout strains could barely form biofilms and were more sensitive to several antibiotics, compared to the WT. The mRNA expression of <jats:italic>hp0939, hp0497,<\/jats:italic> and <jats:italic>hp0471<\/jats:italic> in the clinically sensitive and multidrug\u2010resistant strains was determined, and it was found that these genes were highly expressed in the multidrug\u2010resistant strains that were isolated from the clinics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In this study, we found three transporters involved in intrinsic multidrug resistance of <jats:italic>H pylori<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hel.12715","type":"journal-article","created":{"date-parts":[[2020,6,17]],"date-time":"2020-06-17T05:21:31Z","timestamp":1592371291000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Transporters HP0939, HP0497, and HP0471 participate in intrinsic multidrug resistance and biofilm formation in <i>Helicobacter pylori<\/i> by enhancing drug efflux"],"prefix":"10.1111","volume":"25","author":[{"given":"Yuying","family":"Cai","sequence":"first","affiliation":[{"name":"Department of Microbiology Key Laboratory of Medical Microbiology and Parasitology Guizhou Medical University Guiyang China"},{"name":"Institute of Pathogen Biology School of Basic Medical Sciences Shandong University Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caixia","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Microbiology Key Laboratory of Medical Microbiology and Parasitology Guizhou Medical University Guiyang China"},{"name":"Institute of Pathogen Biology School of Basic Medical Sciences Shandong University Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2944-6001","authenticated-orcid":false,"given":"Zhenghong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Microbiology Key Laboratory of Medical 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