{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T00:03:44Z","timestamp":1744157024107},"reference-count":57,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,4,21]],"date-time":"2013-04-21T00:00:00Z","timestamp":1366502400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Helicobacter"],"published-print":{"date-parts":[[2013,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>Helicobacter pylori<\/jats:italic>, a neutralophile, colonizes the acidic environment of the human stomach by employing acid acclimation mechanisms that regulate periplasmic and cytoplasmic <jats:styled-content style=\"fixed-case\">pH<\/jats:styled-content>. The regulation of urease activity is central to acid acclimation. Inactive urease apoenzyme, <jats:styled-content style=\"fixed-case\">U<\/jats:styled-content>re<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>, requires nickel for activation. Accessory proteins UreE, F, G, and H are required for nickel insertion into apoenzyme. The <jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>xb<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>xb<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>on<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content> complex transfers energy from the inner to outer membrane, providing the driving force for nickel uptake. Therefore, the aim of this study was to determine the contribution of <jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>xb<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content> to <jats:styled-content style=\"fixed-case\">pH<\/jats:styled-content> homeostasis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>A nonpolar <jats:italic>exbD<\/jats:italic> knockout was constructed and survival, growth, urease activity, and membrane potential were determined in comparison with <jats:italic>wildtype<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Survival of the <jats:italic>\u0394exbD<\/jats:italic> strain was significantly reduced at <jats:styled-content style=\"fixed-case\">pH<\/jats:styled-content> 3.0. Urease activity as a function of <jats:styled-content style=\"fixed-case\">pH<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">U<\/jats:styled-content>reI activation was similar to the <jats:italic>wildtype<\/jats:italic> strain, showing normal function of the proton\u2010gated urea channel, <jats:styled-content style=\"fixed-case\">U<\/jats:styled-content>reI. The increase in total urease activity over time in acid seen in the <jats:italic>wildtype<\/jats:italic> strain was abolished in the <jats:italic>\u0394exbD<\/jats:italic> strain, but recovered in the presence of supraphysiologic nickel concentrations, demonstrating that the effect of the <jats:italic>\u0394exbD<\/jats:italic> mutant is due to loss of a necessary constant supply of nickel. In acid, <jats:italic>\u0394exbD<\/jats:italic> also decreased its ability to maintain membrane potential and periplasmic buffering in the presence of urea.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>ExbD is essential for maintenance of periplasmic buffering and membrane potential by transferring energy required for nickel uptake, making it a potential nonantibiotic target for <jats:italic>H.\u00a0pylori<\/jats:italic> eradication.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hel.12055","type":"journal-article","created":{"date-parts":[[2013,4,22]],"date-time":"2013-04-22T03:36:49Z","timestamp":1366601809000},"page":"363-372","source":"Crossref","is-referenced-by-count":15,"title":["The Role of <scp>E<\/scp>xb<scp>D<\/scp> in Periplasmic <scp>pH<\/scp> Homeostasis in <i><scp>H<\/scp>elicobacter pylori<\/i>"],"prefix":"10.1111","volume":"18","author":[{"given":"Elizabeth A.","family":"Marcus","sequence":"first","affiliation":[{"name":"Department of Pediatrics 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