{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T12:29:08Z","timestamp":1789907348820,"version":"4.0.1"},"reference-count":24,"publisher":"Canadian Science Publishing","issue":"5","license":[{"start":{"date-parts":[[2017,5,1]],"date-time":"2017-05-01T00:00:00Z","timestamp":1493596800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.nrcresearchpress.com\/page\/about\/CorporateTextAndDataMining"}],"content-domain":{"domain":["cdnsciencepub.com"],"crossmark-restriction":false},"short-container-title":["Can. J. Physiol. Pharmacol."],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:p> The search for new nontraditional targets is a high priority in antibiotic design today. Bacterial membrane energetics based on sodium ion circulation offers potential alternative targets. The present work identifies the Na<jats:sup>+<\/jats:sup>-translocating NADH:ubiquinone oxidoreductase (Na<jats:sup>+<\/jats:sup>-NQR), a key respiratory enzyme in many microbial pathogens, as indispensible for the Chlamydia trachomatis infectious process. Infection by Chlamydia trachomatis significantly increased first H<jats:sup>+<\/jats:sup> and then Na<jats:sup>+<\/jats:sup> levels within the host mammalian cell. A newly designed furanone Na<jats:sup>+<\/jats:sup>-NQR inhibitor, PEG-2S, blocked the changes in both H<jats:sup>+<\/jats:sup> and Na<jats:sup>+<\/jats:sup> levels induced by Chlamydia trachomatis infection. It also inhibited intracellular proliferation of Chlamydia trachomatis with a half-minimal inhibitory concentration in the submicromolar range but did not affect the viability of mammalian cells or bacterial species representing benign intestinal microflora. At low nanomolar concentrations (IC<jats:sub>50<\/jats:sub> value = 1.76 nmol\/L), PEG-2S inhibited the Na<jats:sup>+<\/jats:sup>-NQR activity in sub-bacterial membrane vesicles isolated from Vibrio cholerae. Taken together, these results show, for the first time, that Na<jats:sup>+<\/jats:sup>-NQR is critical for the bacterial infectious process and is susceptible to a precisely targeted bactericidal compound in situ. The obtained data have immediate relevance for many different diseases caused by pathogenic bacteria that rely on Na<jats:sup>+<\/jats:sup>-NQR activity for growth, including sexually transmitted, pulmonary, oral, gum, and ocular infections. <\/jats:p>","DOI":"10.1139\/cjpp-2016-0505","type":"journal-article","created":{"date-parts":[[2017,4,20]],"date-time":"2017-04-20T11:01:26Z","timestamp":1492686086000},"page":"595-603","update-policy":"https:\/\/doi.org\/10.1139\/csp-crossmark-policy","source":"Crossref","is-referenced-by-count":29,"title":["Development of a novel rationally designed antibiotic to inhibit a nontraditional bacterial target"],"prefix":"10.1139","volume":"95","author":[{"given":"Pavel","family":"Dibrov","sequence":"first","affiliation":[{"name":"Department of Microbiology, Faculty of Science, University of Manitoba, Winnipeg, MB R3T 2N2, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Dibrov","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Sciences, Albrechtsen Research Centre, St. Boniface Hospital, Winnipeg, MB R2H 2A6, Canada."},{"name":"Department of Physiology and Pathophysiology, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3T 2N2, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thane G.","family":"Maddaford","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Sciences, Albrechtsen Research Centre, St. Boniface Hospital, Winnipeg, MB R2H 2A6, Canada."},{"name":"Department of Physiology and Pathophysiology, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3T 2N2, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Kenneth","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Sciences, Albrechtsen Research Centre, St. Boniface Hospital, Winnipeg, MB R2H 2A6, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan","family":"Nelson","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Sciences, Albrechtsen Research Centre, St. Boniface Hospital, Winnipeg, MB R2H 2A6, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Resch","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Science, University of Manitoba, Winnipeg, MB R3T 2N2, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grant N.","family":"Pierce","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Sciences, Albrechtsen Research Centre, St. Boniface Hospital, Winnipeg, MB R2H 2A6, Canada."},{"name":"Department of Physiology and Pathophysiology, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3T 2N2, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"155","reference":[{"key":"refg1\/ref1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(04)00312-6"},{"key":"refg2\/ref2","unstructured":"CLSI. 2012. 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