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- W2605559231 abstract "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 + -translocating NADH:ubiquinone oxidoreductase (Na + -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 + and then Na + levels within the host mammalian cell. A newly designed furanone Na + -NQR inhibitor, PEG-2S, blocked the changes in both H + and Na + 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 50 value = 1.76 nmol/L), PEG-2S inhibited the Na + -NQR activity in sub-bacterial membrane vesicles isolated from Vibrio cholerae. Taken together, these results show, for the first time, that Na + -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 + -NQR activity for growth, including sexually transmitted, pulmonary, oral, gum, and ocular infections." @default.
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- W2605559231 date "2017-05-01" @default.
- W2605559231 modified "2023-09-29" @default.
- W2605559231 title "Development of a novel rationally designed antibiotic to inhibit a nontraditional bacterial target" @default.
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- W2605559231 doi "https://doi.org/10.1139/cjpp-2016-0505" @default.
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