Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:1.6.5.3 (
complex I
)
8,901
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:Development of a novel rationally designed antibiotic to inhibit a nontraditional bacterial target. 2842 1
