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ATP synthase: a molecular drug target for olive oil constituent tyrosol and its analogs
Author(s) -
Amini Amon,
Ahmad Zulfiqar
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.921.5
Subject(s) - hydroxytyrosol , tyrosol , oleuropein , biochemistry , atp synthase , chemistry , enzyme , mutant , polyphenol , fatty acid synthase , antioxidant , gene
Background A wide range of natural and synthetic compounds including dietary polyphenols are known to bind and inhibit ATP synthase. Dietary polyphenols can be found in a variety of fruits and vegetables such as olives, grapes, tea, coffee, etc. Polyphenols from olives and extra virgin olive oil are known to exhibit antimicrobial, anticancer, and antioxidant properties. Our lab is interested in understanding if the antimicrobial properties of polyphenols are linked to the selective inhibition of microbial ATP synthase. In this study, we examined the inhibitory profiles of Escherichia coli membrane‐bound ATP synthase and cell growth in the presence and absence of olive oil constituent tyrosol and its analogs; hydroxytyrosol, oleuropein, and dihydroxyphenylglycol. Methods Wild type E. coli pBWU13.4 and mutant strains were grown on minimal media to late log phase. Cells were harvested and then French Pressed to isolate and purify membrane‐bound F 1 F O ATP synthase. E. coli pUC118 with deleted ATPase gene was used as null control. Tyrosol and its analogs induced inhibitory profiles of wild‐type and mutant membrane‐bound enzymes were performed at 37 °C. Wild‐type, mutant, and null cell growth assays on limiting glucose were evaluated at OD 595 using an AccuSkan Plate reader over a 24 hour period. Results Tyrosol and its analogs induced a variable degree of ATP synthase inhibition. While tyrosol induced 100% inhibition of wild‐type ATP synthase, hydroxytyrosol, oleuropein, and dihydroxyphenylglycol induced between 40–60% inhibition. Degree of inhibition was also variable for mutant enzymes. Also, tyrosol and its analogs caused variable abrogation of wild‐type, mutant, and null cell growth. Conclusions Tyrosol and its analogs induced inhibitory profiles of membrane bound ATP synthase along with the variable effect on E. coli growth suggests that the antimicrobial properties of tyrosol and its analogs can be associated to the inhibition of ATP synthase. Thus, ATP synthase seems to be a potential molecular drug target to combat microbial infections. Support or Funding Information This work was supported by the National Institutes of Health Grant GM085771 to ZA and KCOM Biomedical Sciences Graduate Program Grant Award # 850‐611 to AA and ZA.