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Understanding the link between antimicrobial properties of safranal and microbial ATP synthase
Author(s) -
Liu Mason,
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.921.6
Subject(s) - atp synthase , biochemistry , safranal , chemistry , escherichia coli , antimicrobial , mutant , biology , enzyme , microbiology and biotechnology , gene , crocin
Background A variety of phytochemicals with antimicrobial and antitumor properties have been identified to bind and inhibit ATP synthase. Saffron constituent safranal and its analogs are known to have antitumor, cytotoxic, and antimicrobial properties. Our lab has studied safranal and its structural analogs, thymol, cuminol, carvacrol, damascenone, 2,6,6‐trimethyl‐2‐cyclohexene‐1,4‐dione, and 4‐isoproply benzyl bromide induced‐inhibition of Escherichia coli ATP synthase and their effect on cell growth to investigate any link between antimicrobial properties of these compounds and ATP synthase inhibition. Methods Wild type and mutant E. coli strains were grown to late log phase. Cells were harvested by centrifugation and lysed by French Press to isolate the membrane bound F 1 F O ATP synthase. Null E. coli strain pUC118 with deleted ATPase gene was used as a negative control. Safranal and its analogs induced inhibitory studies were performed on membrane bound F 1 F O ATP synthase. Growth of wild‐type, mutant, and null strain in limiting glucose and succinate was also examined in presence and absence of safranal and its analogs. Results Safranal and its analogs inhibited wild‐type enzyme to variable degrees. While safranal caused 100% inhibition of wild‐type F 1 F O ATP synthase, only ~50% inhibition occurred for the mutant ATP synthase. Inhibitory profiles of mutant E. coli strains indicated the involvement of specific amino acids in the binding of safranal and its analogs to ATP synthase. Furthermore, safranal, thymol, cuminol, carvacrol, and damascenone fully abrogated the growth of wild‐type E. coli cells and had little or no effect on the growth of null and mutant E. coli strains. Conclusions Safranal and its analogs appear to bind to the polyphenol binding pocket on F 1 sector of ATP synthase. The antimicrobial properties of safranal and its analogs can be linked to their binding and inhibition of ATP synthase. Thus, our results support the idea that ATP synthase can be used as a 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 # 850‐619 to ML and ZA.