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Structural and functional implications of the interaction between macrolide antibiotics and bile acids.

Glanzer S, Pulido SA, Tutz S, Wagner GE, Kriechbaum M, Gubensäk N, Trifunovic J, Dorn M, Fabian WM, Novak P, Reidl J, Zangger K - Chemistry (2015)

Bottom Line: The macrolides were found to be bound close to the surface of the micelle.The binding to bile aggregates does not impede macrolide antibiotics from targeting bacteria.In fact, the toxicity of azithromycin towards enterotoxic E. coli (ETEC) is even slightly increased in the presence of bile, as was shown by effective concentration (EC50 ) values.

View Article: PubMed Central - PubMed

Affiliation: Institute of Chemistry, University of Graz (Austria).

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Structures and numbering schemes for the macrolides and bile acids used.
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fig01: Structures and numbering schemes for the macrolides and bile acids used.

Mentions: For this study, a series of representative macrolides were used. In particular, the antibiotics azithromycin, erythromycin, and clarithromycin, but also the macrolides azahomoerythromycin, decladinosylazithromycin, and azithromycin aglycone, which show no antimicrobial activity. The chemical structures of all commonly used macrolide antibiotics are very similar. They consist of a 14- or 15-membered alkylated lactone ring with hydroxyl groups on C3, C5, C6, C11, C12 and a desosamine and decladinose on C3 and C5[11] (Figure 1). Human bile mainly consists of bile acids synthesized from cholesterol, with cholic acid and its deoxo derivatives being the most abundant compounds. In natural bile, the concentration of bile salt is about 40 mm.[12] Structurally, bile acids consist of a hydrophobic nonaromatic four-ring system with hydrophilic hydroxyl groups on one side and a side chain with a carboxyl group on the five-membered ring (Figure 1). In some cases, a glycol or taurine is attached to the carboxyl group. Bile acids are amphiphilic and form primary micelles of 2–10 bile acid molecules at lower (5–15 mm) and vesicles (aggregation number 10–100 aggregates) at higher concentrations.[13] The main physiological functions of bile acids are the solubilization and transport of lipids and interaction with lipid soluble vitamins and drugs[13–15].


Structural and functional implications of the interaction between macrolide antibiotics and bile acids.

Glanzer S, Pulido SA, Tutz S, Wagner GE, Kriechbaum M, Gubensäk N, Trifunovic J, Dorn M, Fabian WM, Novak P, Reidl J, Zangger K - Chemistry (2015)

Structures and numbering schemes for the macrolides and bile acids used.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4471570&req=5

fig01: Structures and numbering schemes for the macrolides and bile acids used.
Mentions: For this study, a series of representative macrolides were used. In particular, the antibiotics azithromycin, erythromycin, and clarithromycin, but also the macrolides azahomoerythromycin, decladinosylazithromycin, and azithromycin aglycone, which show no antimicrobial activity. The chemical structures of all commonly used macrolide antibiotics are very similar. They consist of a 14- or 15-membered alkylated lactone ring with hydroxyl groups on C3, C5, C6, C11, C12 and a desosamine and decladinose on C3 and C5[11] (Figure 1). Human bile mainly consists of bile acids synthesized from cholesterol, with cholic acid and its deoxo derivatives being the most abundant compounds. In natural bile, the concentration of bile salt is about 40 mm.[12] Structurally, bile acids consist of a hydrophobic nonaromatic four-ring system with hydrophilic hydroxyl groups on one side and a side chain with a carboxyl group on the five-membered ring (Figure 1). In some cases, a glycol or taurine is attached to the carboxyl group. Bile acids are amphiphilic and form primary micelles of 2–10 bile acid molecules at lower (5–15 mm) and vesicles (aggregation number 10–100 aggregates) at higher concentrations.[13] The main physiological functions of bile acids are the solubilization and transport of lipids and interaction with lipid soluble vitamins and drugs[13–15].

Bottom Line: The macrolides were found to be bound close to the surface of the micelle.The binding to bile aggregates does not impede macrolide antibiotics from targeting bacteria.In fact, the toxicity of azithromycin towards enterotoxic E. coli (ETEC) is even slightly increased in the presence of bile, as was shown by effective concentration (EC50 ) values.

View Article: PubMed Central - PubMed

Affiliation: Institute of Chemistry, University of Graz (Austria).

Show MeSH
Related in: MedlinePlus