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Differential Antibacterial Properties of the MurA Inhibitors Terreic Acid and Fosfomycin

Differential Antibacterial Properties of the MurA Inhibitors Terreic Acid and Fosfomycin

Sanne H Olesen, Donna J Ingles, Yan Yang, Ernst Schönbrunn

J Basic Microbiol. 2014 Apr;54(4):322-6.

PMID: 23686727

Abstract:

Terreic acid is a metabolite with antibiotic properties produced by the fungus Aspergillus terreus, but its cellular target remains unknown. We recently reported that terreic acid inactivates the bacterial cell wall biosynthetic enzyme MurA in vitro by covalent reaction with residue Cys115 in a similar manner as the MurA-specific antibiotic fosfomycin. To address if terreic acid also targets MurA in vivo, we conducted antibacterial studies using selected E. coli strains in parallel with fosfomycin. While overexpression of MurA conferred resistance to fosfomycin, it did not protect cells treated with terreic acid. Furthermore, flow cytometry revealed that the antibiotic action of terreic acid appears to be primarily bacteriostatic, as opposed to the bactericidal action observed for fosfomycin. Combined, the data suggest that MurA is not the molecular target of terreic acid and that the antibiotic activity of terreic acid proceeds through a different mechanism of action. The methodology applied here provides a reliable and convenient tool to rapidly assess the potential of newly discovered in vitro inhibitors to target residue Cys115 of MurA in the cell.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP121404-B	Terreic Acid		121-40-4	Price

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