ChemBioChem 2012-03-05

Identification of a novel protein synthesis inhibitor active against gram-positive bacteria.

Nora R Eibergen, Isak Im, Nisha Y Patel, Paul J Hergenrother

Index: ChemBioChem. 4th ed., 13 , 574-583, (2012)

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Abstract

In an effort to identify novel antibacterial chemotypes, we performed a whole-cell screen for inhibitors of Staphylococcus aureus growth and pursued those compounds with previously uncharacterized antibacterial activity. This process resulted in the identification of a benzothiazolium salt, ABTZ-1, that displayed potent antibacterial activity against Gram-positive pathogens. Several clinically desirable qualities were demonstrated for ABTZ-1 including potent activity against multidrug-resistant clinical isolates of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant enterococci (VRE), retention of this activity in human serum, and low hemolytic activity. The antibacterial activity of ABTZ-1 was attributed to its inhibition of bacterial translation, as this compound prevented the incorporation of [³⁵S]methionine into S. aureus proteins, and ABTZ-1-resistant strains were cross-resistant to known inhibitors of bacterial translation. ABTZ-1 represents a promising new class of antibacterial agents.Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.