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.

The inside cover picture shows the inhibition of ribosomal protein synthesis in Staphylococcus aureus by the benzothiazolium salt, ABTZ-1. This antibacterial, which inhibits the growth of multidrug-resistant Gram-positive bacteria, prevents the incorporation of radiolabeled methionine into S. aureus protein.Strains resistant to ABTZ-1 also display cross-resistance to fusidic acid and streptogramins. For more information on the discovery and characterization of ABTZ-1 by P. J. Hergenrother et al., see p. 574 ff.