The Discovery of 2‐Aminobenzimidazoles That Sensitize <i>Mycobacterium smegmatis</i> and <i>M. tuberculosis</i> to β‐Lactam Antibiotics in a Pattern Distinct from β‐Lactamase Inhibitors

Abstract

A library of 2-aminobenzimidazole derivatives was screened for the ability to suppress β-lactam resistance in Mycobacterium smegmatis. Several non-bactericidal compounds were identified that reversed intrinsic resistance to β-lactam antibiotics in a manner distinct from β-lactamase inhibitors. Activity also translates to M. tuberculosis, with a lead compound from this study potently suppressing carbenicillin resistance in multiple M. tuberculosis strains (including multidrug-resistant strains). Preliminary mechanistic studies revealed that the lead compounds act through a mechanism distinct from that of traditional β-lactamase inhibitors.