Abstract

β-lactamase inhibitors are clinically proven to revitalize old β-lactam antibiotics by neutralizing bacterial β-lactamases. We call these compounds antibiotic resistance breakers (ARB). Unfortunately, bacteria express more than 1000 β-lactamases, of which the metallo-beta-lactamases are proving difficult to neutralize. Here, we describe other antibiotic resistant breakers, which are not yet in the clinic, but which potentially revitalize other classes of antibiotics. These include aminoglycoside-modifying enzyme inhibitors, efflux pump inhibitors, and compounds that are associated with increased permeability of the bacterial cell membrane. If it were possible to develop new ARB for many different classes of antibiotics, this approach could be a viable alternative to the more expensive single novel compound route that has been pursued for pyogenic bacterial infections.