Antibiotic adjuvants

Abstract

Bacteria are becoming increasingly resistant to currently available antibiotics, and the development of new antibiotics is not keeping pace. Alternative approaches to combatting drug-resistant bacteria are sorely needed. One such approach is the development of small-molecule antibiotic adjuvants. Adjuvants that thwart resistance mechanisms and render bacteria susceptible to antibiotics have the potential to prolong the life span and also to extend the spectrum of our current armamentarium of drugs. Several approaches to the development of potential adjuvant therapeutics have been investigated, based upon combatting various resistance mechanisms, and have identified promising adjuvant classes. These classes include adjuvants that inhibit modification or degradation of the antibiotic by enzymes (such as β-lactamases or the aminoglycoside-modifying enzymes), adjuvants that increase the intracellular concentration of the antibiotic by inhibiting efflux or facilitating antibiotic uptake, adjuvants that interfere with bacterial signaling systems that drive or coordinate resistance mechanisms, and finally adjuvants that target nonessential steps in bacterial cell wall synthesis. The antibiotic adjuvant approach is a promising orthogonal strategy for the development of new antibiotics to combat drug-resistant bacteria.