Strategies to Prolong the Useful Life of Existing Antibiotics and Help Overcoming the Antibiotic Resistance Crisis

Antibiotic resistance occurs through several mechanisms that can coexist simultaneously in the same cell. The main ones include modification of the target, reduced permeability, export by active efflux pumps, sequestration of the drug by tight binding to an endogenous molecule, and enzymatic inactivation of the antibiotic molecule. The development of new antibiotics, a path currently being pursued by several laboratories using different approaches, is an obvious answer to the problem of resistance. However, this solution has not yielded the results one would expect; few new antimicrobials have been generated in the past decades. This article illustrates alternative methodologies that are being explored to produce chemicals that, although not having antimicrobial properties, act as potentiators such that combination therapies including the antibiotic and the adjuvant can overcome resistance. These compounds can achieve the expected outcome by inhibition of expression of resistance traits or interference with the function of components of resistance mechanisms.

Keywords: Antisense, Adjuvant, Aminoglycoside, Aminoglycoside modifying enzymes, Antibiotic resistance, β-lactam, β-lactamase, Efflux pumps, External guide sequence, Nucleic acid analogs.