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.
