Navigating collateral sensitivity: insights into the mechanisms and applications of antibiotic resistance trade-offs

Abstract

The swift rise of antibiotic resistance, coupled with limited new antibiotic discovery, presents a significant hurdle to global public health, demanding innovative therapeutic solutions. Recently, collateral sensitivity (CS), the phenomenon in which resistance to one antibiotic increases vulnerability to another, has come to light as a potential path forward in this attempt. Targeting either unidirectional or reciprocal CS holds promise for constraining the emergence of drug resistance and notably enhancing treatment outcomes. Typically, the alteration of bacterial physiology, such as bacterial membrane potential, expression of efflux pumps, cell wall structures, and endogenous enzymatic actions, are involved in evolved collateral sensitivity. In this review, we present a thorough overview of CS in antibiotic therapy, including its definition, importance, and underlying mechanisms. We describe how CS can be exploited to prevent the emergence of resistance and enhance the results of treatment, but we also discuss the challenges and restrictions that come with implementing this practice. Our review underscores the importance of continued exploration of CS mechanisms in the broad spectrum and clinical validation of therapeutic approaches, offering insights into its role as a valuable tool in combating antibiotic resistance.