Antibiotic resistance gene expression pathways

Antibiotic resistance gene expression pathways are the coordinated molecular systems that bacteria use to control the production of proteins that provide resistance to antimicrobial drugs [1, 4]. These pathways include global transcriptional regulators like the MarRAB operon, two-component systems such as VanRS, and RNA-based regulatory elements like riboswitches and T-box leaders [1, 2, 33]. They allow bacteria to sense the presence of antibiotics or environmental stress and respond by upregulating efflux pumps, antibiotic-inactivating enzymes, or target-protection proteins [1, 4, 30]. Because these pathways are essential for the phenotypic expression of resistance, they are increasingly viewed as promising therapeutic targets [2, 14]. Inhibiting these pathways can potentially re-sensitize multidrug-resistant bacteria to existing antibiotics or prevent the development of resistance during the course of therapy [9, 26]. Current research focuses on small molecules that disrupt transcription factor binding, antisense agents that block translation, and compounds that target conserved RNA structures in bacterial pathogens [2, 9, 16, 21].

Other names

Bacterial resistance regulatory networksAMR gene regulationTranscriptional regulation of antibiotic resistanceResistance regulonsAdaptive resistance pathways

Inhibition of global transcriptional regulators (e.g., MarA), blocking of RNA-based regulatory elements (e.g., T-box leaders), disruption of signal transduction in two-component systems (e.g., histidine kinase inhibition), and antisense-mediated silencing of resistance genes [2, 9, 14, 16, 21].