Bacterial multidrug transcriptional regulator (BMTR)

Bacterial multidrug transcriptional regulators are a diverse class of DNA-binding proteins that coordinate the expression of genes involved in antimicrobial resistance, most notably multidrug efflux pumps and outer membrane porins. These regulators, which include members of the MarR, TetR, AraC/XylS, and MerR families, act as molecular switches that sense environmental stressors such as antibiotics, biocides, and host-derived signals (Cuthbertson & Nodwell, 2013; Perera & Grove, 2010). By modulating the transcription of the bacterial resistome, these proteins enable pathogens to survive exposure to structurally diverse antimicrobial agents, often leading to high-level multidrug resistance (MDR) (Li & Nikaido, 2009). In pathogens like Pseudomonas aeruginosa and Escherichia coli, the overactivation of these regulators is a major clinical challenge that renders standard antibiotic therapies ineffective (Blanco et al., 2016). Consequently, these regulators are being investigated as therapeutic targets for antimicrobial adjuvants; inhibiting their activity can re-sensitize bacteria to existing antibiotics by preventing the induction of efflux systems (Piddock, 2006). Such strategies aim to lower the minimum inhibitory concentration (MIC) of antibiotics and extend the clinical utility of the current antimicrobial pharmacopeia (Stavri et al., 2007). These regulators are particularly attractive because they often control multiple resistance mechanisms simultaneously, providing a broad-spectrum approach to overcoming resistance. However, the high diversity of these proteins across different bacterial species presents a significant challenge for the development of universal inhibitors.

Other names

Multidrug resistance regulatorMDR transcriptional regulatorAntibiotic resistance transcription factorEfflux pump regulatorMarR-family regulatorTetR-family regulatorMDR-TR

Inhibition of transcription factor binding to promoter regions or stabilization of repressor-DNA complexes to suppress the expression of multidrug efflux pumps and resistance determinants (Piddock, 2006; Stavri et al., 2007).