Beta-lactamase regulatory protein BlaR (BlaR)

Beta-lactamase regulatory protein BlaR (Rv1845c) is a zinc-dependent metalloprotease in Mycobacterium tuberculosis that serves as a critical regulator of the pathogen's resistance to beta-lactam antibiotics [25, 26]. It functions as a signal transducer that modulates the expression of the broad-spectrum beta-lactamase BlaC by cleaving its transcriptional repressor, BlaI [25, 29]. Under conditions of antibiotic stress, BlaR-mediated proteolysis of BlaI derepresses the blaC operon, allowing the bacteria to produce enzymes that degrade beta-lactam drugs [26, 27]. Recent research, including the Tres Cantos Open Lab Foundation project TC301, has identified BlaR as a novel virulence target [4, 41]. Inhibiting BlaR could potentially restore the efficacy of beta-lactam antibiotics against M. tuberculosis, offering a promising strategy for the development of new combination therapies for drug-resistant tuberculosis [41, 48].

Other names

Rv1845cBlaR1 homologBeta-lactamase sensor/signal transducerTC301 (Project Code)

BlaR functions as a signal transducer that regulates the expression of the broad-spectrum beta-lactamase BlaC by cleaving its transcriptional repressor, BlaI. In response to cell wall stress or beta-lactam exposure, BlaR-mediated proteolysis of BlaI derepresses the blaC operon, leading to the production of beta-lactamase and subsequent antibiotic resistance. Inhibiting BlaR prevents this induction, thereby sensitizing the bacteria to beta-lactam antibiotics.