Bioisosteric replacement of pyridoxal-5'-phosphate to pyridoxal-5'-tetrazole targeting Bacillus subtilis GabR.

ABSTRACT: Antimicrobial resistance is a significant cause of mortality globally due to infections, a trend that is expected to continue to rise. As existing treatments fail and new drug discovery slows, the urgency to develop novel antimicrobial therapeutics grows stronger. One promising strategy involves targeting bacterial systems exclusive to pathogens, such as the transcription regulator protein GabR. Expressed in diverse bacteria including Escherichia coli, Bordetella pertussis, and Klebsiella pneumoniae, GabR has no homolog in eukaryotes, making it an ideal therapeutic target. Bacillus subtilis GabR (bsGabR), the most studied variant, regulates its own transcription and activates genes for GABA aminotransferase (GabT) and succinic semialdehyde dehydrogenase (GabD). This intricate regulatory sy

SUBMITTER: Kaley NE 

PROVIDER: S-EPMC11669113 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature