1. Dual transcriptional inhibition of glutamate and alanine racemase is synergistic in Mycobacterium tuberculosis .
- Author
-
McNeil MB, Cook GM, and Krause KL
- Subjects
- Gene Expression Regulation, Bacterial, Transcription, Genetic, Bacterial Proteins genetics, Bacterial Proteins metabolism, Enzyme Inhibitors pharmacology, Cell Wall metabolism, Cell Wall genetics, Mycobacterium tuberculosis genetics, Mycobacterium tuberculosis enzymology, Mycobacterium tuberculosis drug effects, Amino Acid Isomerases genetics, Amino Acid Isomerases metabolism, Alanine Racemase genetics, Alanine Racemase metabolism
- Abstract
Synergistic interactions between chemical inhibitors, whilst informative, can be difficult to interpret, as chemical inhibitors can often have multiple targets, many of which can be unknown. Here, using multiplexed transcriptional repression, we have validated that the simultaneous repression of glutamate racemase and alanine racemase has a synergistic interaction in Mycobacterium tuberculosis . This confirms prior observations from chemical interaction studies and highlights the potential of targeting multiple enzymes involved in mycobacterial cell wall synthesis.
- Published
- 2024
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