# Dual transcriptional inhibition of glutamate and alanine racemase is synergistic in Mycobacterium tuberculosis

## TL;DR

This study shows that inhibiting two enzymes together in tuberculosis bacteria has a stronger effect than inhibiting them separately.

## Contribution

The study confirms a synergistic interaction between inhibiting two specific enzymes in Mycobacterium tuberculosis using transcriptional repression.

## Key findings

- Simultaneous repression of glutamate and alanine racemase shows synergy in Mycobacterium tuberculosis.
- This synergy confirms earlier findings from chemical interaction studies.
- Targeting multiple cell wall synthesis enzymes could be a promising strategy for tuberculosis treatment.

## 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.