# MtrR Regulates a Major Lytic Transglycosylase (ltgA) Responsible for Peptidoglycan-Derived Cytotoxin Release and Autolysis in Neisseria gonorrhoeae

## TL;DR

This study shows that MtrR regulates a key enzyme in Neisseria gonorrhoeae that affects cell wall breakdown and toxin release.

## Contribution

The study identifies MtrR as a regulator of ltgA, linking it to peptidoglycan-derived cytotoxin release and autolysis in Neisseria gonorrhoeae.

## Key findings

- MtrR binds to the ltgA promoter and increases its expression during exponential growth.
- Deleting mtrR reduces peptidoglycan monomer release and increases bacterial autolysis.
- MtrR regulation of ltgA impacts cytotoxin release and contributes to gonococcal pathogenesis.

## Abstract

The multiple-transferable resistance protein (MtrR) is a transcriptional repressor of the mtrCDE-encoded drug efflux pump and Type IV pilus biosynthesis (pilM), and an activator of penicillin-binding protein 1 (ponA) expression in Neisseria gonorrhoeae. Previously published microarray data suggested that MtrR is also an activator of ltgA expression in the gonococcus. LtgA is a lytic transglycosylase responsible for approximately half of recycled peptidoglycan fragments and released peptidoglycan-derived cytotoxins, which cause ciliary damage and induce specific inflammatory responses. The fragments generated by LtgA during peptidoglycan remodeling can either be recognized by the permease AmpG for uptake into the bacterial cytoplasm and recycled for new cell wall growth and general metabolism or released into the external milieu. Therefore, we sought to define the capacity of MtrR to regulate LtgA expression in gonococci. We show that MtrR binds to the ltgA promoter region in a concentration-dependent manner, and that this binding results both in increased ltgA mRNA transcription and LtgA protein levels during exponential growth. Deletion of mtrR in N. gonorrhoeae decreased peptidoglycan monomer release from growing cells and increased autolysis. These results suggest that MtrR regulation of ltgA impacts peptidoglycan-derived cytotoxin release and autolysis in the gonococcus. This study suggests a central role of MtrR in coordinating aspects of the cellular envelope that may contribute to gonococcal pathogenesis.