# The LysR-family transcriptional regulator VtlR coordinates carbon metabolism, oxidative and nitrosative stress resistance, and virulence in Brucella melitensis

## TL;DR

This study shows that the VtlR protein is crucial for the survival and virulence of Brucella melitensis, a bacteria that causes brucellosis, and suggests it could be used to develop a vaccine.

## Contribution

The study identifies VtlR's role in B. melitensis and its regulatory targets, revealing its importance for virulence and vaccine potential.

## Key findings

- VtlR is essential for B. melitensis virulence and resistance to oxidative and nitrosative stress.
- VtlR regulates small RNA AbcR2 and three DUF1127-domain proteins, similar to its role in B. abortus.
- The vtlR mutant strain induced protective immunity in mice, suggesting potential as a live-attenuated vaccine.

## Abstract

Brucellosis, a globally significant zoonotic disease caused by Brucella infection, relies on the pathogen’s ability to invade and replicate within host cells. This intracellular replication is tightly regulated by transcriptional networks, including the LysR-family regulator VtlR, which is critical for B. abortus virulence but whose role in B. melitensis remains unclear. Here, we constructed vtlR mutant and complemented strains in B. melitensis M5 and demonstrated that VtlR is essential for virulence. Phenotypic assays revealed that vtlR deletion impaired bacterial growth on L-fucose, D-glucose, and meso-erythritol, increased sensitivity to hydrogen peroxide and sodium nitroprusside, and reduced intracellular survival in RAW264.7 macrophages while triggering reactive oxygen species (ROS) production. RNA-seq and RT-qPCR analysis indicated that VtlR positively regulates small RNA AbcR2 and three DUF1127-domain proteins (RS13565, RS04310, RS13280), mirroring its regulatory role in B. abortus. However, overexpression of these targets failed to restore virulence in the vtlR mutant. Notably, the mutant strain elicited protective immunity in mice, suggesting its potential as a live-attenuated vaccine candidate. Collectively, this study elucidates the VtlR regulon in B. melitensis, advancing our understanding of Brucella pathogenesis and vaccine development.

The online version contains supplementary material available at 10.1186/s13567-025-01658-x.