Abstract

Brucella is a facultative extracellular-intracellular pathogen that belongs to the Alphaproteobacteria class. Precise sensing of environmental changes and a proper response mediated by a gene expression regulatory network are essential for this pathogen to survive. The plant-related Alphaproteobacteria Sinorhizobium meliloti and Agrobacterium tumefaciens also alternate from a free to a host-associated life, where a regulatory invasion switch is needed for this transition. This switch is composed of a two-component regulatory system (TCS) and a global inhibitor, ExoR. In B. abortus, the BvrR/BvrS TCS is essential for intracellular survival. However, the presence of a TCS inhibitor, such as ExoR, in Brucella is still unknown. In this work, we identified a genomic sequence similar to S. meliloti exoR in the B. abortus 2308W genome, constructed an exoR mutant strain, and performed its characterization through ex vivo and in vivo assays. Our findings indicate that ExoR is related to the BvrR phosphorylation state, and is related to the expression of known BvrR/BrvS gene targets, such as virB8, vjbR, and omp25 when grown in rich medium or starving conditions. Despite this, the exoR mutant strain showed no significant differences as compared to the wild-type strain, related to resistance to polymyxin B or human non-immune serum, intracellular replication, or infectivity in a mice model. ExoR in B. abortus is related to BvrR/BvrS as observed in other Rhizobiales; however, its function seems different from that observed for its orthologs described in A. tumefaciens and S. meliloti.

Highlights

  • Members of the Brucella genus are worldwide distributed zoonotic pathogens that belong to the Alphaproteobacteria class

  • The results show that ExoR affects VirB, Omp25, and VjbR expression dynamics and BvrR phosphorylation, but its absence does not affect B. abortus virulence ex vivo or in vivo

  • Using Basic Local Alignment Search Tool (BLASTp) and the ExoR protein sequence from S. meliloti (GenBank Accession WP_003534542.1) [35, 36] a similar sequence (51% identity), possibly encoding a 267 amino acid residues long protein was found in the B. abortus 2308W genome (GenBank Accession ERS568782) [34]

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Summary

Introduction

Members of the Brucella genus are worldwide distributed zoonotic pathogens that belong to the Alphaproteobacteria class. Infection in humans is associated with diverse and unspecific symptoms, including fever, lassitude, general malaise, weight loss, headache, low back pain, and arthralgias [1]. ExoR is not crucial for Brucella abortus virulence

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