BvrR/BvrS-Controlled Outer Membrane Proteins Omp3a and Omp3b Are Not Essential forBrucella abortusVirulence

Abstract

The Brucella abortus two-component regulatory system BvrR/BvrS controls the expression of outer membrane proteins (Omp) Omp3a (Omp25) and Omp3b (Omp22). Disruption of bvrS or bvrR generates avirulent mutants with altered cell permeability, higher sensitivity to microbicidal peptides, and complement. Consequently, the role of Omp3a and Omp3b in virulence was examined. Similar to bvrS or bvrR mutants, omp3a and omp3b mutants displayed increased attachment to cells, indicating surface alterations. However, they showed unaltered permeability; normal expression of Omp10, Omp16, Omp19, Omp2b, and Omp1; native hapten polysaccharide; and lipopolysaccharide and were resistant to complement and polymyxin B at ranges similar to those of the wild-type (WT) counterpart. Likewise, omp3a and omp3b mutants were able to replicate in murine macrophages and in HeLa cells, were resistant to the killing action of human neutrophils, and persisted in mice, like the WT strain. Murine macrophages infected with the omp3a mutant generated slightly higher levels of tumor necrosis factor alpha than the WT, whereas the bvrS mutant induced lower levels of this cytokine. Since the absence of Omp3a or Omp3b does not result in attenuation, it can be concluded that BvrR/BvrS influences additional Brucella properties involved in virulence. Our results are discussed in the light of previous works suggesting that disruption of omp3a generates attenuated Brucella strains, and we speculate on the role of group 3 Omps.

The role of a Brucella abortus lipoprotein in intracellular replication and pathogenicity in experimentally infected mice

“…However, our results suggested that surface protein modification and changed adherent activity were not directly connected with bacterial internalization, at least in our experiments. Indeed, OMP22 and OMP25, the expression of which is regulated by the BvrS/BvrR system, also modified surface properties [29]. However, these OMPs do not influence intracellular survival.…”

Brucella regulators: self-control in a hostile environment

“…Despite the importance of this regulatory system in Brucella virulence, little is known about the genes regulated or the environmental signals sensed by the system. BvrR-BvrS has been shown to regulate expression of outer membrane proteins Omp3a and Omp3b [21,45,47]; however, data indicates that these proteins are not essential for Brucella virulence [48,49]. …”

Pathogenesis and Immunobiology of Brucellosis

“…16,32 The absence of the BvrR/BvrS sensory-regulatory system results in major changes in the bacterial outer membrane that alters cellular uptake of the organism. 33 The BvrR/BvrS regulon also includes carbon and nitrogen metabolic functions and the expression of additional transcriptional regulators among 127 differentially regulated genes. 32 In the absence of a functioning BvrR/BvrS, the organism fails to replicate intracellularly and is avirulent in the mouse model.…”