Brucella abortus Senses the Intracellular Environment through the BvrR/BvrS Two-Component System, Which Allows B. abortus To Adapt to Its Replicative Niche

Abstract

is a facultative extracellular-intracellular pathogen belonging a group of α-Proteobacteria that establishes close interactions with animal cells. This bacterium enters host cells in a membrane bound compartment, avoiding the lysosomal route and reaching the endoplasmic reticulum through the action of the Type IV secretion system, VirB. In this work we demonstrate that the two-component system BvrR/BvrS senses the intracellular environment to mount the transcriptional response required for intracellular life adaptation. By combining a method to purify intracellularly extracted bacteria with a strategy that allows direct determination of BvrR phosphorylation we showed that upon entrance to host cells, the regulatory protein BvrR was activated (BvrR-P) by phosphorylation at aspartate 58. This activation takes place in response to intracellular cues found in early compartments, such as low pH and nutrient deprivation. Furthermore, BvrR activation was followed by an increase in the expression of VjbR and VirB. The activation of this BvrR-P/VjbR/VirB virulence circuit rescued from the inhibition of intracellular replication induced by bafilomycin treatment of cells, demonstrating the relevance of this mechanism for the intracellular bacterial survival and replication. Altogether, our results indicate that senses the transition from the extracellular to the intracellular milieu through BvrR/BvrS allowing the bacterium to transit safely to its replicative niche. These results serve as a working model for understanding the role of this family of two-component systems in the adaptation to intracellular life of α-Proteobacteria.

Genome‐wide identification of genes directly regulated by ChvI and a consensus sequence for ChvI binding in Sinorhizobium meliloti

“…ExoS/ChvI has orthologs in related α-proteobacteria (Vanderlinde and Yost, 2012;Heavner et al, 2015), and orthologs such as BvrS/BvrR in the mammalian pathogen Brucella abortus and ChvG/ChvI in the plant pathogen Agrobacterium tumefaciens are required for virulence (Charles and Nester, 1993;Sola-Landa et al, 1998;Heavner et al, 2015). ChvG/ChvI-dependent transcription is activated by acidic pH and BvrS/BvrR-dependent transcription is activated by acidic pH and nutrient limitation (Yuan et al, 2008;Altamirano-Silva et al, 2018).…”

The pneumococcal two-component system VisRH is linked to enhanced intracellular survival ofStreptococcus pneumoniaein influenza-infected pneumocytes

“…Many bacterial TCSs, have been involved in intracellular survival mechanisms in eukaryotic cells, such as EvgSA in Shigella flexneri [49]; ArcAB [50], PhoPQ [51] and EnvZ/OmpR [52] in Salmonella thyphimurium ; SrrAB [53]; GraSR [54] in Staphylococcus aureus ; PhoPQ in Escherichia coli [55]; BvrSR in Brucella abortus [56]; and PrrAB in Mycobacterium tuberculosis [57], among others. In S. pneumoniae , most of the TCSs are required for full virulence in animal models of infection [58, 59] and we have shown that two of these systems, StkP/ComE and CiaRH [15, 16], are important in response to acidic and/or oxidative stress.…”

Pathogenesis of brucellosis: analysis of the immunopathological concept

“…У бруцелл описаны растворимые периплазматические белки EipA, EipB наружной мембраны, которые способствуют не только сохранению целостности клеточной оболочки, но и делению бруцелл внутри фагоцитов [31,32].…”