Intracellular passage triggers a molecular response in that increases its infectiousness

Abstract

Brucella abortus is a facultative extracellular-intracellular pathogen that encounters a diversity of environments within the host cell. We report that bacteria extracted from infected cells at late stages (48 h post-infection) of the intracellular life cycle significantly increase their ability to multiply in new target cells. This increase depends on early interaction with the cell surface since bacteria become more adherent and penetrate more efficiently as compared to in vitro grown bacteria. At this late stage of infection, the bacterium locates within an autophagosome-like compartment, facing starving and acidic conditions. At this point, the two-component system BvrR/BvrS becomes activated, and the expression of the transcriptional regulator VjbR and the type IV secretion system VirB increased. Using bafilomycin to inhibit BvrR/BvrS activation and specific inhibitors for VjbR and VirB we showed that the BvrR/BvrS and VjbR systems correlate with the increased interaction with new host cells while the VirB system does not. Bacteria released from infected cells under natural conditions displayed the same phenotype as intracellular bacteria. We propose a model in which the B. abortus BvrR/BvrS system senses the transition from its replicative niche at the endoplasmic reticulum to the autophagosome-like exit compartment. This activation leads to the expression of VirB participating in the release of the bacterium from the cells and an increase in VjbR expression that results in a more efficient interaction with new host cells.