Brucella spp. are Gram-negative bacteria that cause brucellosis, one of the most worldwide-distributed zoonosis that affects a broad range of mammals, including humans. This pathogen has the ability to replicate in macrophages and dendritic cells subverting the host’s immune response and establishing chronic infections. Our laboratory is interested in studying the molecular determinants that allow Brucella to survive intracellularly and attempts to understand how it manages to circumvent the host response to establish long-lasting infections.
As an Innovation Fund investigator, Juan E. Ugalde, Ph.D., is teaming with Carlos O. Arregui, Ph.D, to explore the role of the bacterial outer membrane vesicles (OMVs) in pathogen-host interactions. Bacteria use specialized secretion systems to deliver and introduce virulence factors into host cells. Brucella species, which can cause illness in humans as a consequence of exposure to infected animals, and many other Gram-negative bacteria produce OMVs. OMVs are spherical buds of the outer membrane enriched with bacterial enzymes, toxins, and virulence factors. Recently, the team discovered that one of the components of Brucella OMVs induces massive extension of filopodial-like projections by host cells. They propose that Brucella-induced morphological changes are caused by fusion of OMVs with the host plasma membrane, resulting in insertion and/or delivery of factors that can then exert modulatory effects on the host cell’s cytoskeleton. Combining expertise in the study of Brucella host-interactions and cell-to-cell adhesion mechanisms, the team will incorporate approaches from biochemical, biophysical, and imaging methodologies to define the components of Brucella OMVs and determine the molecular mechanisms involved in inducing host cell extensions during bacteria and host cell contacts. The project will provide critical insights into OMVs as an effective and probably a general mechanism used by bacteria to invade host cells, work that could result in new strategies for early infection intervention and disease prevention.