Cell-to-cell transmission of Brucella abortus

Abstract

Brucella abortus is a persistent intracellular pathogen capable of evading early immune responses. To explore the mechanism of exit of this bacterium, we monitored Brucella infection by live cell imaging for up to 100 hours. This approach uncovered various modes of bacterial spreading, including individual organisms, bacteria-containing vacuoles, and direct transmission between cells (called cell-to-cell transmission), each fueling new infections. This dissemination occurred regardless of antibiotic presence in the extracellular milieu. While receptor blockade using heparin suppressed free bacterial infections, it promoted cell-to-cell transmission, dependent on cell density. Cells participating in intercellular transmission survived longer than their non-infected counterparts. These observations underscore the adaptability of Brucella for propagating across diverse conditions. ImportanceThe intracellular life cycle of pathogenic bacteria encompasses adhesion, invasion, intracellular replication, and eventual exit from host cells. The exit phase is a critical step for pathogen persistence and dissemination to new hosts. Despite its relevance, the egress mechanisms of Brucella spp. remain largely unexplored. In this study, we describe three distinct modes of Brucella abortus exit: individual bacteria, bacterial clumps, and through direct cell-to-cell transmission. The latter may facilitate immune evasion by bypassing extracellular exposure, thereby contributing to the stealthy survival strategy of Brucella. The presence of multiple egress mechanisms suggests that B. abortus tailors its exit strategies according to its intracellular biogenesis and environmental cues.These findings not only advance our understanding of Brucella pathogenesis but also highlight potential avenues for targeting bacterial dissemination and persistence.