B artonella entry mechanisms into mammalian host cells

Summary The G ram‐negative genus B artonella comprises arthropod‐borne pathogens that typically infect mammals in a host‐specific manner. B artonella bacilliformis and B artonella quintana are human‐specific pathogens, while several zoonotic bartonellae specific for diverse animal hosts infect humans as an incidental host. Clinical manifestations of B artonella infections range from mild symptoms to life‐threatening disease. Following transmission by blood‐sucking arthropods or traumatic contact with infected animals, bartonellae display sequential tropisms towards endothelial and possibly other nucleated cells and erythrocytes, the latter in a host‐specific manner. Attachment to the extracellular matrix ( ECM ) and to nucleated cells is mediated by surface‐exposed bacterial adhesins, in particular trimeric autotransporter adhesins ( TAA s). The subsequent engulfment of the pathogen into a vacuolar structure follows a unique series of events whereby the pathogen avoids the endolysosomal compartments. For B artonella henselae and assumingly most other species, the infection process is aided at different steps by B artonella effector proteins ( B eps). They are injected into host cells through the type IV secretion system ( T 4 SS ) V ir B / D 4 and subvert host cellular functions to favour pathogen uptake. Bacterial binding to erythrocytes is mediated by T rw, another T 4 SS , in a strictly host‐specific manner, followed by pathogen‐forced uptake involving the Ial B invasin and subsequentreplication and persistence within a membrane‐bound intra‐erythrocytic compartment.