TlyC, a conserved hemolysin in <i>Rickettsia</i> , contributes to spotted fever pathogenesis in mice

Rickettsiosis is a vector-borne disease that causes systemic and potentially fatal vasculitis if not diagnosed promptly and treated with antibiotics. Pathogenic <i>Rickettsia</i> species, such as <i>Rickettsia conorii</i>, preferentially infect vascular endothelial cells with extensive abilities to survive in the cytoplasm of professional phagocytes. With the development of genetic tools for <i>Rickettsia</i>, recent studies have highlighted the biological roles of unique and conserved factors involved in rickettsial pathogenesis and vector transmission. However, additional studies are warranted to uncover essential molecular mechanisms that can be exploited to generate vaccines or therapeutics. The significance of our research is the identification of a conserved hemolysin exhibiting unconventional hemolytic activities and its contribution to rickettsial pathogenesis. Our research establishes a concrete foundation for studying protein secretion pathways that translocate effector proteins in <i>Rickettsia</i>, understanding how <i>Rickettsia</i> controls host cell membrane disruption, and identifying factors that support the rickettsial lifecycle between arthropod vectors and mammalian hosts.