Cell-selective proteomics reveal novel effectors secreted by an obligate intracellular bacterial pathogen.

Autor: Sanderlin, Allen G., Kurka Margolis, Hannah, Meyer, Abigail F., Lamason, Rebecca L.
Předmět:
Zdroj: Nature Communications; 7/18/2024, Vol. 15 Issue 1, p1-15, 15p
Abstrakt: Pathogenic bacteria secrete protein effectors to hijack host machinery and remodel their infectious niche. Rickettsia spp. are obligate intracellular bacteria that can cause life-threatening disease, but their absolute dependence on the host cell has impeded discovery of rickettsial effectors and their host targets. We implemented bioorthogonal non-canonical amino acid tagging (BONCAT) during R. parkeri infection to selectively label, isolate, and identify effectors delivered into the host cell. As the first use of BONCAT in an obligate intracellular bacterium, our screen more than doubles the number of experimentally validated effectors for the genus. The seven novel secreted rickettsial factors (Srfs) we identified include Rickettsia-specific proteins of unknown function that localize to the host cytoplasm, mitochondria, and ER. We further show that one such effector, SrfD, interacts with the host Sec61 translocon. Altogether, our work uncovers a diverse set of previously uncharacterized rickettsial effectors and lays the foundation for a deeper exploration of the host-pathogen interface. Rickettsia species secrete effector proteins into host cells to promote infection, but few effectors have been identified. Here, Sanderlin et al use a protein labeling approach to identify an expanded repertoire of effectors acting at the host-pathogen interface. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index