Which Way In? The RalF Arf-GEF Orchestrates Host Cell Invasion

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Phylogenomics analysis indicates divergent mechanisms for host cell invasion across diverse species of obligate intracellular Rickettsia. For instance, only some Rickettsia species carry RalF, the rare bacterial Arf-GEF effector utilized by Legionella pneumophila to facilitate fusion of ER-derived membranes with its host-derived vacuole. For R. prowazekii (Typhus Group, TG), prior in vitro studies suggested the Arf-GEF activity of RalF, which is absent from Spotted Fever Group species, might be spatially regulated at the host plasma membrane. Herein, we demonstrate RalF of R. typhi (TG) and R. felis (Transitional Group) localizes to the host plasma membrane, yet R. bellii (Ancestral Group) RalF shows perinuclear localization reminiscent of RalF-mediated recruitment of Arf1 by L. pneumophila to its vacuole. For R. typhi, RalF expression occurs early during infection, with RalF inactivation significantly reducing host cell invasion. Furthermore, RalF co-localization with Arf6 and the phosphoinositide PI(4,5)P2 at the host plasma membrane was determined to be critical for R. typhi invasion. Thus, our work illustrates that different intracellular lifestyles across species of Rickettsia and Legionella have driven divergent roles for RalF during host cell infection. Collectively, we identify lineage-specific Arf-GEF utilization across diverse rickettsial species, previously unappreciated mechanisms for host cell invasion and infection.

Vyšlo v časopise: Which Way In? The RalF Arf-GEF Orchestrates Host Cell Invasion. PLoS Pathog 11(8): e32767. doi:10.1371/journal.ppat.1005115
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005115

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