FIG 7.

Schematic of PI metabolism during R. typhi entry. Upon engagement with host cells, we previously demonstrated that R. typhi secretes RalF via its type IV secretion system, resulting in recruitment of host Arf6 to PI(4,5)P₂-enriched regions of the PM (48). Here we show that Arf6 is activated during R. typhi infection, leading to recruitment of PIP5K, which is critical for R. typhi infection (steps 1 to 3). Additionally, we established the downstream effects of this process by characterizing PI3K-mediated formation of the phagocytic cup and early endosome (steps 4 and 5). Following entry, R. typhi quickly escapes the phagocytic vacuole to reside within the cytoplasm of the host cell (steps 6 and 7).