Rab GTPase network-driven remodeling of membrane trafficking and intracellular bacterial dynamics during infection

Host cells remodel membrane trafficking pathways in response to microbial invasion as a self-defense strategy. Using an epithelial infection model of Group A Streptococcus (GAS), we have elucidated how Rab GTPase networks dynamically reorganize membrane trafficking to govern the intracellular fate of invading bacteria during infection. Our membrane dynamics analyses of selective autophagy (xenophagy) targeting cytosolic GAS revealed that multiple inter-organelle interactions mediated by an infection-specific Rab repertoire are crucial for antibacterial activity. While GAS-secreted NADase inhibits the canonical PI3P-dependent autophagy pathway, the host counters infection by activating an alternative PI4P-dependent xenophagy pathway through Rab-driven rewiring of membrane transport. Furthermore, our recent work has uncovered multilayered and stage-specific reprogramming of Rab networks during infection, including Rab41-mediated membrane repair and RabGAP1L-Rab11A-dependent bacterial expulsion.