Salmonella Typhimurium effector PipB2 targets Rab14 to impair host autophagic flux and promote intracellular survival.

Salmonella enterica serovar Typhimurium (S. Typhimurium) is a major cause of foodborne infections and represents a significant public health concern. After entering host cells, S. Typhimurium uses effector proteins to support its intracellular survival, but the mechanisms through which these effectors act remain incompletely understood. In this study, we investigated PipB2 as a Salmonella effector associated with increased intracellular bacterial survival and characterized Rab14 as a PipB2-associated host target. We found that recombinant PipB2 directly bound Rab14 and reduced Rab14 GTP hydrolysis in vitro, while the presence of PipB2 in infected cells was associated with increased phosphorylation of AKT and AS160, suggesting that PipB2 may affect Rab14-related host processes and may also be linked to AKT-AS160-associated host signaling. These PipB2-associated changes were accompanied by impaired autophagic flux and increased intracellular bacterial burden, consistent with enhanced intracellular replication. Pharmacological inhibition of AKT with inhibitor VIII partially attenuated PipB2-associated changes in autophagic flux and reduced intracellular bacterial burden both in vitro and in vivo. Our mechanistic investigations provide new insights into how the S. Typhimurium effector PipB2 impairs host autophagic flux and suggest a potential host-directed intervention strategy.