Abstract
Salmonella Infantis has emerged as a major clinical pathogen causing gastroenteritis worldwide in recent years. As an intracellular pathogen, Salmonella has evolved to manipulate and benefit from the cell death signaling pathway. In this study, we discovered that S. Infantis inhibited apoptosis of infected Caco-2 cells by phosphorylating Akt. Notably, Akt phosphorylation was observed in a discontinuous manner: immediately 0.5 h after the invasion, then before peak cytosolic replication. Single-cell analysis revealed that the second phase was only induced by cytosolic hyper-replicating bacteria at 3–4 hpi. Next, Akt-mediated apoptosis inhibition was found to be initiated by Salmonella SopB. Furthermore, Akt phosphorylation increased mitochondrial localization of Bcl-2 to prevent Bax oligomerization on the mitochondrial membrane, maintaining the mitochondrial network homeostasis to resist apoptosis. In addition, S. Infantis induced pyroptosis, as evidenced by increased caspase-1 (p10) and GSDMS-N levels. In contrast, cells infected with the ΔSopB strain displayed faster but less severe pyroptosis and had less bacterial load. The results indicated that S. Infantis SopB–mediated Akt phosphorylation delayed pyroptosis, but aggravated its severity. The wild-type strain also caused more severe diarrhea and intestinal inflammatory damage than the ΔSopB strain in mice. These findings revealed that S. Infantis delayed the cells’ death by intermittent activation of Akt, allowing sufficient time for replication, thereby causing more severe inflammation.
Highlights
Non-typhoidal salmonella (NTS) has been one of the most common foodborne zoonosis pathogens worldwide that cause host gastroenteritis
Salmonella utilizes SopB to activate Akt, suggesting that it plays an important role in regulating host cell survival [18, 19]
Because SopB was transported to cells to play a role in mediating both actin-dependent and myosin II-dependent bacterial invasion, we attributed the induction of the first wave of Akt phosphorylation to its residual activity
Summary
Non-typhoidal salmonella (NTS) has been one of the most common foodborne zoonosis pathogens worldwide that cause host gastroenteritis. Hyperreplicating Salmonella proliferates geometrically within several hours in host cells, causing cell death and extrusion and releasing invasive bacteria into the gastrointestinal tract [11]. It is beneficial for Salmonella to prolong the lifespan of infected cells, enabling bacteria to gain sufficient time for intracellular replication. The N-terminal fragment of GSDMD accumulates on the cell membrane, forming a polymeric pore and inducing pyroptosis, which results in the release of the intracellular bacteria and inflammatory cytokines, all of which contribute to inflammation [21–23]. S. Infantis gained sufficient time to proliferate by prolonging the lifespan of infected cells, eventually causing pyroptosis, which was accompanied by the release of inflammatory factors and bacteria. Infantis gained sufficient time to proliferate by prolonging the lifespan of infected cells, eventually causing pyroptosis, which was accompanied by the release of inflammatory factors and bacteria This created favorable conditions for the spread and infection of S.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
