Salmonella enterica serovar Typhimurium sseK3 induces apoptosis and enhances glycolysis in macrophages

Abstract

Background: Salmonella enterica serovar Typhimurium (S. Typhimurium) is an important infectious disease pathogen that can survive and replicate in macrophages. Glycolysis is essential for immune responses against S. Typhimurium infection in macrophages, and is also associated with apoptosis. S. Typhimurium secreted effector K3 (SseK3) was recently identified as a novel translated and secreted protein. However, there is no study about the role of sseK3 in the relationship between apoptosis and glycolysis in cells infected with S. Typhimurium. It is unclear whether this protein exerts a significant role in the progress of apoptosis and glycolysis in S. Typhimurium-infected macrophages. Results: Macrophages were infected with S. Typhimurium SL1344 wild-type (WT), ΔsseK3 mutant or sseK3complemented strain, and the effects of sseK3 on apoptosis and glycolysis were determined. The adherence and invasion in the ΔsseK3 mutant group were similar to that in the WT and sseK3-complemented groups, indicating that SseK3 was not essential for the adherence and invasion of S. Typhimurium in macrophages. However, the percentage of apoptosis in the ΔsseK3 mutant group was much lower than that in the WT and sseK3complemented groups. Caspase-3, caspase-8, and caspase-9 enzyme activity in the ΔsseK3 mutant group were significantly lower than in the WT group and sseK3-complemented groups, indicating that sseK3 could improve the caspase-3, caspase-8, and caspase-9 enzyme activity. We also found that there were no significant differences in pyruvic acid levels between the three groups, but the lactic acid level in the ΔsseK3 mutant group was much lower than that in the WT and sseK3-complemented groups. The ATP levels in the ΔsseK3 mutant group were remarkably higher than those in the WT and sseK3-complemented groups. These indicated that the sseK3 enhanced the level of glycolysis in macrophages infected by S. Typhimurium. Conclusions: S. Typhimurium sseK3 is likely involved in promoting macrophage apoptosis and modulating glycolysis in macrophages. Our results could improve our understanding of the relationship between apoptosis and glycolysis in macrophages induced by S. Typhimurium sseK3.

Salmonella enterica Serovar Typhi Induces Host Metabolic Reprogramming to Increase Glucose Availability for Intracellular Replication

“…Enhanced glucose uptake and glycolysis were also detected in murine macrophages infected by the closely related serovar, S. Typhimurium, but different metabolic features were also observed [ 22 , 37 , 38 ]. Although lactate content is increased in both S. Typhimurium-infected murine macrophages and in S. Typhi-infected human macrophages, an increase in 3PG levels occurs only in the former, while an increase in glucose levels only occurs in the latter.…”

3‑Bromopyruvic acid regulates glucose metabolism by targeting the c‑Myc/TXNIP axis and induces mitochondria‑mediated apoptosis in TNBC cells

“…Thereby, Cyt-C activates caspase-3/caspase-9 and initiates a caspase signaling cascade and induces apoptosis ( 59 , 60 ). The relationship between glycolysis and apoptosis was studied by a team ( 61 ), but the conclusions had some limitations, showing that related research needs to be further carried out. In the present study, apoptosis was closely related to glycolytic enzyme inhibition.…”

Identification of a Host-Targeted Compound to Control Typhoid Fever

“…Salmonella spp. have evolved multiple mechanisms to counteract and exploit host immune pathways to evade killing, subsequently inducing cell death ( 10 , 32 – 36 ) and the induction of the inflammatory response to promote disease ( 11 ). Thus, drugs that prevent Salmonella -induced cell death could be used as a therapy to control typhoid fever.…”