Systemic responses of BALB/c mice to Salmonella typhimurium infection.

Salmonella typhimurium is a bacterial pathogen that poses a great threat to humans and animals. In order to discover hosts' responses to S. typhimurium infection, we collected and analyzed biofluids and organ tissues from mice which had ingested S. typhimurium. We employed (1)H NMR spectroscopy coupled with multivariate data analysis and immunological techniques. The results indicate that infection leads to a severe impact on mice spleen and ileum, which are characterized by splenomegaly and edematous villi, respectively. We found that increased levels of itaconic acid were correlated with the presence of splenomegaly during infection and may play an important role in Salmonella-containing vacuole acidification. In addition, metabonomic analyses of urine displayed the development of salmonellosis in mice, which is characterized by dynamic changes in energy metabolism. Furthermore, we found that the presence of S. typhimurium activated an anti-oxidative response in infected mice. We also observed changes in the gut microbial co-metabolites (hippurate, TMAO, TMA, methylamine). This investigation sheds much needed light on the host-pathogen interactions of S. typhimurium, providing further information to deepen our understanding of the long co-evolution process between hosts and infective bacteria.