Abstract
Salmonella effectors translocated into epithelial cells contribute to the pathogenesis of infection. They mediate epithelial cell invasion and subsequent intracellular replication. However, their functions in vivo have not been well-identified. In this study, we uncovered a role for Salmonella outer protein B (SopB) in modulating necroptosis to facilitate bacteria escape epithelial cell and spread to systemic sites through a Salmonella-induced colitis model. Mice infected with SopB deleted strain ΔsopB displayed increased severity to colitis, reduced mucin expression and increased bacterial translocation. In vitro study, we found there was an increased goblet cell necroptosis following ΔsopB infection. Consistently, mice infected with ΔsopB had a strong upregulation of mixed lineage kinase domain-like (MLKL) phosphorylation. Deletion of MLKL rescued severity of tissue inflammatory, improved mucin2 expression and abolished the increased bacterial translocation in mice infected with ΔsopB. Intriguingly, the expression of sopB in LS174T cells was downregulated. The temporally regulated SopB expression potentially switched the role from epithelial cell invasion to bacterial transmission. Collectively, these results indicated a role for SopB in modulating the onset of necroptosis to increased bacteria pathogenesis and translocated to systemic sites.
Highlights
Salmonella enterica is a leading cause of enteric disease in human and animals that is capable of causing a wide range of illnesses ranging from a localized gastroenteritis and lymphadenitis resulting in diarrhea to life-threatening systemic infections (Kirk et al, 2015)
We initially examined the susceptibility to colitis following the oral administration of 5 × 107 colony-forming units (CFU) of Salmonella strain SL1344 or Salmonella outer protein B (SopB) mutant strain sopB
We investigated the severity to colitis following SL1344 or sopB infection. sopB infection increased goblet cell necroptosis associated with enhanced intestinal inflammation and increased bacterial translocation
Summary
Salmonella enterica is a leading cause of enteric disease in human and animals that is capable of causing a wide range of illnesses ranging from a localized gastroenteritis and lymphadenitis resulting in diarrhea to life-threatening systemic infections (Kirk et al, 2015). SPI-1 is essential for invasion of non-phagocytic cells and responsible for inflammation in Salmonella induced colitis, whereas SPI-2 is required for intracellular survival and proliferation in phagocytes, and is important in systemic infection (Barthel et al, 2003; Abrahams and Hensel, 2006) Both SPI-1 and SPI-2 encode separated type III secretion systems (T3SSs) that direct the translocation of virulence proteins into host environment (Galan, 2001; Schmidt and Hensel, 2004). These effector proteins modulate host cell immunity and are important for bacterial pathogenesis
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.
