Credit: Jamey Marth
Recurrent previous Infections by Salmonella disrupt the body's normal protection against toxic components of resident colonic bacteria. The anti-inflammatory enzyme Intestinal Alkaline Phosphatase (IAP) is produced in the small intestine (dark blue), where it is released into the lumen and flows into the colon. IAP concentrations in the colon are normally sufficient to de-phosphorylate and thereby detoxify lipopolysaccharide (LPS-P) produced by commensal and resident colonic bacteria (left panel). Previous and repeated Salmonella infections induce neuraminidase (Neu) activity in the small intestine, thereby accelerating the molecular aging and turnover of IAP. This reduces IAP production, resulting in IAP concentrations that are below normal (right panel). Increased levels of pro-inflammatory LPS-phosphate (LPS-P) due to IAP deficiency cause a progressive and persistent colitis. Phosphate (P) is represented by yellow circles.