Immune system evasion by Salmonella
Salmonellosis is a gastrointestinally acquired infection that currently affects around 40,000 people annually in the United States. Because the disease may be mild, the actual rate of infection is likely significantly higher. A recent summary in Science Daily describes recently published research from the University of California that examined how Salmonella enterica is able to evade our immune system, and continue living in the human digestive tract.
Although the lower digestive tract has a complex population of microorganism under normal circumstances, potent immune system effectors work to prevent the penetration of these bacteria into the tissues of the colon where they might be able to cause disease. One important aspect of our defenses is the action of phagocytic immune cells, which migrate through the tissues of the digestive tract looking for and eliminating pathogenic microorganisms. Neutrophils (one of these phagocytic cells) can operate and inhibit microbial growth by actively reducing the amount of essential nutrients that might be available for microbial growth. For example, neutrophils can secrete the protein calprotectin, a protein that binds to and sequesters the element zinc, which in turn is an essential trace element necessary for microbial growth. In the absence of usable levels of zinc, microorganisms would be unable to survive in this environment.
This current research looks at the ability that some strains of Salmonella have acquired that let them deal with this “nutrient warfare” carried out by the host defenses. The bacterium appear to be able to over express certain membrane transporters that help it to steal zinc away from our cells, despite the presence of calprotectin made by neutrophils. In fact, they have found that the production of calprotectin actually promotes or helps the Salmonella to grow, as the calprotectin ends up killing other microorganisms that would ordinarily be competing for nutrients with the pathogenic bacteria. We have to some extent a situation similar to the one we discussed in class recently, where we looked at how C. difficile is able to expand in numbers and cause disease when the normal microbial gut flora is eliminated through antibiotic use.
The authors go on to examine how the ability of Salmonella to acquire zinc might affect our ability to treat disease caused by this organism. A functioning inflammatory response which involves the movement of cells such as neutrophils into the tissues of the digestive tract is important in our ability to fend off infections by this organism, so any therapies which work to mediate or diminish an inflammatory response are actually counterproductive to helping a patient resolve a Salmonella infection. Instead, novel therapies which work to affect metal acquisition or adsorption might have a more profound effect, and also could be important for potentially treating other diseases such as inflammatory bowel syndrome, where high levels of calprotectin are frequently observed.
I am getting a bit distressed by the rapidly falling numbers of hits to the blog this semester by the BIO230 students, and there are still about another 7 weeks left in the term. In order to promote a quick spike in the traffic, and to hopefully promote some more interaction in this forum, here is a bonus opportunity: in the comment thread below, name a gastrointestinally acquired disease with its etiologic agent. No repeats allow (READ WHAT OTHER PEOPLE HAVE POSTED!), all submission must be received by Noon Friday March 23, 2012 for credit, and one submission per person. Bonus credit will be acknowledged on Blackboard, in the special category “Bonus Points.”
Please note that participation in this thread will permit you to submit a “Microbes in the News” summary for inclusion on the blog for further bonus points!