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!

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About ycpmicro

My name is David Singleton, and I am an Associate Professor of Microbiology at York College of Pennsylvania. My main course is BIO230, a course taken by allied-health students at YCP. Views on this site are my own.

Posted on March 15, 2012, in Bonus!, You are what you eat. Bookmark the permalink. 10 Comments.

  1. Whipple’s disease is a gastrointestinal disease caused by Tropheryma whipplei.

    • This was of course the diagnosis in House S06EP15 (prior the YCP “House Party” diagnosis recaps) and was an intermediate diagnosis in House S08EP3. The frequency at which it is bandied about on House belies its low incidence rate.

      Thank you for playing Robin! Your bag of bonus points is in the mail.

  2. Andrea Hetrick

    Crohn’s Disease is a gastrointestinal disease, that researchers believe it is caused by abnormal reaction of the body’s immune system. It interested me as i was looking up gastrointestinal diseases that most of the causes where unknown to researchers that it was really what they think they believed by supported evidence.

    • According to Pubmed Health, there is no single etiologic agent for Crohn’s Disease, and in many cases no infectious agent appears to be involved. When an abnormal reaction of the immune system to the normal microbiota is implicated, the only treatment (not a cure) is to diminish the immune response, which could lead to additional complications.

  3. Helicobactor pylori is a Gram negative microaerophilic bacteria that causes gastritis. It is also known to cause gastric ulcers, duodenal ulcers and in rare cases, stomach cancer. It is a bacteria that lives in the upper GI tract.

  4. Desiree Turpin

    Celiac Disease is a disorder of the small intestine. It is caused by a sensitivity to gluten, a protein of wheat and some other cereals. Gliadin (a component of gluten) damages the lining of the small intestine (the villi) so that it is unable to absorb nutrients into the body properly. There is no cure.

    • Like Crohn’s Disease above, this disease is not an infectious disease, but rather a response to a (presumably) environmental trigger. Let’s focus on infectious disease from now on.

  5. Tiffany Laughman

    Intestinal tuberculosis is an infectious disease caused by Mycobacterium tuberculosis which we have talked about in class

    • My quick searching suggests that GI involvement in mycobacterial infections is very rare, and I could not find an indication of how this form of it was acquired. Tuberculosis is a classically respiratory acquired disease (mainly via aerosols, or indirectly via air currents), which sets up with primary pulmonary involvement. It can however persist in the body, particularly in individuals who are immunocompromised, and later disseminate to other body sites. This is what I suspect is happening in intestinal tuberculosis, with the initial portal of entry via the respiratory system, and later dissemination to the GI tract.

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