The clever Salmonella might offer clues to treating cancer
Salmonella is certainly no friend to humans. The destructive food-borne pathogen sickens tens of thousands of people and triggers countless food recalls across the country every year. But the wily bacterium is also providing interesting insight into our own defense mechanisms and the chinks in our cellular armor.
In a paper recently published in Science, Beth A. McCormick, PhD, professor of molecular genetics & microbiology, and colleagues describe how Salmonella has evolved to employ a novel tactic to weaken the human host response to infection. By attacking and prompting the release of the host’s own defense enzyme, caspase-3, Salmonella activates bacterial toxins and induces inflammation. The paper, “Salmonella Pathogenesis and Processing of Secreted Effectors by Caspase-3,” describes how this interesting finding may lead to treatments for a variety of diseases, including cancer.
Caspase-3 normally is involved in apoptosis, or programmed cell death; apoptosis is often defective in cancer cells, which enables them to survive and replicate. Thus, if Salmonella triggers caspase to promote inflammation, perhaps it can also be used to trigger caspase and promote apoptosis among targeted cancer cells.
Read a short Q&A with Dr. McCormick, prepared for Science, below, and access the full paper here.
The Oct. 15 paper was authored by McCormick and post-doctoral associates Chittur V. Srikanth, PhD, and Ana Luisa Maldonado, PhD, and laboratory assistant Zachary Demma. 
Science Q&A with Beth A. McCormick, PhD
Science: In your paper, you discovered that Salmonella co-opts a host enzyme during the early stages of infection. What makes this finding new and interesting?
McCormick: Our discovery reveals a novel tactic that the food-borne pathogen Salmonella typhimurium has evolved to attack us as people, weakening the host response to infection. In the war waged between pathogenic microorganisms and humans, the organism attacks the host and in response, the host launches a counter-attack by a defense mechanism. We have found that Salmonella re-attacks the host by altering its virulence determinants by using a host enzyme, named caspase-3. This enzyme is not only undermined by the bacterium but ends up significantly contributing to inflammation during the infection. This finding is interesting since the subversion of the host cell by Salmonella is an ingenious way to promote infection and inflammation, as the host cell is inadvertently contributing to infection. Thus, our finding uncovers a new paradigm in the field of bacterial pathogenesis and opens the door to novel investigation on other pathogenic organisms and the methods they use to make us sick.
Science: What is the take-home message from your experiment and results?
McCormick: Our work describes an exciting new mechanism by which Salmonella subverts host defense. We have discovered that Salmonella typhimurium is able to sabotage a major host death pathway, whereby the organism uses a key enzyme of this pathway to facilitate infection and pathogenesis.
Science: How do we start to apply your findings to people? That is, how can patients benefit from your findings? Might this help researchers create drugs to stop salmonella infection early on or even prevent it?
McCormick: Our findings have significant application to benefiting people and patients, which will be of high impact. We can now become very focused in limiting these pathogenic-host interactions in a very specific and directed way. For example, novel therapeutic approaches can be developed which directly target the caspase-3 motifs within the Salmonella virulence determinants, as alteration of these motifs drastically weakens the organism¹s pathogenic potential. Moreover, altering caspase-3 motifs in Salmonella virulence determinants offers new opportunities for the design of live vaccines. This approach may also be considered interesting for researchers in the veterinary and food safety sciences, because in limiting the infection of animals and food, the subsequent exposure is also reduced to humans.
