E. Coli and the Innate Immune System: Sources for Future Therapeutics

>>Often the key to any victory is to understand
fully your opponent. This is especially true when that opponent is a significant food-borne
bacterial pathogen such as E. coli O157:H7. Dr. Philip Hardwidge, associate professor
in Diagnostic Medicine/Pathobiology, and his lab are seeking to understand fully how pathogens
such as E. coli use proteins to block a host’s innate immune system. This system is the body’s
first defense against infection, often presented in the body’s mucosal surfaces such as those
found in the intestine.>>DR. PHILIP HARDWIDGE: In terms of infectious
disease, this inhibition of the human innate immune response is absolutely critical for
the bacterium’s ability to cause an infection, so if we can identify choke points in the
interaction between the bacterium and the host, we may be able to inhibit the bacterium
and prevent its survival in an infected human being.>>Dr. Hardwidge’s lab is currently participating
in a National Institutes of Health grant to explore a protein expressed by pathogenic
E. Coli known as NleH1, which inhibits an important cellular signaling pathway called
IKK/NF-B (I-Kappa-Kinase/N-F-Kappa-B).>>DR. PHILIP HARDWIDGE: This protein is one
example of an injected bacterial protein that is able to block the innate immune system
. . . so this protein has kind of an unusual mechanism that had not been seen in other
bacterial or viral pathogens so we’re interested in understanding more about how this protein
really works and whether it might represent a good target for future therapeutics.>>The exploration of these host/pathogen
interactions requires the lab to use multi-disciplinary approaches including using animal models and
advanced technologies such as quantitative PCR.>>MIKE HAYS: One of beauties of QPCR, or
Quantitative PCR, is that it gives a really reliable and easily to define comparative
number of gene expression. It looks at a snapshot in time in that cellular environment and it
could tell us at that snapshot in time, in that window, what the expression levels are
of the genes that we’re interested in.>>Understanding how these bacterial proteins
function in the host/pathogen interaction may also have exciting applications for other
human diseases.>>DR. PHILIP HARDWIDGE: For example, many
auto immune diseases, many cancers and even diabetes are caused in part by an overactive
component of this innate immune system, so using information from bacteria and viruses
that have evolved to block this overactive immune response, we may be able to engineer
some of these bacteria proteins as potential therapeutics.>>Through collaborations at K-State and his
position as a Chinese Academy of Sciences’ Senior International Scientist, Dr. Hardwidge’s
future research will also explore both the role that the microbes that naturally live
in the human body have in host/pathogen interactions and other forms of E. Coli that afflict humans.
Armed with this knowledge, researchers at the Kansas State University College of Veterinary
Medicine will be able to reveal new strategies for defeating pathogens such as E. coli O157:H7.