Andrew Crighton
News Editor
Kirk Hevener of the ISU Department of Biomedical and Pharmaceutical Sciences is part of a group that is working on a new way to treat Clostridium difficile, commonly called C. difficile or C. diff. Working with researchers from Texas A&M University and the University of Hawaii, Hevener is researching a new target that could change the way C. diff is treated through a $415,000 grant from the National Institute of Health.
C. diff is a bacteria that commonly causes infection of the colon and can lead to severe damage, and in some cases can even be fatal. It is also highly drug-resistant and extremely transmittable.
Hevener identified C. diff as a possible candidate for research while working with a completely different bacteria during his postdoctoral fellowship in Chicago.
Porphyromonas gingivalis is a bacteria that causes disease in the mouth.
While these two bacteria are unrelated, they have two common traits. Both are pathogenic, meaning they cause disease, and contain an enzyme called FabK.
FabK is not found in many other bacteria, so Hevener decided that C. diff would be a good candidate to extend his work in Chicago to, with FabK being the focus of his current work.
This enzyme is part of the fatty acid synthesis pathway. This creates lipids that are used to create the cell membrane, among other functions of the cell. Within C. diff, it is also is part of the mechanism that creates the bacteria’s spores. These spores are inactive forms of the bacteria and are extremely difficult to kill. They are the reason that recurrence and transmission rates are so high inside of hospitals. Hevener is studying ways this enzyme can be targeted specifically, with molecules known as inhibitors.
If he and his team can prove that FabK is targetable, it could lead to the development of new medications specific to the treatment of C. diff.
Hevener wanted to make clear that he is currently working on target validation, and not drug development. He and his team are validating that by inhibiting this enzyme, the bacteria would not be able to able to reproduce and create spores, which would then allow others to develop a medication to leverage this mechanism.
By targeting FabK specifically, Hevener’s team would create a narrow spectrum method of treatment, as opposed to the more common broad spectrum approach.
Broad spectrum antibiotics affect all bacteria, regardless if they are pathogenic or beneficial. There are many bacteria found inside of the human body that aid in different ways from digestion to preventing harmful organisms causing infection.
This narrow spectrum approach has two benefits for a medication developed using it: it does not kill helpful organisms and it helps slow the development of resistance.
Hevener explained that it is impossible to create an antibiotic that is immune to the development of resistance, but because a medication of this type would affect only C. diff, other bacteria would not develop resistance and transfer that genetic mutation to other bacteria. This would slow the progress of a medication becoming less effective or possibly obsolete over time.
