Uncovering molecular pathways

You might think of tuberculosis (TB) as a disease of the past, similar to polio or smallpox. In fact, it is the world's most infectious killer, according to the World Health Organization, causing an estimated 1.5 million deaths annually. Up to one-fifth of the global population, including 13 million Americans, have TB, although most cases are in a dormant, or inactive, form.

TB is treatable with antibiotics, but up to 5% of infections are now resistant to drugs. New research by University of Delaware biology professor Karl Schmitz may provide a pathway to the development of new treatments.

Schmitz, an assistant professor in the Departments of Biological Sciences and Chemistry and Biochemistry, recently received a $1.88 million, five-year R01 grant from the National Institutes of Health (NIH) and the National Institute of Allergy and Infectious Diseases (NIAID) to map the basic biology of the bacterium that causes the disease, focusing on the specific role of unusual chemical modifications of its cellular proteins, called phosphoarginine.

These modifications can help the bacteria survive environmental stresses. Schmitz and his team are working to understand the connection between the modifications and certain enzymes they interact with that are promising targets for new antibacterial drugs.

The science

Schmitz's research lab studies protease enzymes in TB-causing bacteria. These enzymes play critical roles in bacterial physiology. Previous work by his lab found that these proteases interact with proteins carrying phosphoarginine modifications, but the significance of the interaction was unclear.

Recent work by doctoral students Henry Anderson and Pratistha Kandel suggests that phosphoarginine changes the activity of these enzymes as part of a cell-wide pathway that helps the bacteria survive environmental stresses, which may be important for infection.