Why Typhoid Fever Is Human Specific: Dr. Ajit Varki and Coworkers Discover One Explanation

Typhoid Mary, Not Typhoid Mouse: Lack of enzyme explains why typhoid fever is a human-specific disease

The bacterium Salmonella Typhi causes typhoid fever in humans, but leaves other mammals unaffected.  Researchers at University of California, San Diego and Yale University Schools of Medicine now offer one explanation — CMAH, an enzyme that humans lack. Without this enzyme, a toxin deployed by the bacteria is much better able to bind and enter human cells, making us sick. The study is published in the Dec. 4 issue of Cell.

In most mammals (including our closest evolutionary cousins, the great apes), the CMAH enzyme reconfigures the sugar molecules found on these animals’ cell surfaces into a form that the typhoid toxin cannot bind. Humans don’t produce CMAH, meaning our cell surface sugars are left unchanged — and as this study shows, in a state just right for typhoid toxin attachment.

“We started this project looking at something completely different in relation to cancer, but serendipity instead helped us solve the mystery of what the typhoid toxin binds,” said co-senior author Ajit Varki, MD, Distinguished Professor in the Departments of Medicine and Cellular and Molecular Medicine at UC San Diego. “That’s the beauty of basic research — though we didn’t set out with the intent, these findings may now spur the development of new therapies for typhoid fever.” Varki co-directed the study with Jorge E. Galán, PhD, DVM, professor and department chair at Yale University School of Medicine. … Read the full story from the UC San Diego Newsroom