How Plague-Causing Bacteria Disarm Host Defense

Effector proteins are the bad guys that help bacterial pathogens do their job of infecting the host by crippling the body’s immune system. In essence, they knock down the front door of resistance and disarm the cell’s alarm system.

Now, researchers at the University of California, San Diego (UCSD) School of Medicine have identified a novel molecular target for an effector protein called YpkA, one of several effectors of the bacteria Yersinia – the pathogen responsible for the Middle Ages’ “Black Death” and a virulent form of food poisoning today. Their study will be published online in the May 25 issue of Molecular Cell.

YpkA targets a host protein called Gáq, the messenger that transmits extracellular signals (“we are under attack!”) into the host cell, so that it can mount a defense.

“The alarm signal sent by Gáq is intercepted by YpkA, which sets up a roadblock along several cellular pathways that Gáq uses to deliver the alarm,” said lead author Lorena Navarro, Ph.D., post-doctoral researcher in the lab of the study’s principle investigator, Jack E. Dixon, Ph.D., professor of Pharmacology and Cellular and Molecular Medicine at the UCSD School of Medicine.

Identifying this new target is the first step to developing effective strategies for preventing disease, including means to fight antibiotic-resistant strains of Yersinia that could be used in biological warfare, according to Navarro.

The genus Yersinia includes three species of bacteria that are pathogenic to humans: Y. pestis is perhaps the most infamous, being responsible for the bubonic plague (also known as the Black Death), which killed more than 200 million people in the Middle Ages.