From Mild to Murderous: How Yersinia pestis Evolved to Cause Pneumonic Plague

How do new pathogens emerge, and how do these pathogens take advantage of host processes and pathways to cause disease? Yersinia pestis, the etiological agent of plague, is a recently emerged clone of the gastrointestinal pathogen Y. pseudotuberculosis, but the specific genetic changes that enabled Yersinia to cause the respiratory disease known as pneumonic plague are not well understood. By using a mouse model of respiratory infection combined with comparative genetic and genomic studies between Yersinia species, we have identified two specific events – the acquisition of the Pla protease and the inactivation of the YadA adhesin – as key steps in the emergence of Y. pestis as an easily transmissible, severe respiratory pathogen. The acquisition of the Pla protease enabled emergent, ancestral Y. pestis strains to grow to high levels in the lungs and cause a fulminant, multifocal severe pneumonia, while the loss of YadA shifted the respiratory infection from a restricted, granuloma-like pathology to a loosely contained, easily expelled state. Indeed, the loss of YadA by Y. pseudotuberculosis may have been a key step by which Y. pestis acquired the ability to be spread by respiratory droplets, thus enabling epidemics of pneumonic plague. Author - Dr. Lathem, Wyndham, Northwestern University, Chicago, United States of America (Presenting author) Co-author(s) - Zimbler, Daniel, Northwestern University, Chicago, United States of America Co-author(s) - Eddy, Justin, Northwestern University, Chicago, United States of America Co-author(s) - Schroeder, Jay, Northwestern University, Chicago, United States of America Co-author(s) - Ritzert, Jeremy, Northwestern University, Chicago, United States of America