Comparative Approaches to Identify Host Factors Specifically Targeted by Yersinia pestis During the Infectious Process

Abstract

The genus Yersinia includes three species pathogenic for humans and animals: Y. enterocolitica, Y. pseudotuberculosis and Y. pestis. The two former species behave like true enteropathogens, i.e. they cause mild intestinal symptoms and are transmitted by the fecal-oral route. In contrast, Y. pestis is the etiologic agent of plague, a highly severe and often fatal disease, which is transmitted by flea bites (bubonic plague) or aerosols (pneumonic plague). The plague bacillus is one of the most pathogenic microorganisms of the bacterial kingdom, but the mechanisms it specifically uses to kill its host so efficiently remain largely unknown. Despite drastically different clinical and epidemiological features between enteropathogenic Yersinia and the plague agent, it appears that Y. pestis is a clone recently emerged from Y. pseudotuberculosis (less than 20,000 years ago). Genome comparison indicates that the two species are genetically highly similar. This close genetic relationship is used to carry out comparative pathophysiological studies between Y. pestis and its recent ancestor Y. pseudotuberculosis, in an attempt to identify the host factors and/or cell lineages specifically targeted by the plague bacillus during the infectious process. Another comparative approach based on the identification of genetic and physiological differences between mouse strains that are either resistant or susceptible to plague is another mean to identify host responses specifically diverted by the plague bacillus.