Consequences of Missense Mutations in Yersinia pestis: Efficient Flow of Metabolic Carbon Versus Virulence

Abstract

Emergence of Yersinia pseudotuberculosis from Yersinia enterocolitica required about 50 million years even though both species remain robust enteropathogens capable of long-term persistence in nature. In contrast, only 20,000 years was required for Y. pseudotuberculosis to diverge into Yersinia pestis, the causative agent of bubonic plague. This brief evolutionary process entailed lateral acquisition of new virulence determinants that mediate flea-borne transmission of the most acute systemic bacterial disease known to man as well as loss of enzymes necessary for endurance in natural environments. As a consequence, numerous metabolic processes of Y. pestis are now inefficient during growth in vitro although they are obviously unimportant if not even beneficial during residence in vivo. These lesions include nutritional requirements, bioenergetics issues, regulatory parameters, and inner membrane integrity. This review addresses the question of whether or not the defects arose by random mutational loss or positive selection. Many of these events, especially those caused by missense mutations, are readily reversible thus raising the specter of an emerging variant capable of both causing plague and prolonged survival in soil and water.