Subtle genetic modifications transformed an enteropathogen into a flea-borne pathogen.

Yersinia pestis is the etiological agent of plague, one of the most devastating diseases in human history. Because of the identification of the plague bacillus, the understanding of its epidemiological cycle, and the advent of efficient antibiotic therapies, the death toll due to the plague has dramatically decreased over the last 100 y. However, this disease has never been eradicated, and because of its rodent reservoir, it will not be eradicated in the near future. On the contrary, human plague cases have been reported since the 1990s in countries where the disease was thought to be extinct for decades, and therefore, the plague is now categorized as a reemerging disease. Y. pestis has two characteristics that distinguish it from most other bacterial pathogens. One is its exceptional pathogenicity for humans, with a mortality rate of 40–70% in ∼1 wk for the bubonic form and close to 100% in around 3 d for pneumonic plague. The other characteristic of Y. pestis is its transmission from rodent to rodent and from rodent to human by an infectious fleabite. These two characteristics are probably linked (see below), and therefore deciphering the mechanisms that explain the peculiar mode of transmission of Y. pestis by fleas is a key step in the understanding of pathogen evolution and gain of virulence. In PNAS, Chouikha and Hinnebusch identify a fundamental event in the adaptation of the plague bacillus to its flea vector (1). Recent Y. pestis population genetics analyses have shown that the plague bacillus emerged very recently (∼3,000 y ago) from the enteropathogen Yersinia pseudotuberculosis (2, 3). The two species are genetically almost identical, with more than 97% nucleotide identity for most of their genes (4). However, the two species have dramatically different epidemiological and pathological features. Y. pseudotuberculosis, like other pathogens of the Enterobacteriaceae family, is transmitted by the oral route and causes a usually moderate infection of the digestive tract. In contrast, Y. pestis is transmitted by fleas and may be considered as one of the most pathogenic bacteria for humans. This extreme pathogenicity and flea-borne transmission were acquired after Y. pestis diverged from its Y. pseudotuberculosis ancestor. Surprisingly, this emergence was characterized by limited gene acquisition and massive gene inactivation, with the loss of 13% of the functions of the ancestral Y. pseudotuberculosis (due to mutations, deletions, or insertions) (4). The necessity of fleas for transmission created a selective pressure that certainly had a strong impact on the pathogenicity of