Separated at Birth? Microarray Analysis of Two Strikingly Similar Yersinia Species

The Black Death is possibly the most infamous pandemic in human history, which killed onethird of the European population and subsequently shaped Western civilization (reviewed in [5]). Epidemics occurred in relentless cycles up to the seventeenth century, until severe depopulation caused a gradual decline in cases. All this was caused by a single pathological agent, the Gram-negative bacterium, Yersinia pestis. The Black Death was the second of three plague pandemics, and was thought to be caused by the Y. pestis biovar Medievalis. The first pandemic was the Justinian plague, thought to be caused by the Y. pestis biovar Antiqua, which resulted in devastation throughout the Middle East and Mediterranean basin during the sixth to eighth centuries. The final pandemic, caused by biovar Orientalis, began in 1855 in China, and killed millions of people during the nineteenth and twentieth centuries. Approximately 2000 cases are reported to the World Health Organization each year. Y. pestis is still endemic in some parts of the world, although public health measures and antibiotics have all but eliminated plague as a human disease from most developed countries. It is curious that the closest relative to Y. pestis, Yersinia pseudotuberculosis, usually causes mild gastroenteritis in humans. Despite the fact that these species cause remarkably different diseases, they are very closely related at the genetic level (99% nucleotide identity for most shared genes), and data based on multiple locus sequence typing (MLST) analysis suggests that Y. pestis diverged from Y. pseudotuberculosis only 1500–20 000 years ago [1]. Essentially, Y. pseudotuberculosis, a mild gut pathogen, has evolved into Y. pestis, which has devastated the human race, in an eye-blink of evolutionary time. The major genetic difference between the two species appears to be the acquisition of two plasmids by Y. pestis. Pathogenic Y. pseudotuberculosis retains a single plasmid (pCD1), whereas Y. pestis also retains two extra plasmids (pMT1 and pPCP1). It is therefore widely accepted that Y. pestis was once a simple enteropathogen, and acquiring these two plasmids, and other chromosomally located genes, allowed it