Two consecutive stages of complete isolation were identified in the speciation of the plague-causing bacterium Yersinia pestis: (1) primary spatial ecological isolation was responsible for one-way migration of bacterial cells from the ancestor Yersinia pseudotuberculosis O:1b population into a transitional recurring pseudopopulation (group, clone), which gave rise to the new Yersinia pestis species in the host-parasite system of the Mongolian tarbagan marmot (Marmota sibirica) and the Oropsylla silantiewi flea; (2) pesticin synthesis and antagonistic pleiotropy effects resulted in genetic and biochemical isolation within the transient population. These two stages of complete isolation had a macroevolutionary effect: the formerly saprozoonotic microbe adopted a new lifestyle (adaptive zone) of an obligate blood parasite transmitted by fleas. Three further stages of intraspecies isolation included (1) isolation in the course of natural Yersinia pestis spread from Mongolian tarbagan marmot populations into other Asian populations of rodents and pikas, (2) isolation in the course of worldwide expansion of the plague agent during pandemics with subsequent formation of synanthropic (rat) foci, and (3) isolation in secondary natural plague foci derived from synanthropic rat foci in Africa and Americas. The last three stages of incomplete isolation had a microevolutionary effect of intraspeci? cradiation into different rodent (pika)-flea host-parasite systems.