Origin of the Plague: Prospects of Ecological-Molecular-Genetic Synthesis

Abstract

Plague, which is infamous for three devastating pandemics, remains to this day one of the most dangerous human diseases. Its pathogen, the microbe Yersinia pestis, is a priority agent in the arsenal of possible bacteriological weapons, which requires increased attention to the preventive development of systems of biological (bacteriological) security. Deep knowledge of the natural processes that caused the emergence of the causative agent of plague in nature might contribute to it. In the problem of the origin of Y. pestis, there are currently two alternative approaches, molecular-genetic (MG) and ecological. MG data led to the innovative idea of the saltational transformation of a clone of the ancestral psychrophilic saprozoobiont pseudotuberculosis microbe Y. pseudotuberculosis O:1b into a population of the plague pathogen Y. pestis by means of horizontal transfer of two plague-specific virulence plasmids pFra and pPst from the external environment or from other bacteria and inactivation/deletion of genes that lost their functions in a fundamentally new habitat, the vole (Microtinae) populations in Asia. The ecological scenario is based on the Darwinian idea of the adaptogenesis of the plague microbe with the rapid “quantum” formation of its properties in the marmot- flea (Marmota sibirica and Oropsylla silantiewi) parasitic system under the conditions of the Central Asia psychroarid climate at the turn of the Pleistocene and Holocene periods. Three important factors of quantum speciation of the plague microbe were identified: marmot heterothermy during hibernation, an oxidative burst of macrophages in the body of repeatedly awakening hibernating marmots, and stress-induced muta-genesis of the evolving microbe due to the oxidative burst of macrophages. This paper argues the principle of complementarity between the environmental and MG approaches. The prospect of solving the problem of quantum speciation of the causative agent of plague and the development of tools and methods for treating and preventing this disease is seen in the synthesis of the ecological and MG approaches.