Project  DEBS-Plague

The objective of this project is to investigate the biotic and abiotic determinants of the maintenance and transmission of Yersinia pestis, the etiological agent of plague, in both mainland and overseas France (La Réunion and Mayotte).

Plague is a deadly disease transmitted by rodent fleas. Although it no longer occurs in Europe, it should not be relegated to a mere historical curiosity. In fact, it is currently a major concern for France and the rest of Europe, as the plague bacterium, Yersinia pestis, could be reintroduced into our metropolitan and overseas territories. This reintroduction could occur for various reasons—natural (such as climate change), accidental (via intense global trade with plague-endemic areas), situational (such as endemic poverty and political instability), or even criminal, since Y. pestis is a formidable biological weapon that has been used multiple times in the past. Whatever the cause, if plague were to return, it would inevitably impact wildlife, our healthcare system, and our socio-economic structures (notably tourism). Moreover, in the absence of a vaccine, the situation would be significantly worsened if a multi-drug-resistant strain of the plague bacillus were to emerge, whether naturally or through militarized action. Should plague reappear, the key questions would include where, how, for how long, and why it would persist and/or spread, and what ecological and molecular means could be employed to control or even eradicate it.

To prepare for this possibility, we have, for the first time, brought together historians, archaeologists, soil scientists, biologists, mathematicians, and engineers—including French and European plague specialists—forming an international interdisciplinary consortium. Within this framework, we will implement a unique, synergistic, and holistic approach to understanding and combating plague. Together, we will analyze historical and archaeological data, compare current bacterial genomes with those from the medieval era to identify key genetic events in plague dynamics, and conduct both field research and laboratory experiments. These will, in part, rely on innovative systems that allow us to study plague dynamics and elucidate the virulence mechanisms used by Yersinia pestis to be transmitted by fleas and cause deadly infection in mammals at an unprecedented level. This will enable us to produce the first risk maps and initial insights into how French ecosystems respond to a plague outbreak, as well as identify potential intervention strategies. Beyond our specific project, our effort to structure national and international laboratories around plague research, along with our approach and data, will contribute to developing a model system applicable to other zoonotic infectious diseases—including the forthcoming Disease X, which could prove even more devastating than SARS-CoV-2.