The invasive pathogen Yersinia pestis disrupts host blood vasculature to spread and provoke hemorrhages

Yersinia pestis is a powerful pathogen with a rare invasive capacity. After a flea bite, the plague bacillus can reach the bloodstream in a matter of days giving way to invade the whole organism reaching all organs and provoking disseminated hemorrhages. However, the mechanisms used by this bacterium to cross and disrupt the endothelial vascular barrier remain poorly understood. In this study, an innovative model of in vivo infection was used to focus on the interaction between Y. pestis and its host vascular system. In the draining lymph nodes and in secondary organs, bacteria provoked the porosity and disruption of blood vessels. An in vitro model of endothelial barrier showed a role in this phenotype for the pYV/pCD1 plasmid that carries a Type Three Secretion System. This work supports that the pYV/pCD1 plasmid is responsible for the powerful tissue invasiveness capacity of the plague bacillus and the hemorrhagic features of plague.
Author summary The plague bacillus, Yersinia pestis, is a powerful pathogen with a rare invasive capacity and is among the few bacteria capable to provoke disseminated hemorrhages. However, the mechanisms used by this bacterium to cross and disrupt the endothelial vascular barrier remain poorly understood. Recent technical progress in microscopy, associated with the use of original fluorescent mutant in mice, allowed us to develop an innovative model of infection in vivo. This model permitted to look directly into the interaction between Y. pestis and its host vascular system, in 3D reconstructed tissues without physical alteration. We were able to observe the degradation of blood vessels in the draining lymph nodes and to visualize the spreading of the bacteria into secondary organs directly through the vascular barrier. Classical in vitro experiments validated the in vivo observation and demonstrated the role of some of the bacterial components in this phenotype. This work shows an unprecedented visualization of the pathogenesis of Y. pestis and decipher part of the powerful invasiveness capacity of the plague bacillus and the hemorrhagic features of plague.