Insights Into The Interaction Between Yersinia Pestis And Its Host From In Vivo Transcriptional Profiling

Yersinia pestis, the etiological agent of plague, has attracted much interest recently because of its potential use as a weapon in bioterrorism. Y. pestis can induce bubonic, pneumonic and septicemic plague. Pneumonic plague is more acute than bubonic plague with higher mortality without timely effective treatment. Despite the importance of pneumonic plague caused by Yersinia pestis, little is known about the interaction between Y. pestis and its host at the molecular level during the disease development. In this study, we developed an intranasally challenged plague model in the mice and investigated the kinetics of the disease progression by pathology, transcriptional profiling of Y. pestis and host.Pathogenic bacteria have evolved complex regulatory networks to response to various environmental stresses, including entry into the host. The adaptation of gene expression in response to altered environmental cues appears to be essential for bacterial survival. In this study, the transcriptional temporal-changes of regulation network of Y. pestis (global regulator, transcriptional factor, two-component system and quorum sensing system) were measured by quantitative RT-PCR in order to explore the pathogenesis for the infection and survival in the host. Some known virulence factors were also included in the study. Microbial infection is the outcome of host-pathogen interaction. Microarray were utilized to portrait the host responses against Y. pestis during the infection. In this study, we documented the transcriptional responses of some important genes of Y. pestis and mice at different stages of plague infection, which provide a chance to assess the molecular mechanism of the disease progression, and also illustrate the pathogenesis of Y. pestis and the host defense against the plague at the transcriptional level. Our results characterized the ability how Y. pestis adapt and survive in the host, and also how the host response to the exogenous pathogen, which partly contributed to the knowledge about interaction of pathogen and host. The kinetics of transcriptional regulation of certain important genes of Y. pestis in vivo revealed how Y. pestis response to the conditions in the host, and implied the disease progression. The differential expression of mice genes at the early and terminal phase of infection also coincided with the phases of disease development. An increased transcriptional expression of Y. pestis important virulence genes and mice genes involving in defense response, immune response, inflammation response and response to stimulus, etc., present a brief overview of the interaction between Y. pestis and its host during the intranasally challenged plague progression. Meanwhile, the persisting up regulation of Y. pestis genes and global reduced gene expression of mice genes at the terminal phase demonstrated the inhibition of host immune response caused by the invasion of Y. pestis.