VBI researchers in collaboration with scientists from the University of Maryland School of Medicine have created a new classification system for rickettsia bacteria that may assist researchers in the way they approach the development of diagnostics and vaccines for the virulent rickettsial pathogens. The work has been carried out as part of the PathoSystems Resource Integration Center (PATRIC) project which is led by Dr. Bruno Sobral and Dr. Joæpound;o Setubal from the Virginia Bioinformatics Institute.
Some species of Rickettsia are known to cause harmful diseases in humans, such as epidemic typhus (R. prowazekii) and Rocky Mountain spotted fever (R. rickettsii), while others have been identified as emerging pathogens and critical agents for the development of bioweapons. The Rickettsia felis bacterium has in some cases been linked to the onset of typhus-like disease in humans. Until now, it has been difficult to fit R. felis into the evolutionary picture of the rickettsia in part due to the presence of a "hard to classify" plasmid or gene-carrying element not found in the other rickettsiae.
Dr. Joseph Gillespie, a bioinformatician at the Virginia Bioinformatics Institute and the lead author of the paper, remarked: "By comparing sequences and using bioinformatic tools, we have been able to demonstrate that there is indeed strong support for the presence of a single plasmid in R. felis, and that many of the plasmid genes have probably been horizontally inherited from exchanges with other organisms. We have also been able to go one step further and show that the primitive rickettsial ancestor itself likely harbored plasmids of this type which has important implications for the evolutionary origin of the group."
The traditional rickettsial classification system divides members of the genus into three categories - spotted fever group, typhus group, and ancestral group. However, the genome sequence of R. felis shows inconsistencies that could place it in either the spotted fever or typhus groups. The new classification system highlighted in the study includes the addition of a fourth lineage—transitional group rickettsia—that provides a framework to support some of the known evolutionary relationships of these diverse bacteria. Specifically, the results offer insight into the evolution of a plastic plasmid system in rickettsiae, which includes the role plasmids may have played in the acquirement of virulence traits in pathogenic strains, and the likely origin of plasmids within the rickettsial evolutionary tree.
VBI Director and PATRIC Principal Investigator Bruno Sobral remarked: "The role plasmids play in host colonization and virulence is not well understood, and will likely only become more apparent with the discovery of plasmids in other rickettsiae. We hope that an evolutionary perspective coupled with the characterization of the contributions of these plasmids to host recognition, invasion and pathogenicity will open up exciting new research opportunities for the virulent rickettsiae. One of the goals of the PATRIC project is to enable the future development of much needed diagnostics and vaccines for a wide range of diseases. The research described in this study is a good example of how developments in evolutionary classification, for example, can help facilitate the objectives of the PATRIC project."
Public Library of Science. March 2007.