Evolution of bacterial pathogens

Several bacteria that are part of the Rickettsiales group are causative agents in human diseases such as typhus and ehrlichiosis. Understanding the evolutionary transition of such human pathogens from free-living bacterium could help us combat such diseases more effectively. With this in mind, the RICKOCHET (Origin and evolution of host-association and pathogenicity in the Rickettsiales) project was initiated.

RICKOCHET obtained genomic material from alphaproteobacterial lineages such as the endosymbiotic lineages, C36 and EI3 as well as three individual alphaproteobacterial cells. O14 and N20 were isolated from oceanic waters in USA and the L4 cell was isolated from lake water. Project members used next-generation sequencing and single cell genomics to gain insight into the origin and evolution of different Rickettsiales species and lineages.

To begin with, researchers prepared sequence libraries and assembled sequence data. As a result, they obtained near-complete genomes of C36 and EI3. For the aquatic single cells (N20, O14 and L4), they managed to get partial genomes.

Several significant insights were obtained. Analyses of C36 and EI3 revealed that they contained several genes involved in host-interaction processes in common with the human pathogens that are part of Rickettsiales. Results suggest that interaction with amoebae (in this case - the host of C36 and EI3), facilitated the evolution of intracellular bacterial pathogens. These results were published in two papers.

Analysis of 50 % of the L4 genome uncovered the fact that it is a deeply branching lineage of the Rickettsiaceae. It has both flagellar as well as parasitic lifestyle genes. A missing link in the emergence of the Rickettsiaceae, further analysis of this lineage should provide novel insight.

Though the O14 and N20 genomes are part of the alphaproteobacterial clade like the Rickettsiales, they do not show any signs of intracellular lifestyle. Further comparative analyses should shed light on factors contributing to the emergence of intracellular lifestyle in Rickettsiales.

RICKOCHET findings have laid the ground for further research into genetic changes that facilitate pathogenicity in microbes. Applications include drug design, vaccine development and microbial engineering.