Rickettsial genomics and the paradigm of genome reduction associated with increased virulence.

Rickettsia species are arthropod endosymbiotic α-proteobacteria that can infect mammalian hosts during their obligate intracellular lifecycle, and cause a range of mild to severe diseases in humans. Paradoxically, during their adaptation to a bottleneck lifestyle, rickettsial genomes have undergone an evolution marked by a progressive chromosomic and plasmidic degradation resulting in a genome reduction from 1.5 to 1.1 Mb, with a coding capacity of 69-84%. A striking finding of rickettsial genomics has been that the most virulent species had genomes that were drastically reduced and degraded when compared to closely related less virulent or nonpathogenic species. This paradoxical evolution, which is not unique to members of the genus Rickettsia but has been identified as a convergent evolution of several major human pathogenic bacteria, parallels a selected loss of genes associated with transcriptional regulators, but with a high preservation of toxin-antitoxin (TA) modules and recombination and DNA repair proteins. In addition, these bacteria have undergone a proliferation of genetic elements, notably short palindromic elements, whose role remains unknown. Recent proteomic and transcriptomics analyses have revealed a differential level or degradation of gene expression that may, at least partially, explain differences in virulence among Rickettsia species. However, future investigations are mandatory to provide novel insights into the mechanisms by which genomic reductive evolution contributes to an emergence of pathogenesis.