Genomics of epidemic pathogens.

Virulence factors are thought to be responsible for the virulence capacity of pathogenic bacteria. However, epidemic bacteria were recently found to contain significantly fewer 'virulence factors' than non-epidemic species, and some of the most dangerous epidemic bacteria, such as Mycobacteria spp. and Rickettsia spp., have reduced genomes, and contain hundreds of degraded genes. Epidemic bacteria are actually highly specialized species, characterized by allopatric speciation, that, after adapting to their hosts, attempt to maintain a balance between gene gain and gene loss that favours gene loss, finally leading to genome reduction. Recent comparative genomic studies have demonstrated that the specialization of bacteria to eukaryotic cells is associated with massive gene loss. Furthermore, the 12 deadliest epidemic species for humankind have significantly smaller genomes, with fewer open reading frames, than less dangerous species. Epidemic species mostly lose genes related to metabolic activity, the production of energy, cell motility, and transcription. Epidemic bacteria also possess a damaged recombination and repair system and significantly more toxins than closely related non-pathogenic or non-epidemic species, and more toxin-antitoxin modules. Epidemic bacteria are therefore highly specialized species that are adapted to their hosts and characterized by extensive genome reduction. Except for toxins and toxin-antitoxin modules, which have a direct and measurable effect, other 'virulence factors' are factors associated with fitness in experimental models. Epidemic species are defined by a virulent genomic repertoire including both present and absent genes.