Genome Evolution and Host Adaptation in Bartonella

Sammanfattning: Bacteria of the genus Bartonella infect the red blood cells of a wide range of wild and domestic mammals and are transmitted between hosts by blood-sucking insects. Although most Bartonella infections are asymptomatic, the genus contains several human pathogens. In this work, host adaptation and host switches in Bartonella have been studied from a genomic perspective, with special focus on the acquisition and evolution of genes involved in host interactions. As part of this study, the complete genome of B. grahamii isolated from a Swedish wood mouse was sequenced. A genus-wide comparison revealed that rodent-associated Bartonella species, which have rarely been associated with human disease, have the largest genomes and the largest number of host-adaptability genes. Analysis of known and putative genes for host interactions identified several families of autotransporters as horizontally transferred to the Bartonella ancestor, with a possible role both during early host adaptation and subsequent host shifts. In B. grahamii, the association of a gene transfer agent (GTA) and phage-derived run-off replication of a large genomic segment was demonstrated for the first time. Among all acquisitions to the Bartonella ancestor, the only well conserved gene clusters are those that encode the GTA and contain the origin of the run-off replication. This conservation, along with a high density of host-adaptability genes in the amplified region suggest that the GTA provides a strong selective advantage, possibly by increasing recombination frequencies of host-adaptability genes, thereby facilitating evasion of the host immune system and colonization of new hosts. B. grahamii displays stronger geographic pattern and higher recombination frequencies than the cat-associated B. henselae, probably caused by different lifestyles and/or population sizes of the hosts. The genomic diversity of B. grahamii is markedly lower in Europe and North America than in Asia, possibly an effect of reduced host variability in these areas following the latest ice age.