A novel gene transfer agent from Bartonella

A gene transfer agent (GTA) that preferentially packages host adaptability genes has been discovered in the pathogenic bacterial genus Bartonella.

Bartonella are vector borne, facultative intracellular bacteria that infect erythrocytes and endothelial cells in various mammalian species. Berglund et al. sequenced the genome of the rodent infecting species Bartonella grahamii, and compared it with various other sequenced Bartonella genomes. Rodent associated Bartonella species had a larger amount of imported genes than other species. Most of these horizontally transferred genes were either bacteriophage derived, or encoded proteins involved in secretion or transport systems. A large proportion of the imported genes were located in a 461kb segment of the genome that the authors termed the chromosomal high plasticity zone.

The chromosomal high plasticity zone was present in all Bartonella species, but was most expanded in the rodent associated species. It showed similarities to auxiliary replicons (ie large extra-chromosomal elements) from related species.  Genes encoding type IV and type V secretion systems, that mediate bacterial invasion of erythrocytes and endothelial cells, were ancestrally located in the chromosomal high plasticity zone.

Bacteriophage particles were observed in Bartonella cultures. When these phage were isolated it was found that they contained proteins encoded at a cluster of phage genes in the high plasticity zone (phage cluster II), and packaged 14kb strands of DNA. By hybridisation of the phage encapsulated DNA against microarrays covering the bacterial chromosome, it was found that the phage contained DNA from the entire bacterial genome but that DNA from the high plasticity zone was overrepresented. The peak of the hybridisation signal was located at another cluster of phage genes within the high plasticity zone (phage cluster III).

It appears that auxiliary DNA replication from a phage derived origin of replication within the high plasticity zone is amplifying the Bartonella genome. The products of this ‘run-off’ replication are then being packaged into phage-like gene transfer agents. This is the first time a coupling of run-off replication and GTAs has been demonstrated. Previously discovered GTAs have packaged chromosomal DNA randomly, but in this instance the packaged DNA is biased towards DNA from the high plasticity zone, which is enriched for host adaptability genes.

The genes of the Bartonella GTA didn’t show any similarity to the RcGTA-like agents that are found in many other alpha-proteobacteria. Interestingly, Bartonella GTA-like clusters were identified in some other Rhizobiales species that also possessed RcGTA-like clusters. It would be interesting to enquire as to whether the GTAs in these species are also associated with run-off replication.

The authors suggest that the linkage of run-off replication and the GTA is selectively advantageous, in that not only is the rapid spread of new genes facilitated, but so is gene diversification by recombination.

 Berglund, E., Frank, A., Calteau, A., Vinnere Pettersson, O., Granberg, F., Eriksson, A., Näslund, K., Holmberg, M., Lindroos, H., & Andersson, S. (2009). Run-Off Replication of Host-Adaptability Genes Is Associated with Gene Transfer Agents in the Genome of Mouse-Infecting Bartonella grahamii PLoS Genetics, 5 (7) DOI: 10.1371/journal.pgen.1000546


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