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Genomic analysis of Bartonella identifies type IV secretion systems as host adaptability factors

Abstract

The bacterial genus Bartonella comprises 21 pathogens causing characteristic intraerythrocytic infections. Bartonella bacilliformis is a severe pathogen representing an ancestral lineage, whereas the other species are benign pathogens that evolved by radial speciation. Here, we have used comparative and functional genomics to infer pathogenicity genes specific to the radiating lineage, and we suggest that these genes may have facilitated adaptation to the host environment. We determined the complete genome sequence of Bartonella tribocorum by shotgun sequencing and functionally identified 97 pathogenicity genes by signature-tagged mutagenesis. Eighty-one pathogenicity genes belong to the core genome (1,097 genes) of the radiating lineage inferred from genome comparison of B. tribocorum, Bartonella henselae and Bartonella quintana. Sixty-six pathogenicity genes are present in B. bacilliformis, and one has been lost by deletion. The 14 pathogenicity genes specific for the radiating lineage encode two laterally acquired type IV secretion systems, suggesting that these systems have a role in host adaptability.

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Figure 1: Phylogenetic tree of Bartonella based on multilocus sequence analysis and summary table of the presence or absence of loci encoding the T4SSs VirB, VirB-homolog (Vbh) and Trw in the different Bartonella species.
Figure 2: Circular genome map of B. tribocorum.
Figure 3: Core genome and accessory genomes of three species of the radiating Bartonella lineage determined on the basis of ortholog gene sets (Supplementary Table 1).
Figure 4: STM mutant insertion sites in the T4SS loci virB and trw of B. tribocorum and comparison of the flanking region with B. bacilliformis.
Figure 5: Evolutionary relationship of VirB and Vbh T4SSs.
Figure 6: Comparison of the virB T4SS loci of B. henselae, B. quintana and B. tribocorum.

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Acknowledgements

We thank E.J. Rubin for providing plasmids containing the Himar1 transposon and transposase. We acknowledge the use of the MIGenAS system and excellent support by MiGenAS team members, especially M. Rampp. We thank G. Schroeder for critical reading of the manuscript. This work was supported by grant 3100A0-109925/1 from the Swiss National Science Foundation (C.D.), by grant 55005501 from the Howard Hughes Medical Institute (C.D.), by a generous donation from the Freiwillige Akademische Gesellschaft Basel (C.D.) and by the Center for Systems Bacterial Infection (C-SBI) of SystemsX, the Swiss Initiative in Systems Biology.

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Contributions

C.D., H.L.S., P.E. and S.C.S. designed the research; H.L.S., P.E., M.C.S., M.V.-T. and C.L. performed research; R.B. contributed analytical tools and materials; H.L.S., P.E., G.R., S.C.S. and C.D. analyzed data; and H.L.S., P.E. and C.D. wrote the paper.

Corresponding authors

Correspondence to Stephan C Schuster or Christoph Dehio.

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Supplementary Figure 1, Supplementary Tables 1–6, Supplementary Methods (PDF 798 kb)

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Saenz, H., Engel, P., Stoeckli, M. et al. Genomic analysis of Bartonella identifies type IV secretion systems as host adaptability factors. Nat Genet 39, 1469–1476 (2007). https://doi.org/10.1038/ng.2007.38

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