ggMOB-Net: Elucidation of Genomic Conjugative Features and Associated Cargo Genes across Bacterial Genera Using Genus-Genus Mobilization Networks

Gowri Nayar, Ignacio Terrizzano, Ed Seabolt, Akshay Agarwal, Christina Boucher, Jaime Ruiz, Ilya B Sizovskiy, James H Kaufman, and Noelle Noyes

Horizontal gene transfer mediated by conjugation is considered an important evolutionary mechanism of bacteria. It allows organisms to quickly evolve new phenotypic properties including antimicrobial resistance (AMR) and virulence. The frequency of conjugation-mediated cargo gene exchange has not yet been comprehensively studied within and between bacterial taxa. In this paper, we developed a frequency-based mobilization network of genus-genus conjugation features and cargo genes, using whole-genome sequence data from over 200,000 bacterial genomes, representing 1,345 genera. Our results revealed that over half of the bacterial genomes contained one or more known conjugation features that matched exactly to at least one other genome. Moreover, the proportion of genomes containing these conjugation features varied substantially by genus and conjugation feature. These results and the genus-level network structure can be viewed interactively using the ggMOB-Net tool, which allows for user-defined filtering of conjugation features and cargo genes. Using the network data, we observed that the ratio of AMR gene representation in conjugative versus non-conjugative genomes exceeded 5:1, confirming that conjugation is a critical force for AMR spread across genera. Finally, we demonstrated that clustering genomes by conjugation profile sometimes correlated well with classical phylogenetic structuring; but that in some cases the clustering was highly discordant, suggesting that the importance of the accessory genome in driving bacterial evolution may be highly variable across both time and taxonomy. These results demonstrate the utility of the ggMOB-Net tool, which can be used by researchers to further probe genus-genus mobilization dynamics. ggMOB-Net will be especially useful for generating insights into conjugative mobilization between unculturable bacteria and complex interactions involving multiple genera, as such insights are difficult to obtain experimentally.

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Highlights

We construct a frequency-based mobile network showing genus-genus conjugation features and cargo genes from >200,000 publicly available bacterial genomes, representing 1,345 different genera.
We make the resulting computational method which allows the network to be queried and visualized publicly available under the GNU v3 license: . We refer to our method as (ggMOB-Net).
We show how ggMOB-Net can be used to provide insight into conjugative mobilization between unculturable bacteria spanning multiple genera.
In particular, we observe that the ratio of AMR gene representation in conjugative versus non-conjugative genomes exceeded 5:1, confirming that conjugation is a critical force for antimicrobial resistance spread across genera.

Citation

Nayar G, Terrizzano I, Seabolt E, Agarwal A, Boucher C, Ruiz J, Slizovskiy IB, Kaufman JH and Noyes N (2022), ggMOB: Elucidation of genomic conjugative features and associated cargo genes across bacterial genera using genus-genus mobilization networks. Front. Genet. 13:1024577. doi: 10.3389/fgene.2022.1024577