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MLST revisited: the gene-by-gene approach to bacterial genomics

Abstract

Multilocus sequence typing (MLST) was proposed in 1998 as a portable sequence-based method for identifying clonal relationships among bacteria. Today, in the whole-genome era of microbiology, the need for systematic, standardized descriptions of bacterial genotypic variation remains a priority. Here, to meet this need, we draw on the successes of MLST and 16S rRNA gene sequencing to propose a hierarchical gene-by-gene approach that reflects functional and evolutionary relationships and catalogues bacteria 'from domain to strain'. Our gene-based typing approach using online platforms such as the Bacterial Isolate Genome Sequence Database (BIGSdb) allows the scalable organization and analysis of whole-genome sequence data.

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Figure 1: Schematic illustration of the gene-by-gene approach to the analysis of genome sequences using the Bacterial Isolate Genome Sequence Database platform.
Figure 2: Relating sequence data to nomenclature schemes.
Figure 3: Ribosomal multilocus sequence typing-based analysis of Staphylococcus spp. whole-genome sequence data.

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Acknowledgements

The authors acknowledge the IMG, GenBank and SRA databases, isolates from which were included in the analyses presented in this article. All isolate genomes can be accessed at the rMLST database on PubMLST and are identified under the project names Maiden 2013 Nat Rev SCBU for the outbreak analysis, Maiden 2013 Nat Rev S aureus for the other S. aureus analyses and Maiden 2013 Nat Rev rMLST for the genus Staphylococcus rMLST analysis, with original database accession numbers provided as available. The authors are grateful to J. S. Bennett, H. B. Bratcher, C. Brehony, A. J. Cody, F. Colles, O. B. Harrison, D. M. Hill, S. K. Sheppard, E. R. Watkins and H. Wimalarathna, as well as many other collaborators, for their contributions to the development of the context of this work and for comments on the manuscript. M.C.J.M. is a Wellcome Trust Senior Fellow in Basic Biomedical Sciences. M.J.J.v.R. is funded by the Clarendon Fund and Merton College, Oxford University, UK, and J.E.B. is funded by the Patho-NGen-Trace consortium. The research from the Patho-NGen-Trace project leading to these results has received funding from the European Community's Seventh Framework Programme (FP7/2007-2013; grant 278864).

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staphylococcal rMLST analysis (PDF 391 kb)

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238 isolates with unique rSTs derived from 699 S. aureus isolates included in species level rMLST analysis (PDF 1830 kb)

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S. aureus isolates from an outbreak in a UK Special Care Baby Unit (PDF 475 kb)

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Maiden, M., van Rensburg, M., Bray, J. et al. MLST revisited: the gene-by-gene approach to bacterial genomics. Nat Rev Microbiol 11, 728–736 (2013). https://doi.org/10.1038/nrmicro3093

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