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MLST revisited: the genebygene approach to bacterial genomics
Martin C.J.Maiden, Melissa J.Jansen van Rensburg, James E.Bray, Sarah G.Earle, Suzanne A.Ford, Keith A.Jolley and Noel D.McCarthy
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.
Advances in nucleotide-sequencing technology have provided unparalleled accessto the enormous genetic diversity that has accumulated in the bacterial domain during 3.54billion years of evolution1. Numerous sets of whole-genome sequencing (WGS) data for bacterial isolates (BOX1) are available2, and metagenomic studies using these technologies continue to reveal further, seemingly boundless, diversity in bacterial communities3. Faced with this plethora of information, microbiologists must develop structured means of describing this diversity and of linking phenotype and genotype, thereby facilitating an improved understanding of the microbiological world. Given that we have precise information on the function of only a very small proportion of bacterial genes, and no knowledge at all about most, this is a formidable, if extremely exciting, challenge.
Here, we focus primarily on pathogenic bacteria, although the concepts discussed are applicable more widely to all bacteria and archaea. Bacterial pathogens played a crucial part in the development of experimental microbiology and remain the most intensively studied prokaryotes more than 100years later4. Pathogens have emerged across the diversity of the bacterial but, interestingly, not the archaeal domain on many occasions and are both poly
phyletic and highly diverse. Thus, although pathogens represent only a tiny subset of the bacterial world, the challenges faced by the clinical microbiology laboratory are representative of those faced by microbiology as awhole.
Taxonomic and functional analyses are based on the observations that diversity among bacteria is...