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cgMLST - Genome-wide gene by gene microbial typing

Figure 1. MLST of 6 genes versus genome-wide cgMLST. Shown are the six N. meningitidis MLST loci and red dots across the genome that represent symbolically the cgMLST loci.

"Bacterial epidemiological typing generates isolate-specific geno- or phenotypic characters that can be used to elucidate the sources and routes of spread of bacteria. Typing may also be used to identify emerging pathogenic strains or clones within a species, including potential agents of bioterrorism" (cited from: CMI 2007, 13:Suppl 3:1 [PubMed]).

With fast and affordable microbial whole genome shotgun sequencing (WGS) and automatized software analysis (Fig. 1), microbiologists can use genome-wide gene-by-gene allele calling of hundreds/thousands of genes (core genome MLST [cgMLST]) for genotyping. cgMLST schemes consist of a fixed set of conserved genome-wide genes. Alleles are used instead of single nucleotide polymorphisms (SNP) or concatenated sequences to mitigate the effects of recombination and to enable for a global and public nomenclature (cgMLST.org Nomenclature Server). The high discriminatory power of cgMLST, coupled with rapid and simple WGS workflow, makes this complete solution ideal for everyday usage in a routine laboratory, e.g., for prospective surveillance of multi- drug resistant bacteria in a hospital (JCM 54: 2874, 2016). That is, one disruptive, accurate, and highly reproducible technology (JCM 55: 908, 2017) that fits any bacteria, any research topic, and any lab is finally within reach for every microbiologist.


The figure below illustrates how in future a hierarchical microbial WGS typing pyramid from bottom to top with increasing discriminatory power might look like. The species-specific multi locus sequence typing (MLST) will remain the basis for backwards compatibility reasons (PNAS 1998, 95:3140 [PubMed]). MLST sequence types (ST) can be easily extracted from NGS data. With appropriate software the ribosomal MLST with one pan-bacterial scheme might play in future a more prominent role (Microbiology 2012 158:1005 [PubMed]). Genome-wide gene by gene bacterial typing, i.e. cgMLST is an obvious extension of the traditional MLST concept (e.g., PLoS One 2011, 6:e22751 [PubMed] and Nature Rev. Microbiol. 2013, 11:728 [PubMed]). All three methods can be standardized in contrast to lineage-specific schemes based on explorative single nucleotide polymorphisms (SNPs; e.g., NEJM 2012, 366:2267 [PubMed]) or accessory gene alleles of the species reference genome or the species pan-genome (whole genome MLST [wgMLST]). Lineage-specific SNP or accessory gene allele approaches can be always layered on top of the standardized cgMLST schemes for 'ad hoc' analysis to gain even more discriminatory power.

Typing Pyramid Figure 2. Standardized hierarchical microbial WGS typing approach. From bottom to top with increasing discriminatory power. MLST, multi locus sequence typing; rMLST, ribosomal MLST; cgMLST, core genome MLST; wgMLST, whole genome MLST, and SNP, single nucleotide polymorphism.

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