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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 next generation sequencing and automatized software analysis, microbiologists can use genome-wide hundreds/thousands of genes (core genome MLST, cgMLST) for typing (Fig. 1), resulting in higher discrimination and more accurate strain typing. cgMLST schemes consist of a fixed set of conserved genome-wide genes for each species or group of closely related species. Thereby cgMLST is ideally suited to standardize whole genome sequencing (WGS) based bacterial genotyping (cgMLST.org Nomenclature Server) The heightened discrimination power of cgMLST, coupled with rapid and simple workflow next generation sequencing (NGS), makes this complete solution ideal for everyday microbial monitoring to outbreak investigation (e.g., MtbC JCM 2014, 52:2479 [PubMed], MRSA JCM 2014, 52:2365 [PubMed] & Listeria JCM 2015, 53:2869 [PubMed]). 2013/2014 the U.S. Centers for Disease Control and Prevention (CDC) adopted and is currently implementing the cgMLST approach for its PulseNet USA and PulseNet International networks (Clin Infect Dis. 2016, 62:380 [PubMed]).

That is, one disruptive technology that fits any bacteria, any research topic and any laboratory.


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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