A Bit of a Mouthful James Hadfield & Sophia David

NEWS & ANALYSIS

GENOME WATCH A bit of a mouthful James Hadfield & Sophia David

This month’s Genome Watch explores One recent study applied various methods sequence typing (MLST) alleles in each sam- recent advances in the identification of to explore the diversity of the Neisseria genus ple also supported the associations between species-level and strain-level diversity in within the human oral cavity4. Neisseria spe- specific species and tissues. microbiome studies, and highlights how cies are closely related and undergo frequent To probe even deeper than the species-level, these have provided insights into the recombination, which makes the identifi- the authors used a panel of strain-specific tropism and persistence of Neisseria spp. cation of individual species and strains par- marker genes, revealing fascinating results. in the human oral cavity. ticularly challenging. Using a large reference Although the same sites across different collection of 241 draft and complete genomes patients were colonized by the same species, Metagenomics provides a powerful approach that belong to the Neisseriaceae family, individual patients harboured unique vari to survey complex microbial communities, the authors used a custom mapping-based ants, or strains, of the species. Moreover, such as those that are associated with humans, approach to analyse SNP patterns. They longitudinal sampling revealed that the pres- without the need for culture. Previous studies successfully identified different species from ence of these strains was stable within indi- have identified microbial taxa linked to many oral microbiome samples, revealing intricate vidual patients. These important findings are disease states, including autoimmune disor- associations between tissues and species. only possible owing to the high accuracy of ders and obesity. However, until recently, most Different oral sites within the same these new approaches. studies that probe the variation of microorgan- patients were enriched for different species, Microbiome studies are advancing rapidly, isms within metagenome samples have been but, remarkably, the same sites across differ- and these latest tools bring us one step closer limited to detecting high-level taxa. However, ent patients showed marked similarities. For to fully characterizing and understanding different species, and even strains of the same example, Neisseria flavescens and Neisseria the implications of the astounding diversity species, can have vastly different virulence subflava were generally found on the upper within microbial ecosystems. The increase in and antimicrobial resistance profiles, as well surface of the tongue, whereas Neisseria sicca, resolution beyond species-level detection will as other important phenotypic differences. Neisseria mucosa and Neisseria elongata were be particularly useful in identifying further Recent advances in metagenomic analysis ena- found to populate the gingival (gum) plaque. associations with disease states, and under- ble both species-level and strain-level detection Neisseria meningitidis, an important cause standing the spatial composition and function and provide exciting new insights that were of sepsis and bacterial meningitis in young of microbial communities. These advances previously masked by the higher-level findings. adults, was found only in a small number of will also enable us to better understand dis- New methods for uncovering species-level throat samples. The authors confirmed their ease risk, infer transmission events, character- and strain-level variation of bacteria within results by identifying short, 12-nucleotide- ize antibiotic resistance profiles and identify a community are taking advantage of the long features within the Neisseria genomes strains that are present in co-infections. increasing number of reference genomes that called DNA uptake sequences (DUSs), which James Hadfield and Sophia David are at the Sanger are available. A common approach used by are unique to distinct clades of Neisseria Institute, Wellcome Trust Genome Campus, Hinxton, both Ahn et al.1 and Sankar et al.2 has been species. Analysis of the dominant multilocus Cambridge CB10 1SA, UK. to map the sequence reads simultaneously to e‑mail: [email protected] multiple reference genomes, or core genomes, doi:10.1038/nrmicro.2016.124 of a target species. Statistical models are then Published online 11 Aug 2016 1. Ahn, T. H., Chai, J. & Pan, C. Sigma:Strain-level used to infer the relative abundance of each inference of genomes from metagenomic analysis for species and/or strain based on patterns of biosurveillance. Bioinformatics 31, 170–177 (2015). 2. Sankar, A. et al. Bayesian identification of bacterial polymorphisms. As the number of available strains from sequencing data. Microb. Genom. reference genomes of a given species contin- http://dx.doi.org/10.1099/mgen.0.000075 (2016). 3. Luo, C. W. et al. ConStrains identifies microbial strains ues to increase, so will the resolution of these in metagenomic datasets. Nat. Biotechnol. 33, methods. For species that are not yet so well 1045–1052 (2015). 4. Donati, C. et al. Uncovering oral Neisseria tropism represented, other SNP-based methods such and persistence using metagenomic sequencing. as those developed by Luo et al.3 make use Nat. Microbiol. 1, 16070 (2016). of just one reference genome for detecting Competing interests statement strain-level variation within a target species. The authors declare no competing interests. NPG