title: Uncovering oral Neisseria tropism and persistence using metagenomic sequencing.
abstract: Microbial epidemiology and population genomics have previously been carried out near-exclusively for organisms grown in vitro. Metagenomics helps to overcome this limitation, but it is still challenging to achieve strain-level characterization of microorganisms from culture-independent data with sufficient resolution for epidemiological modelling. Here, we have developed multiple complementary approaches that can be combined to profile and track individual microbial strains. To specifically profile highly recombinant neisseriae from oral metagenomes, we integrated four metagenomic analysis techniques: single nucleotide polymorphisms in the clade's core genome, DNA uptake sequence signatures, metagenomic multilocus sequence typing and strain-specific marker genes. We applied these tools to 520 oral metagenomes from the Human Microbiome Project, finding evidence of site tropism and temporal intra-subject strain retention. Although the opportunistic pathogen Neisseria meningitidis is enriched for colonization in the throat, N. flavescens and N. subflava populate the tongue dorsum, and N. sicca, N. mucosa and N. elongata the gingival plaque. The buccal mucosa appeared as an intermediate ecological niche between the plaque and the tongue. The resulting approaches to metagenomic strain profiling are generalizable and can be extended to other organisms and microbiomes across environments.
authors: Computational Biology Unit, Research and Innovation Centre, Fondazione Edmund Mach, Via Edmund Mach 1, 38010 San Michele All'adige, Italy.
authors: Claudio
authors: C
authors: Donati
authors: Centre for Integrative Biology, University of Trento, Via Sommarive 9, 38123 Trento, Italy.
authors: Moreno
authors: 0000-0001-6661-4046
authors: M
authors: Zolfo
authors: Computational Biology Unit, Research and Innovation Centre, Fondazione Edmund Mach, Via Edmund Mach 1, 38010 San Michele All'adige, Italy.
authors: Davide
authors: 0000-0002-9493-3850
authors: D
authors: Albanese
authors: Centre for Integrative Biology, University of Trento, Via Sommarive 9, 38123 Trento, Italy.
authors: Duy
authors: 0000-0002-4169-7727
authors: D
authors: Tin Truong
authors: Centre for Integrative Biology, University of Trento, Via Sommarive 9, 38123 Trento, Italy.
authors: Francesco
authors: F
authors: Asnicar
authors: Department of Public Health and Infectious Diseases, Institute Pasteur Cenci Bolognetti Foundation, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Roma, Italy.
authors: Valerio
authors: V
authors: Iebba
authors: Department of Biology, University of Florence, Via Madonna del Piano 6, 50019 Sesto Fiorentino, Firenze, Italy.|Institute of Biometeorology, National Research Council (IBIMET-CNR), Via Caproni 8, 50145 Firenze, Italy.
authors: Duccio
authors: D
authors: Cavalieri
authors: Centre for Integrative Biology, University of Trento, Via Sommarive 9, 38123 Trento, Italy.
authors: Olivier
authors: O
authors: Jousson
authors: Institute of Biometeorology, National Research Council (IBIMET-CNR), Via Caproni 8, 50145 Firenze, Italy.
authors: Carlotta
authors: 0000-0002-2222-6524
authors: C
authors: De Filippo
authors: Biostatistics Department, Harvard School of Public Health, Boston, Massachusetts 02115, USA.|Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
authors: Curtis
authors: C
authors: Huttenhower
authors: Centre for Integrative Biology, University of Trento, Via Sommarive 9, 38123 Trento, Italy.
authors: Nicola
authors: 0000-0002-1583-5794
authors: N
authors: Segata
mesh_terms: D039301:Computers, Molecular; D016680:Genome, Bacterial; D005881:Gingiva / Q000382:microbiology; D006801:Humans; D054892:Metagenome; D056186:Metagenomics / Q000379:methods; D064307:Microbiota; D009055:Mouth / Q000382:microbiology*; D058885:Multilocus Sequence Typing; D009343:Neisseria / Q000145:classification / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D010614:Pharynx / Q000382:microbiology; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D014059:Tongue / Q000382:microbiology; D056189:Viral Tropism