NIH Human Microbiome Project

2009 ◽  
Vol 4 (9) ◽  
pp. 393-393
Keyword(s):  
Human Microbiome ◽  
Human Microbiome Project

scholarly journals Sequence Comparison of Vaginolysin from Different Gardnerella Species

Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 86
Author(s):  
Erin M. Garcia ◽  
Myrna G. Serrano ◽  
Laahirie Edupuganti ◽  
David J. Edwards ◽  
Gregory A. Buck ◽  
...  
Keyword(s):  
Amino Acid ◽  
Human Microbiome ◽  
Human Microbiome Project ◽  
Distinct Species ◽  
Vaginal Swab ◽  
Metagenomic Data ◽  
Gardnerella Vaginalis ◽  
Vaginal Epithelial Cells ◽  
Species Specific

Gardnerella vaginalis has recently been split into 13 distinct species. In this study, we tested the hypotheses that species-specific variations in the vaginolysin (VLY) amino acid sequence could influence the interaction between the toxin and vaginal epithelial cells and that VLY variation may be one factor that distinguishes less virulent or commensal strains from more virulent strains. This was assessed by bioinformatic analyses of publicly available Gardnerella spp. sequences and quantification of cytotoxicity and cytokine production from purified, recombinantly produced versions of VLY. After identifying conserved differences that could distinguish distinct VLY types, we analyzed metagenomic data from a cohort of female subjects from the Vaginal Human Microbiome Project to investigate whether these different VLY types exhibited any significant associations with symptoms or Gardnerella spp.-relative abundance in vaginal swab samples. While Type 1 VLY was most prevalent among the subjects and may be associated with increased reports of symptoms, subjects with Type 2 VLY dominant profiles exhibited increased relative Gardnerella spp. abundance. Our findings suggest that amino acid differences alter the interaction of VLY with vaginal keratinocytes, which may potentiate differences in bacterial vaginosis (BV) immunopathology in vivo.

scholarly journals Competition among Nasal Bacteria Suggests a Role for Siderophore-Mediated Interactions in Shaping the Human Nasal Microbiota

2018 ◽  
Vol 85 (10) ◽  
Author(s):  
Reed M. Stubbendieck ◽  
Daniel S. May ◽  
Marc G. Chevrette ◽  
Mia I. Temkin ◽  
Evelyn Wendt-Pienkowski ◽  
...  
Keyword(s):  
Nasal Cavity ◽  
Iron Acquisition ◽  
Interference Competition ◽  
Human Microbiome ◽  
Human Microbiome Project ◽  
Siderophore Production ◽  
Coagulase Negative Staphylococci ◽  
Exploitation Competition ◽  
Content Type

ABSTRACTResources available in the human nasal cavity are limited. Therefore, to successfully colonize the nasal cavity, bacteria must compete for scarce nutrients. Competition may occur directly through interference (e.g., antibiotics) or indirectly by nutrient sequestration. To investigate the nature of nasal bacterial competition, we performed coculture inhibition assays between nasalActinobacteriaandStaphylococcusspp. We found that isolates of coagulase-negative staphylococci (CoNS) were sensitive to growth inhibition byActinobacteriabut thatStaphylococcus aureusisolates were resistant to inhibition. AmongActinobacteria, we observed thatCorynebacteriumspp. were variable in their ability to inhibit CoNS. We sequenced the genomes of 10Corynebacteriumspecies isolates, including 3Corynebacterium propinquumisolates that strongly inhibited CoNS and 7 otherCorynebacteriumspecies isolates that only weakly inhibited CoNS. Using a comparative genomics approach, we found that theC. propinquumgenomes were enriched in genes for iron acquisition and harbored a biosynthetic gene cluster (BGC) for siderophore production, absent in the noninhibitoryCorynebacteriumspecies genomes. Using a chrome azurol S assay, we confirmed thatC. propinquumproduced siderophores. We demonstrated that iron supplementation rescued CoNS from inhibition byC. propinquum, suggesting that inhibition was due to iron restriction through siderophore production. Through comparative metabolomics and molecular networking, we identified the siderophore produced byC. propinquumas dehydroxynocardamine. Finally, we confirmed that the dehydroxynocardamine BGC is expressedin vivoby analyzing human nasal metatranscriptomes from the NIH Human Microbiome Project. Together, our results suggest that bacteria produce siderophores to compete for limited available iron in the nasal cavity and improve their fitness.IMPORTANCEWithin the nasal cavity, interference competition through antimicrobial production is prevalent. For instance, nasalStaphylococcusspecies strains can inhibit the growth of other bacteria through the production of nonribosomal peptides and ribosomally synthesized and posttranslationally modified peptides. In contrast, bacteria engaging in exploitation competition modify the external environment to prevent competitors from growing, usually by hindering access to or depleting essential nutrients. As the nasal cavity is a nutrient-limited environment, we hypothesized that exploitation competition occurs in this system. We determined thatCorynebacterium propinquumproduces an iron-chelating siderophore, and this iron-sequestering molecule correlates with the ability to inhibit the growth of coagulase-negative staphylococci. Furthermore, we found that the genes required for siderophore production are expressedin vivo. Thus, although siderophore production by bacteria is often considered a virulence trait, our work indicates that bacteria may produce siderophores to compete for limited iron in the human nasal cavity.

scholarly journals MetaCompass: Reference-guided Assembly of Metagenomes

2017 ◽  
Author(s):  
Victoria Cepeda ◽  
Bo Liu ◽  
Mathieu Almeida ◽  
Christopher M. Hill ◽  
Sergey Koren ◽  
...  
Keyword(s):  
De Novo ◽  
Human Microbiome ◽  
Human Microbiome Project ◽  
Bacterial Genomes ◽  
Guided Assembly ◽  
Metagenomic Assembly

ABSTRACTMetagenomic studies have primarily relied on de novo approaches for reconstructing genes and genomes from microbial mixtures. While database driven approaches have been employed in certain analyses, they have not been used in the assembly of metagenomes. Here we describe the first effective approach for reference-guided metagenomic assembly of low-abundance bacterial genomes that can complement and improve upon de novo metagenomic assembly methods. When combined with de novo assembly approaches, we show that MetaCompass can generate more complete assemblies than can be obtained by de novo assembly alone, and improve on assemblies from the Human Microbiome Project (over 2,000 samples).

scholarly journals Misclassification of a whole genome sequence reference defined by the Human Microbiome Project: a detrimental carryover effect to microbiome studies

2019 ◽  
Author(s):  
DJ Darwin R. Bandoy ◽  
B Carol Huang ◽  
Bart C. Weimer
Keyword(s):  
Human Microbiome ◽  
Human Microbiome Project ◽  
Outbreak Detection ◽  
Whole Genome Sequence ◽  
Reference Database ◽  
Whole Genome ◽  
Reference Species ◽  
Genome Sequences ◽  
Genome Homology ◽  
Microbiome Data

AbstractTaxonomic classification is an essential step in the analysis of microbiome data that depends on a reference database of whole genome sequences. Taxonomic classifiers are built on established reference species, such as the Human Microbiome Project database, that is growing rapidly. While constructing a population wide pangenome of the bacterium Hungatella, we discovered that the Human Microbiome Project reference species Hungatella hathewayi (WAL 18680) was significantly different to other members of this genus. Specifically, the reference lacked the core genome as compared to the other members. Further analysis, using average nucleotide identity (ANI) and 16s rRNA comparisons, indicated that WAL18680 was misclassified as Hungatella. The error in classification is being amplified in the taxonomic classifiers and will have a compounding effect as microbiome analyses are done, resulting in inaccurate assignment of community members and will lead to fallacious conclusions and possibly treatment. As automated genome homology assessment expands for microbiome analysis, outbreak detection, and public health reliance on whole genomes increases this issue will likely occur at an increasing rate. These observations highlight the need for developing reference free methods for epidemiological investigation using whole genome sequences and the criticality of accurate reference databases.

scholarly journals Mouse Gut Microbiome-Encoded β-Glucuronidases Identified Using Metagenome Analysis Guided by Protein Structure

mSystems ◽  
2019 ◽  
Vol 4 (4) ◽  
Author(s):  
Benjamin C. Creekmore ◽  
Josh H. Gray ◽  
William G. Walton ◽  
Kristen A. Biernat ◽  
Michael S. Little ◽  
...  
Keyword(s):  
Protein Structure ◽  
Active Site ◽  
Human Microbiome ◽  
Drug Efficacy ◽  
Human Microbiome Project ◽  
Structural Features ◽  
Model Organisms ◽  
Mouse Strains ◽  
Sequencing Data ◽  
Metagenome Analysis

ABSTRACT Gut microbial β-glucuronidase (GUS) enzymes play important roles in drug efficacy and toxicity, intestinal carcinogenesis, and mammalian-microbial symbiosis. Recently, the first catalog of human gut GUS proteins was provided for the Human Microbiome Project stool sample database and revealed 279 unique GUS enzymes organized into six categories based on active-site structural features. Because mice represent a model biomedical research organism, here we provide an analogous catalog of mouse intestinal microbial GUS proteins—a mouse gut GUSome. Using metagenome analysis guided by protein structure, we examined 2.5 million unique proteins from a comprehensive mouse gut metagenome created from several mouse strains, providers, housing conditions, and diets. We identified 444 unique GUS proteins and organized them into six categories based on active-site features, similarly to the human GUSome analysis. GUS enzymes were encoded by the major gut microbial phyla, including Firmicutes (60%) and Bacteroidetes (21%), and there were nearly 20% for which taxonomy could not be assigned. No differences in gut microbial gus gene composition were observed for mice based on sex. However, mice exhibited gus differences based on active-site features associated with provider, location, strain, and diet. Furthermore, diet yielded the largest differences in gus composition. Biochemical analysis of two low-fat-associated GUS enzymes revealed that they are variable with respect to their efficacy of processing both sulfated and nonsulfated heparan nonasaccharides containing terminal glucuronides. IMPORTANCE Mice are commonly employed as model organisms of mammalian disease; as such, our understanding of the compositions of their gut microbiomes is critical to appreciating how the mouse and human gastrointestinal tracts mirror one another. GUS enzymes, with importance in normal physiology and disease, are an attractive set of proteins to use for such analyses. Here we show that while the specific GUS enzymes differ at the sequence level, a core GUSome functionality appears conserved between mouse and human gastrointestinal bacteria. Mouse strain, provider, housing location, and diet exhibit distinct GUSomes and gus gene compositions, but sex seems not to affect the GUSome. These data provide a basis for understanding the gut microbial GUS enzymes present in commonly used laboratory mice. Further, they demonstrate the utility of metagenome analysis guided by protein structure to provide specific sets of functionally related proteins from whole-genome metagenome sequencing data.

scholarly journals Metapangenomics of the oral microbiome provides insights into habitat adaptation and cultivar diversity

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Daniel R. Utter ◽  
Gary G. Borisy ◽  
A. Murat Eren ◽  
Colleen M. Cavanaugh ◽  
Jessica L. Mark Welch
Keyword(s):  
Buccal Mucosa ◽  
Habitat Preferences ◽  
Human Microbiome ◽  
Human Microbiome Project ◽  
Oral Microbiome ◽  
Functional Enrichment ◽  
Habitat Adaptation ◽  
Haemophilus Parainfluenzae ◽  
Population Structures ◽  
Genome Content

Abstract Background The increasing availability of microbial genomes and environmental shotgun metagenomes provides unprecedented access to the genomic differences within related bacteria. The human oral microbiome with its diverse habitats and abundant, relatively well-characterized microbial inhabitants presents an opportunity to investigate bacterial population structures at an ecosystem scale. Results Here, we employ a metapangenomic approach that combines public genomes with Human Microbiome Project (HMP) metagenomes to study the diversity of microbial residents of three oral habitats: tongue dorsum, buccal mucosa, and supragingival plaque. For two exemplar taxa, Haemophilus parainfluenzae and the genus Rothia, metapangenomes reveal distinct genomic groups based on shared genome content. H. parainfluenzae genomes separate into three distinct subgroups with differential abundance between oral habitats. Functional enrichment analyses identify an operon encoding oxaloacetate decarboxylase as diagnostic for the tongue-abundant subgroup. For the genus Rothia, grouping by shared genome content recapitulates species-level taxonomy and habitat preferences. However, while most R. mucilaginosa are restricted to the tongue as expected, two genomes represent a cryptic population of R. mucilaginosa in many buccal mucosa samples. For both H. parainfluenzae and the genus Rothia, we identify not only limitations in the ability of cultivated organisms to represent populations in their native environment, but also specifically which cultivar gene sequences are absent or ubiquitous. Conclusions Our findings provide insights into population structure and biogeography in the mouth and form specific hypotheses about habitat adaptation. These results illustrate the power of combining metagenomes and pangenomes to investigate the ecology and evolution of bacteria across analytical scales.

scholarly journals Computational Modeling of the Human Microbiome

2020 ◽  
Vol 8 (2) ◽  
pp. 197
Author(s):  
Shomeek Chowdhury ◽  
Stephen S. Fong
Keyword(s):  
Computational Modeling ◽  
Human Health ◽  
Large Scale ◽  
Human Microbiome ◽  
Human Microbiome Project ◽  
Microbial Composition ◽  
Site Specific ◽  
Microbiome Research ◽  
High Level ◽  
The Impact

The impact of microorganisms on human health has long been acknowledged and studied, but recent advances in research methodologies have enabled a new systems-level perspective on the collections of microorganisms associated with humans, the human microbiome. Large-scale collaborative efforts such as the NIH Human Microbiome Project have sought to kick-start research on the human microbiome by providing foundational information on microbial composition based upon specific sites across the human body. Here, we focus on the four main anatomical sites of the human microbiome: gut, oral, skin, and vaginal, and provide information on site-specific background, experimental data, and computational modeling. Each of the site-specific microbiomes has unique organisms and phenomena associated with them; there are also high-level commonalities. By providing an overview of different human microbiome sites, we hope to provide a perspective where detailed, site-specific research is needed to understand causal phenomena that impact human health, but there is equally a need for more generalized methodology improvements that would benefit all human microbiome research.

scholarly journals Evaluative Profiling of Arsenic Sensing and Regulatory Systems in the Human Microbiome Project Genomes

2014 ◽  
Vol 7 ◽  
pp. MBI.S18076 ◽  
Author(s):  
Raphael D. Isokpehi ◽  
Udensi K. Udensi ◽  
Shaneka S. Simmons ◽  
Antoinesha L. Hollman ◽  
Antia E. Cain ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Visual Analytics ◽  
Energy Production ◽  
Human Microbiome ◽  
Human Microbiome Project ◽  
Environmental Chemicals ◽  
Arsenic Content ◽  
Protein Families ◽  
Arsenic Resistance ◽  
Cellular Energy

The influence of environmental chemicals including arsenic, a type 1 carcinogen, on the composition and function of the human-associated microbiota is of significance in human health and disease. We have developed a suite of bioinformatics and visual analytics methods to evaluate the availability (presence or absence) and abundance of functional annotations in a microbial genome for seven Pfam protein families: As(III)-responsive transcriptional repressor (ArsR), anion-transporting ATPase (ArsA), arsenical pump membrane protein (ArsB), arsenate reductase (ArsC), arsenical resistance operon transacting repressor (ArsD), water/glycerol transport protein (aquaporins), and universal stress protein (USP). These genes encode function for sensing and/or regulating arsenic content in the bacterial cell. The evaluative profiling strategy was applied to 3,274 genomes from which 62 genomes from 18 genera were identified to contain genes for the seven protein families. Our list included 12 genomes in the Human Microbiome Project (HMP) from the following genera: Citrobacter, Escherichia, Lactobacillus, Providencia, Rhodococcus, and Staphylococcus. Gene neighborhood analysis of the arsenic resistance operon in the genome of Bacteroides thetaiotaomicron VPI-5482, a human gut symbiont, revealed the adjacent arrangement of genes for arsenite binding/transfer (ArsD) and cytochrome c biosynthesis (DsbD_2). Visual analytics facilitated evaluation of protein annotations in 367 genomes in the phylum Bacteroidetes identified multiple genomes in which genes for ArsD and DsbD_2 were adjacently arranged. Cytochrome c, produced by a posttranslational process, consists of heme-containing proteins important for cellular energy production and signaling. Further research is desired to elucidate arsenic resistance and arsenic-mediated cellular energy production in the Bacteroidetes.

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