Research ArticleMicrobiome

Staphylococcus aureus and Staphylococcus epidermidis strain diversity underlying pediatric atopic dermatitis

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Science Translational Medicine  05 Jul 2017:
Vol. 9, Issue 397, eaal4651
DOI: 10.1126/scitranslmed.aal4651
  • Fig. 1. Bacterial communities shift during AD disease progression.

    (A) Objective SCORAD for patients at baseline (n = 5), flare, and post-flare (n = 11). Higher SCORAD corresponds to more severe disease. ***P < 0.001, with nonparametric Wilcoxon rank-sum test. (B) Mean Shannon diversity ± SEM in controls and AD disease states. Colors correspond to disease state. Vf, volar forearm; Ic, inguinal crease; Fh, forehead; Oc, occiput; Ra, retroauricular crease. (C) Shannon diversity versus objective SCORAD for AcPc of AD patients. Pearson partial correlation (adjusting for disease state). (D) Mean relative abundance of bacterial genera in AcPc for controls and AD disease states. (E) Mean relative abundance of predominant genera in AcPc for disease states. Statistical significance based on paired Wilcoxon test and Bonferroni correction. F, flare; PF, post-flare. (F) Proportion of Staphylococcus versus objective SCORAD for AcPc of AD patients. Pearson partial correlation (adjusting for disease state).

  • Fig. 2. Staphylococcal species increase during AD disease flare.

    (A) Mean relative abundance of staphylococcal species within the total bacterial population in AcPc of AD patients and controls. (B) Mean relative abundance of most abundant Staphylococcus species in AcPc for disease states. Statistical significance based on paired Wilcoxon test. (C) Correlation of S. aureus (left) and S. epidermidis (right) mean relative abundance and objective SCORAD for AcPc of patients. Pearson partial correlation (adjusting for disease state). (D) Comparison of S. aureus to S. epidermidis relative abundance by patient for all sites. The patient’s objective SCORAD is indicated in the parenthesis. Shape corresponds to physiological characteristic of the body site, color to the predominant species, and size to the magnitude of disease severity (objective SCORAD). Patients at the top row have a higher predominance of S. epidermidis, whereas patients at the bottom row are S. aureus–predominant.

  • Fig. 3. S. aureus–predominant individuals are often colonized with a single S. aureus strain.

    (A) Dendogram of 61 representative S. aureus strains based on SNVs in the core genome. Strains labeled in red were isolated from patients in (B). Colored blocks correspond to genomes of the same clade. Phylogenetically distant clade F1 is shown as an outgroup because it was recently reclassified as Staphylococcus argenteus (34). (B) For S. aureus–predominant individuals (N = 5), S. aureus clade relative abundances in bilateral Acs and Pcs for AD disease states, flare and post-flare. Colors correspond to those in (A). (C) For combined samples of all sites/time points of individuals in (B), bar charts show the number of SNVs per individual that are mono-, bi-, and triallelic. (D) Venn diagram showing the number of genes shared between isolates from patients in (B), indicated in red in (A).

  • Fig. 4. S. epidermidis–predominant individuals are colonized by a heterogenous community of S. epidermidis strains.

    (A) Dendogram of S. epidermidis strains based on SNVs in the core genome. Strains isolated from patients in our study are labeled in red. Similar colors represent closely related strains that were grouped into 14 clades. Starred (*) isolates are nosocomial in origin. (B) For S. epidermidis–predominant individuals (n = 6), S. epidermidis strain relative abundances in AcPc for AD disease states, flare and post-flare. Colors correspond to those in (A). (C) Heatmap shows mean relative abundance of each clade across all sites in S. aureus– and S. epidermidis–predominant AD patients, healthy adults, and healthy children. (D) In principal component (PC) analysis, clades A20, A29, and A30 drive separation between S. epidermidis–predominant AD patients and healthy adults.

  • Fig. 5. Topical application of AD isolates induces AD-like cutaneous immune responses in murine models.

    (A) Representative histological images of the ear pinnae of mice associated with tryptic soy broth (TSB); S. aureus AD04.E17, HC.B1, and USA300; or S. epidermidis A10.A30. Dotted line indicates separation between the epidermidis and dermis. Scale bars, 50 μm. (B) Epidermal thickness of ears after topical association of patient AD isolates. Color indicates origin and species of the isolate. (C) Absolute numbers of skin eosinophils, gated on Lineage, Ly6G, MHCII, CD64, and SiglecF+. (D) Absolute numbers of skin CD45+ TCRβ+ CD4+ cells. (E) Absolute numbers of skin IL-13+ TCRβ+ CD4+ cells. (F) Absolute numbers of skin IL-17A+ TCRβ+ CD4+cells. (G) Frequencies of IL-13+ and IL-17A+ CD4+ cells from mice in (B). Results are cumulative data from two or three independent experiments, with three mice per group. *P < 0.05, **P < 0.01, and ***P < 0.001, as calculated by analysis of variance (ANOVA) with multiple comparison correction.

Supplementary Materials

  • www.sciencetranslationalmedicine.org/cgi/content/full/9/397/eaal4651/DC1

    Materials and Methods

    Fig. S1. Seven sites sampled bilaterally on pediatric AD patients and control children.

    Fig. S2. Full multikingdom taxonomic classifications for AD patients and controls.

    Fig. S3. Full Malassezia species classifications for AD patients and controls.

    Fig. S4. Full eukaryotic virus classifications for AD patients and controls.

    Fig. S5. Full bacterial taxonomic classifications for AD patients and controls.

    Fig. S6. Relative abundance of staphylococcal species in relation to total bacterial population for all sites in AD patients and controls.

    Fig. S7. Correlation of various staphylococcal species mean relative abundance and objective SCORAD for all sites of patients.

    Fig. S8. Relative abundance of staphylococcal species for all sites in AD patients and controls.

    Fig. S9. S. aureus clades for AD patients and controls.

    Fig. S10. S. epidermidis clades for AD patients and controls.

    Fig. S11. Histologic and cutaneous innate immune cell responses with AD isolate association in a murine model.

    Fig. S12. CD45+ cutaneous immune responses with AD isolate association in a murine model.

    Table S1. Subject Tanner stage and disease severity for samples used in this study.

    Table S2. Clinical metadata for the subjects in this study.

    Table S3. Metadata table for all samples in this study.

    Table S4. Multikingdom relative abundances (coverage, >1% of the reference genome).

    Table S5. Malassezia relative abundance.

    Table S6. Bacteria relative abundances (coverage, >1% of the reference genome).

    Table S7. Staphylococcus species relative abundances.

    Table S8. S. aureus clade abundances.

    Table S9. S. aureus pangenome analysis for isolates cultured and sequenced in this study.

    Table S10. S. epidermidis strain relative abundances.

    References (6975)

  • Supplementary Material for:

    Staphylococcus aureus and Staphylococcus epidermidis strain diversity underlying pediatric atopic dermatitis

    Allyson L. Byrd, Clay Deming, Sara K. B. Cassidy, Oliver J. Harrison, Weng-Ian Ng, Sean Conlan, Yasmine Belkaid, Julia A. Segre,* Heidi H. Kong*

    *Corresponding author. Email: jsegre{at}mail.nih.gov (J.A.S.); konghe{at}mail.nih.gov (H.H.K.)

    Published 5 July 2017, Sci. Transl. Med. 9, eaal4651 (2017)
    DOI: 10.1126/scitranslmed.aal4651

    This PDF file includes:

    • Materials and Methods
    • Fig. S1. Seven sites sampled bilaterally on pediatric AD patients and control children.
    • Fig. S2. Full multikingdom taxonomic classifications for AD patients and controls.
    • Fig. S3. Full Malassezia species classifications for AD patients and controls.
    • Fig. S4. Full eukaryotic virus classifications for AD patients and controls.
    • Fig. S5. Full bacterial taxonomic classifications for AD patients and controls.
    • Fig. S6. Relative abundance of staphylococcal species in relation to total bacterial population for all sites in AD patients and controls.
    • Fig. S7. Correlation of various staphylococcal species mean relative abundance and objective SCORAD for all sites of patients.
    • Fig. S8. Relative abundance of staphylococcal species for all sites in AD patients and controls.
    • Fig. S9. S. aureus clades for AD patients and controls.
    • Fig. S10. S. epidermidis clades for AD patients and controls.
    • Fig. S11. Histologic and cutaneous innate immune cell responses with AD isolate association in a murine model.
    • Fig. S12. CD45+ cutaneous immune responses with AD isolate association in a murine model.
    • Table S1. Subject Tanner stage and disease severity for samples used in this study.
    • Table S2. Clinical metadata for the subjects in this study.
    • References (6975)

    [Download PDF]

    Other Supplementary Material for this manuscript includes the following:

    • Table S3 (Microsoft Excel format). Metadata table for all samples in this study.
    • Table S4 (Microsoft Excel format). Multikingdom relative abundances (coverage, >1% of the reference genome).
    • Table S5 (Microsoft Excel format). Malassezia relative abundance.
    • Table S6 (Microsoft Excel format). Bacteria relative abundances (coverage, >1% of the reference genome).
    • Table S7 (Microsoft Excel format). Staphylococcus species relative abundances.
    • Table S8 (Microsoft Excel format). S. aureus clade abundances.
    • Table S9 (Microsoft Excel format). S. aureus pangenome analysis for isolates cultured and sequenced in this study.
    • Table S10 (Microsoft Excel format). S. epidermidis strain relative abundances.

    [Download Tables S3 to S10]

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