title: The Human Skin Microbiome Associates with the Outcome of and Is Influenced by Bacterial Infection.
abstract: The influence of the skin microbiota on host susceptibility to infectious agents is largely unexplored. The skin harbors diverse bacterial species that may promote or antagonize the growth of an invading pathogen. We developed a human infection model for Haemophilus ducreyi in which human volunteers are inoculated on the upper arm. After inoculation, papules form and either spontaneously resolve or progress to pustules. To examine the role of the skin microbiota in the outcome of H. ducreyi infection, we analyzed the microbiomes of four dose-matched pairs of "resolvers" and "pustule formers" whose inoculation sites were swabbed at multiple time points. Bacteria present on the skin were identified by amplification and pyrosequencing of 16S rRNA genes. Nonmetric multidimensional scaling (NMDS) using Bray-Curtis dissimilarity between the preinfection microbiomes of infected sites showed that sites from the same volunteer clustered together and that pustule formers segregated from resolvers (P = 0.001, permutational multivariate analysis of variance [PERMANOVA]), suggesting that the preinfection microbiomes were associated with outcome. NMDS using Bray-Curtis dissimilarity of the endpoint samples showed that the pustule sites clustered together and were significantly different than the resolved sites (P = 0.001, PERMANOVA), suggesting that the microbiomes at the endpoint differed between the two groups. In addition to H. ducreyi, pustule-forming sites had a greater abundance of Proteobacteria, Bacteroidetes, Micrococcus, Corynebacterium, Paracoccus, and Staphylococcus species, whereas resolved sites had higher levels of Actinobacteria and Propionibacterium species. These results suggest that at baseline, resolvers and pustule formers have distinct skin bacterial communities which change in response to infection and the resultant immune response.
  
  
  OBJECTIVE
  Human skin is home to a diverse community of microorganisms, collectively known as the skin microbiome. Some resident bacteria are thought to protect the skin from infection by outcompeting pathogens for resources or by priming the immune system's response to invaders. However, the influence of the skin microbiome on the susceptibility to or protection from infection has not been prospectively evaluated in humans. We characterized the skin microbiome before, during, and after experimental inoculation of the arm with Haemophilus ducreyi in matched volunteers who subsequently resolved the infection or formed abscesses. Our results suggest that the preinfection microbiomes of pustule formers and resolvers have distinct community structures which change in response to the progression of H. ducreyi infection to abscess formation.
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Julia J
authors.initials: JJ
authors.lastname: van Rensburg
authors.affiliation: Department of Public Health Sciences, Center for Biomedical Informatics, Loyola University Chicago, Maywood, Illinois, USA.
authors.forename: Huaiying
authors.initials: H
authors.lastname: Lin
authors.affiliation: Department of Public Health Sciences, Center for Biomedical Informatics, Loyola University Chicago, Maywood, Illinois, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Toh
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Kate R
authors.initials: KR
authors.lastname: Fortney
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Sheila
authors.initials: S
authors.lastname: Ellinger
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Beth
authors.initials: B
authors.lastname: Zwickl
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Diane M
authors.initials: DM
authors.lastname: Janowicz
authors.affiliation: Department of Biostatistics, Indiana University School of Medicine, Indianapolis, Indiana, USA Department of Biostatistics, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, Indiana, USA.
authors.forename: Barry P
authors.initials: BP
authors.lastname: Katz
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Nelson
authors.affiliation: Department of Public Health Sciences, Center for Biomedical Informatics, Loyola University Chicago, Maywood, Illinois, USA.
authors.forename: Qunfeng
authors.initials: Q
authors.lastname: Dong
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA Center for Immunobiology, Indiana University School of Medicine, Indianapolis, Indiana, USA sspinola@iu.edu.
authors.forename: Stanley M
authors.initials: SM
authors.lastname: Spinola
mesh_terms: D016000:Cluster Analysis; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D004275:DNA, Ribosomal / Q000737:chemistry / Q000235:genetics; D006191:Haemophilus ducreyi / Q000254:growth & development*; D006801:Humans; D064307:Microbiota; D008969:Molecular Sequence Data; D010802:Phylogeny; D011446:Prospective Studies; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D017422:Sequence Analysis, DNA; D012867:Skin / Q000382:microbiology*; D017192:Skin Diseases, Bacterial / Q000382:microbiology* / Q000473:pathology*
chemical_list: D004269:DNA, Bacterial; D004275:DNA, Ribosomal; D012336:RNA, Ribosomal, 16S