First Description of the Composition and the Functional Capabilities of the Skin Microbial Community Accompanying Severe Scabies Infestation in Humans

Epidemiological studies link Sarcoptes scabiei infection and impetigo. Scabies mites can promote Streptococcus pyogenes (Group A Streptococcus) and Staphylococcus aureus infections by breaching the skin barrier and excreting molecules that inhibit host innate immune responses. However, little is known about the composition and the function of the scabies-associated microbiota. Here, high-throughput whole-metagenome sequencing was used to explore the scabies-associated microbiome. Scabies mites including their immediate microenvironments were isolated from two patients with severe scabies in Northern Australia. Two ~45–50 million paired-end reads Illumina libraries were generated of which ~2 (5.1%) and 0.7 million (1.3%) microbial reads were filtered out by mapping to human (hg19) and mite draft genomes. Taxonomic profiling revealed a microbial community dominated by the phylum Firmicutes (A: 79% and B: 59%) and genera that comprise Streptococcus, Staphylococcus, Acinetobacter, and Corynebacterium. Assembly of the metagenome reads resulted in genome bins representing reference genomes of Acinetobacter baumannii, Streptococcus dysgalactiae (Group C/G), Proteus mirablis and Staphylococcus aureus. The contigs contained genes relevant to pathogenicity and antibiotics resistance. Confocal microscopy of a patient skin sample confirmed A. baumannii, Streptococci and S. aureus in scabies mite gut and faeces and the surrounding skin. The study provides fundamental evidence for the association of opportunistic pathogens with scabies infection.

[1]  G. Poulakou,et al.  Skin manifestations of Pseudomonas aeruginosa infections. , 2021, Current opinion in infectious diseases.

[2]  B. Currie,et al.  Crusted scabies; a 2-year prospective study from the Northern Territory of Australia. , 2020, PLoS neglected tropical diseases.

[3]  P. Manghi,et al.  Integrating taxonomic, functional, and strain-level profiling of diverse microbial communities with bioBakery 3 , 2020, bioRxiv.

[4]  P. Speziale,et al.  The Multivalent Role of Fibronectin-Binding Proteins A and B (FnBPA and FnBPB) of Staphylococcus aureus in Host Infections , 2020, Frontiers in Microbiology.

[5]  J. Cichy,et al.  Metagenomic Studies in Inflammatory Skin Diseases , 2020, Current Microbiology.

[6]  D. Raoult,et al.  Molecular identification of head lice collected in Franceville (Gabon) and their associated bacteria , 2020, Parasites & Vectors.

[7]  John-James Wilson,et al.  Genetic Diversity of Pediculus humanus capitis (Phthiraptera: Pediculidae) in Peninsular Malaysia and Molecular Detection of Its Potential Associated Pathogens , 2019, Journal of Medical Entomology.

[8]  K. Fischer,et al.  High-throughput metagenome analysis of the Sarcoptes scabiei internal microbiota and in-situ identification of intestinal Streptomyces sp. , 2019, Scientific Reports.

[9]  R. Shapouri,et al.  Virulence characteristics of multidrug resistant biofilm forming Acinetobacter baumannii isolated from intensive care unit patients , 2019, BMC Infectious Diseases.

[10]  L. C. Fuller,et al.  The public health control of scabies: priorities for research and action , 2019, The Lancet.

[11]  G. Baracco Infections Caused by Group C and G Streptococcus (Streptococcus dysgalactiae subsp. equisimilis and Others): Epidemiological and Clinical Aspects. , 2019, Microbiology spectrum.

[12]  N. Martinelli,et al.  Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) spa type t127, Sequence Type (ST)1, quickly spreads and persists among young pigs. , 2019, Pathogens and disease.

[13]  N. Anstey,et al.  Genomic epidemiology of severe community-onset Acinetobacter baumannii infection , 2019, Microbial genomics.

[14]  Feng Li,et al.  MetaBAT 2: an adaptive binning algorithm for robust and efficient genome reconstruction from metagenome assemblies , 2019, PeerJ.

[15]  I. Ebersberger,et al.  The Acinetobacter trimeric autotransporter adhesin Ata controls key virulence traits of Acinetobacter baumannii , 2019, Virulence.

[16]  D. Zurawski,et al.  Skin and Soft Tissue Models for Acinetobacter baumannii Infection. , 2019, Methods in molecular biology.

[17]  Chen-mei Zhang,et al.  Acinetobacter baumannii meningitis in children: a case series and literature review , 2018, Infection.

[18]  O. Lund,et al.  SCCmecFinder, a Web-Based Tool for Typing of Staphylococcal Cassette Chromosome mec in Staphylococcus aureus Using Whole-Genome Sequence Data , 2018, mSphere.

[19]  M. Fischbach,et al.  Skin microbiota–host interactions , 2018, Nature.

[20]  M. Feldman,et al.  Uncovering the mechanisms of Acinetobacter baumannii virulence , 2017, Nature Reviews Microbiology.

[21]  Neil D. Rawlings,et al.  The MEROPS database of proteolytic enzymes, their substrates and inhibitors in 2017 and a comparison with peptidases in the PANTHER database , 2017, Nucleic Acids Res..

[22]  B. Currie,et al.  Scabies and mortality. , 2017, The Lancet. Infectious diseases.

[23]  L. C. Fuller,et al.  Scratching the itch: is scabies a truly neglected disease? , 2017, The Lancet. Infectious diseases.

[24]  R. Hay,et al.  The global burden of scabies: a cross-sectional analysis from the Global Burden of Disease Study 2015 , 2017, The Lancet. Infectious diseases.

[25]  M. Shneider,et al.  Acinetobacter baumannii K11 and K83 capsular polysaccharides have the same 6-deoxy-l-talose-containing pentasaccharide K units but different linkages between the K units. , 2017, International journal of biological macromolecules.

[26]  Andrea Beaton,et al.  Global, Regional, and National Burden of Rheumatic Heart Disease, 1990–2015 , 2017, The New England journal of medicine.

[27]  É. Marijon,et al.  Rheumatic Heart Disease - An Iceberg in Tropical Waters. , 2017, The New England journal of medicine.

[28]  P. Parola,et al.  Human head lice and pubic lice reveal the presence of several Acinetobacter species in Algiers, Algeria. , 2017, Comparative immunology, microbiology and infectious diseases.

[29]  P. Pevzner,et al.  metaSPAdes: a new versatile metagenomic assembler. , 2017, Genome research.

[30]  Jung Hun Lee,et al.  Biology of Acinetobacter baumannii: Pathogenesis, Antibiotic Resistance Mechanisms, and Prospective Treatment Options , 2017, Front. Cell. Infect. Microbiol..

[31]  Hieng C Lu,et al.  Complement inhibition by Sarcoptes scabiei protects Streptococcus pyogenes - An in vitro study to unravel the molecular mechanisms behind the poorly understood predilection of S. pyogenes to infect mite-induced skin lesions , 2017, PLoS neglected tropical diseases.

[32]  A. Papenfuss,et al.  Genomic resources and draft assemblies of the human and porcine varieties of scabies mites, Sarcoptes scabiei var. hominis and var. suis , 2016, GigaScience.

[33]  M. Bahlo,et al.  Mitochondrial Genome Sequence of the Scabies Mite Provides Insight into the Genetic Diversity of Individual Scabies Infections , 2016, PLoS Neglected Tropical Diseases.

[34]  S. D. Rider,et al.  Draft genome of the scabies mite , 2015, Parasites & Vectors.

[35]  L. Peterson,et al.  Joint Transcriptional Control of Virulence and Resistance to Antibiotic and Environmental Stress in Acinetobacter baumannii , 2015, mBio.

[36]  M. Otto,et al.  Mechanisms of resistance to antimicrobial peptides in staphylococci. , 2015, Biochimica et biophysica acta.

[37]  B. Currie,et al.  High burden of invasive group A streptococcal disease in the Northern Territory of Australia , 2015, Epidemiology and Infection.

[38]  R. Hay,et al.  The Global Epidemiology of Impetigo: A Systematic Review of the Population Prevalence of Impetigo and Pyoderma , 2015, PloS one.

[39]  J. Kaldor,et al.  Prevalence of scabies and impetigo worldwide: a systematic review. , 2015, The Lancet. Infectious diseases.

[40]  Connor T. Skennerton,et al.  CheckM: assessing the quality of microbial genomes recovered from isolates, single cells, and metagenomes , 2015, Genome research.

[41]  Ji‐Hyun Lee,et al.  Vibrio vulnificus Secretes an Insulin-degrading Enzyme That Promotes Bacterial Proliferation in Vivo* , 2015, The Journal of Biological Chemistry.

[42]  Vance G. Fowler,et al.  Staphylococcus aureus Infections: Epidemiology, Pathophysiology, Clinical Manifestations, and Management , 2015, Clinical Microbiology Reviews.

[43]  S. Hultgren,et al.  Urinary tract infections: epidemiology, mechanisms of infection and treatment options , 2015, Nature Reviews Microbiology.

[44]  T. Pengsakul,et al.  Molecular survey of the head louse Pediculus humanus capitis in Thailand and its potential role for transmitting Acinetobacter spp. , 2015, Parasites & Vectors.

[45]  J. Carapetis,et al.  Changes in the clinical and epidemiological features of group A streptococcal bacteraemia in Australia's Northern Territory , 2015, Tropical medicine & international health : TM & IH.

[46]  Chao Xie,et al.  Fast and sensitive protein alignment using DIAMOND , 2014, Nature Methods.

[47]  S. Reynolds,et al.  Parasitic scabies mites and associated bacteria joining forces against host complement defence , 2014, Parasite immunology.

[48]  K. Fischer,et al.  A Scabies Mite Serpin Interferes with Complement-Mediated Neutrophil Functions and Promotes Staphylococcal Growth , 2014, PLoS neglected tropical diseases.

[49]  L. Krause,et al.  Scabies Mites Alter the Skin Microbiome and Promote Growth of Opportunistic Pathogens in a Porcine Model , 2014, PLoS neglected tropical diseases.

[50]  A. Blom,et al.  Scabies Mite Inactive Serine Proteases Are Potent Inhibitors of the Human Complement Lectin Pathway , 2014, PLoS neglected tropical diseases.

[51]  Björn Usadel,et al.  Trimmomatic: a flexible trimmer for Illumina sequence data , 2014, Bioinform..

[52]  Jiajie Zhang,et al.  PEAR: a fast and accurate Illumina Paired-End reAd mergeR , 2013, Bioinform..

[53]  Derrick E. Wood,et al.  Kraken: ultrafast metagenomic sequence classification using exact alignments , 2014, Genome Biology.

[54]  S. Mcgloughlin,et al.  A Novel Clinical Grading Scale to Guide the Management of Crusted Scabies , 2013, PLoS neglected tropical diseases.

[55]  R. Hay,et al.  Scabies: a suitable case for a global control initiative , 2013, Current opinion in infectious diseases.

[56]  Deniz Kuzulugil,et al.  Burden of paediatric pyoderma and scabies in North West Queensland , 2013, Journal of paediatrics and child health.

[57]  Karsten Zengler,et al.  The microbiome extends to subepidermal compartments of normal skin , 2012, Nature Communications.

[58]  A. Ralph,et al.  Group a streptococcal diseases and their global burden. , 2013, Current topics in microbiology and immunology.

[59]  D. Raoult,et al.  Detection of Acinetobacter baumannii in human head and body lice from Ethiopia and identification of new genotypes. , 2012, International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases.

[60]  S. Reynolds,et al.  Complement Inhibitors from Scabies Mites Promote Streptococcal Growth – A Novel Mechanism in Infected Epidermis? , 2012, PLoS neglected tropical diseases.

[61]  J. Mathews,et al.  Post-streptococcal glomerulonephritis is a strong risk factor for chronic kidney disease in later life. , 2012, Kidney international.

[62]  A. Blom,et al.  Novel Scabies Mite Serpins Inhibit the Three Pathways of the Human Complement System , 2011, PloS one.

[63]  R. Durand,et al.  No evidence of Bartonella quintana but detection of Acinetobacter baumannii in head lice from elementary schoolchildren in Paris. , 2011, Comparative immunology, microbiology and infectious diseases.

[64]  J. Carapetis,et al.  Skin disease in the first two years of life in Aboriginal children in East Arnhem Land , 2011, The Australasian journal of dermatology.

[65]  Adam M. Phillippy,et al.  Interactive metagenomic visualization in a Web browser , 2011, BMC Bioinformatics.

[66]  C. Saha,et al.  Identification of staphylococcal protein A in infected atopic dermatitis lesions. , 2010, The Journal of investigative dermatology.

[67]  D. Bessen,et al.  Population Genetics of Streptococcus dysgalactiae Subspecies equisimilis Reveals Widely Dispersed Clones and Extensive Recombination , 2010, PloS one.

[68]  M. Borodovsky,et al.  Ab initio gene identification in metagenomic sequences , 2010, Nucleic acids research.

[69]  M. Adams,et al.  Acinetobacter baumannii-associated skin and soft tissue infections: recognizing a broadening spectrum of disease. , 2010, Surgical infections.

[70]  Richard Durbin,et al.  Fast and accurate long-read alignment with Burrows–Wheeler transform , 2010, Bioinform..

[71]  B. Spellerberg,et al.  E M E R G I N G I N F E C T I O N S I N V I T E D a R T I C L E Human Infections Due to Streptococcus Dysgalactiae Subspecies Equisimilis , 2022 .

[72]  J. Whisstock,et al.  Structural mechanisms of inactivation in scabies mite serine protease paralogues. , 2009, Journal of molecular biology.

[73]  A. Buckle,et al.  System Paralogs Inhibit the Human Complement Scabies Mite Inactivated Serine Protease , 2022 .

[74]  J. Carapetis,et al.  High Burden of Impetigo and Scabies in a Tropical Country , 2009, PLoS neglected tropical diseases.

[75]  C. Deming,et al.  Topographical and Temporal Diversity of the Human Skin Microbiome , 2009, Science.

[76]  M. McDonald,et al.  Community-associated strains of methicillin-resistant Staphylococcus aureus and methicillin-susceptible S. aureus in indigenous Northern Australia: epidemiology and outcomes. , 2009, The Journal of infectious diseases.

[77]  J. Hardie,et al.  Antibiotics, primary symbionts and wing polyphenism in three aphid species. , 2007, Insect biochemistry and molecular biology.

[78]  R. Geffers,et al.  Virulence profiling of Streptococcus dysgalactiae subspecies equisimilis isolated from infected humans reveals 2 distinct genetic lineages that do not segregate with their phenotypes or propensity to cause diseases. , 2007, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[79]  T. Fukatsu,et al.  Selective elimination of aphid endosymbionts: effects of antibiotic dose and host genotype, and fitness consequences. , 2007, FEMS microbiology ecology.

[80]  B. Currie,et al.  Scabies mite inactivated serine protease paralogues are present both internally in the mite gut and externally in feces. , 2006, The American journal of tropical medicine and hygiene.

[81]  J. Tagg,et al.  Dysgalacticin: a novel, plasmid-encoded antimicrobial protein (bacteriocin) produced by Streptococcus dysgalactiae subsp. equisimilis. , 2006, Microbiology.

[82]  M. Kubo,et al.  Contribution of IL-18 to atopic-dermatitis-like skin inflammation induced by Staphylococcus aureus product in mice. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[83]  L. Arlian,et al.  Presence of Host Immunoglobulin in the Gut of Sarcoptes scabiei (Acari: Sarcoptidae) , 2006, Journal of medical entomology.

[84]  O. Chosidow Clinical practices. Scabies. , 2006, The New England journal of medicine.

[85]  J. Carapetis,et al.  The global burden of group A streptococcal diseases. , 2005, The Lancet. Infectious diseases.

[86]  B. Currie,et al.  Crusted scabies: clinical and immunological findings in seventy-eight patients and a review of the literature. , 2005, The Journal of infection.

[87]  Jun Yu,et al.  VFDB: a reference database for bacterial virulence factors , 2004, Nucleic Acids Res..

[88]  S. Hills,et al.  Control of scabies, skin sores and haematuria in children in the Solomon Islands: another role for ivermectin. , 2005, Bulletin of the World Health Organization.

[89]  T. Foster The Staphylococcus aureus "superbug". , 2004, The Journal of clinical investigation.

[90]  D. Raoult,et al.  Acinetobacter baumannii in Human Body Louse , 2004, Emerging infectious diseases.

[91]  B. Currie,et al.  First documentation of in vivo and in vitro ivermectin resistance in Sarcoptes scabiei. , 2004, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[92]  M. McDonald,et al.  Acute rheumatic fever: a chink in the chain that links the heart to the throat? , 2004, The Lancet. Infectious diseases.

[93]  C. Connors,et al.  Factors supporting sustainability of a community‐based scabies control program , 2002, The Australasian journal of dermatology.

[94]  B. Spratt,et al.  Multilocus sequence typing for characterization of methicillin-resistant and methicillin-susceptible clones of Staphylococcus aureus. , 2000, Journal of clinical microbiology.

[95]  R. Belas,et al.  ZapA, the IgA‐degrading metalloprotease of Proteus mirabilis, is a virulence factor expressed specifically in swarmer cells , 1999, Molecular microbiology.

[96]  T. Pitt,et al.  Distribution of Acinetobacter Species on Skin of Healthy Humans , 1999, European Journal of Clinical Microbiology and Infectious Diseases.

[97]  C. Bandi,et al.  Effects of tetracycline on the filarial worms Brugia pahangi and Dirofilaria immitis and their bacterial endosymbionts Wolbachia. , 1999, International journal for parasitology.

[98]  A. Conde Staphylococcus aureus infections. , 1998, The New England journal of medicine.

[99]  A. Bisno,et al.  Identification of a fibronectin-binding protein (GfbA) in pathogenic group G streptococci , 1996, Infection and immunity.

[100]  N. Anstey,et al.  Community-acquired Acinetobacter pneumonia in the Northern Territory of Australia. , 1992, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[101]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[102]  J. O. Alexander Scabies and pediculosis. , 1968, The Practitioner.

[103]  P. Soulié,et al.  RHEUMATIC HEART DISEASE , 1954, La semaine des hopitaux : organe fonde par l'Association d'enseignement medical des hopitaux de Paris.