Comprehensive Genomic Characterization of Staphylococcus aureus Isolated from Atopic Dermatitis Patients in Japan: Correlations with Disease Severity, Eruption Type, and Anatomical Site
ABSTRACT Atopic dermatitis (AD) shows frequent recurrence. Staphylococcus aureus is the primary microbial component in AD and is associated with disease activity. However, traditional typing methods have failed to characterize virulent AD isolates at the clone level. We conducted a comprehensive gen...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2023-08-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.05239-22 |
| _version_ | 1797741792726089728 |
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| author | Shoko Obata Junzo Hisatsune Hiroshi Kawasaki Ayano Fukushima-Nomura Tamotsu Ebihara Chika Arai Kanako Masuda Shoko Kutsuno Yasuhisa Iwao Motoyuki Sugai Masayuki Amagai Keiji Tanese |
| author_facet | Shoko Obata Junzo Hisatsune Hiroshi Kawasaki Ayano Fukushima-Nomura Tamotsu Ebihara Chika Arai Kanako Masuda Shoko Kutsuno Yasuhisa Iwao Motoyuki Sugai Masayuki Amagai Keiji Tanese |
| author_sort | Shoko Obata |
| collection | DOAJ |
| description | ABSTRACT Atopic dermatitis (AD) shows frequent recurrence. Staphylococcus aureus is the primary microbial component in AD and is associated with disease activity. However, traditional typing methods have failed to characterize virulent AD isolates at the clone level. We conducted a comprehensive genomic characterization of S. aureus strains isolated from the skin of AD patients and healthy donors, comparing the whole-genome sequences of the 261 isolates with anatomical and lesional (AD-A)/nonlesional (AD-NL)/healthy sites, eruption types, clinical scores, virulence, and antimicrobial resistance gene repertoires in Japan. Sequence type (ST) diversity was lost with worsening disease activity; ST188 was the most frequently detected ST in AD-A and had the strongest correlation with AD according to the culture rate and proportion with worsening disease activity. ST188 and ST20 isolates inhabited all skin conditions, with significantly higher proportions in AD skin than in healthy skin. ST8, ST15, and ST5 proportions were equivalent for all skin conditions; ST30 was detected only in healthy skin; and ST12 was detected only in AD skin. ST97 detected in AD-A and healthy skin was clearly branched into two subclades, designated ST97A and ST97H. A comparison of two genomes led to the discovery that only ST97A possessed the complete trp operon, enabling bacterial survival without exogenous tryptophan (Trp) on AD skin, where the Trp level was significantly reduced. Primary STs showing an AD skin inhabitation trend (ST188, ST97A, ST20, and ST12) were all trp operon positive. The predominant clones (ST188 and ST97) possessed almost no enterotoxin genes, no mecA gene, and few other antimicrobial resistance genes, different from the trend observed in Europe/North America. IMPORTANCE While Staphylococcus aureus is a member of the normal human skin flora, its strong association with the onset of atopic dermatitis (AD) has been suggested. However, previous studies failed to assign specific clones relevant to disease activities. Enterotoxins produced by S. aureus have been suggested to aggravate and exacerbate the inflammation of AD skin, but their role remains ambiguous. We conducted a nuanced comprehensive characterization of isolates from AD patients and healthy donors, comparing the whole-genome sequences of the isolates with anatomical and lesional/nonlesional/healthy sites, eruption types, clinical scores, virulence, and antimicrobial resistance gene repertoires in Japan. We demonstrate that specific clones are associated with disease severity and clinical manifestations, and the dominant clones are devoid of enterotoxin genes and antimicrobial resistance genes. These findings undermine the established notion of the pathophysiological function of S. aureus associated with AD and introduce a new concept of S. aureus colonization in AD. |
| first_indexed | 2024-03-12T14:31:48Z |
| format | Article |
| id | doaj.art-d520f3a6c4e14dcc864ca9dd61e48f56 |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-03-12T14:31:48Z |
| publishDate | 2023-08-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-d520f3a6c4e14dcc864ca9dd61e48f562023-08-17T13:04:14ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972023-08-0111410.1128/spectrum.05239-22Comprehensive Genomic Characterization of Staphylococcus aureus Isolated from Atopic Dermatitis Patients in Japan: Correlations with Disease Severity, Eruption Type, and Anatomical SiteShoko Obata0Junzo Hisatsune1Hiroshi Kawasaki2Ayano Fukushima-Nomura3Tamotsu Ebihara4Chika Arai5Kanako Masuda6Shoko Kutsuno7Yasuhisa Iwao8Motoyuki Sugai9Masayuki Amagai10Keiji Tanese11Department of Dermatology, Keio University School of Medicine, Tokyo, JapanAntimicrobial Resistance Research Center, National Institute of Infectious Diseases, Tokyo, JapanDepartment of Dermatology, Keio University School of Medicine, Tokyo, JapanDepartment of Dermatology, Keio University School of Medicine, Tokyo, JapanDepartment of Dermatology, Keio University School of Medicine, Tokyo, JapanDepartment of Antimicrobial Resistance, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, JapanDepartment of Antimicrobial Resistance, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, JapanAntimicrobial Resistance Research Center, National Institute of Infectious Diseases, Tokyo, JapanAntimicrobial Resistance Research Center, National Institute of Infectious Diseases, Tokyo, JapanAntimicrobial Resistance Research Center, National Institute of Infectious Diseases, Tokyo, JapanDepartment of Dermatology, Keio University School of Medicine, Tokyo, JapanDepartment of Dermatology, Keio University School of Medicine, Tokyo, JapanABSTRACT Atopic dermatitis (AD) shows frequent recurrence. Staphylococcus aureus is the primary microbial component in AD and is associated with disease activity. However, traditional typing methods have failed to characterize virulent AD isolates at the clone level. We conducted a comprehensive genomic characterization of S. aureus strains isolated from the skin of AD patients and healthy donors, comparing the whole-genome sequences of the 261 isolates with anatomical and lesional (AD-A)/nonlesional (AD-NL)/healthy sites, eruption types, clinical scores, virulence, and antimicrobial resistance gene repertoires in Japan. Sequence type (ST) diversity was lost with worsening disease activity; ST188 was the most frequently detected ST in AD-A and had the strongest correlation with AD according to the culture rate and proportion with worsening disease activity. ST188 and ST20 isolates inhabited all skin conditions, with significantly higher proportions in AD skin than in healthy skin. ST8, ST15, and ST5 proportions were equivalent for all skin conditions; ST30 was detected only in healthy skin; and ST12 was detected only in AD skin. ST97 detected in AD-A and healthy skin was clearly branched into two subclades, designated ST97A and ST97H. A comparison of two genomes led to the discovery that only ST97A possessed the complete trp operon, enabling bacterial survival without exogenous tryptophan (Trp) on AD skin, where the Trp level was significantly reduced. Primary STs showing an AD skin inhabitation trend (ST188, ST97A, ST20, and ST12) were all trp operon positive. The predominant clones (ST188 and ST97) possessed almost no enterotoxin genes, no mecA gene, and few other antimicrobial resistance genes, different from the trend observed in Europe/North America. IMPORTANCE While Staphylococcus aureus is a member of the normal human skin flora, its strong association with the onset of atopic dermatitis (AD) has been suggested. However, previous studies failed to assign specific clones relevant to disease activities. Enterotoxins produced by S. aureus have been suggested to aggravate and exacerbate the inflammation of AD skin, but their role remains ambiguous. We conducted a nuanced comprehensive characterization of isolates from AD patients and healthy donors, comparing the whole-genome sequences of the isolates with anatomical and lesional/nonlesional/healthy sites, eruption types, clinical scores, virulence, and antimicrobial resistance gene repertoires in Japan. We demonstrate that specific clones are associated with disease severity and clinical manifestations, and the dominant clones are devoid of enterotoxin genes and antimicrobial resistance genes. These findings undermine the established notion of the pathophysiological function of S. aureus associated with AD and introduce a new concept of S. aureus colonization in AD.https://journals.asm.org/doi/10.1128/spectrum.05239-22atopic dermatitisglabellabackcubital fossavolar forearmSCORAD |
| spellingShingle | Shoko Obata Junzo Hisatsune Hiroshi Kawasaki Ayano Fukushima-Nomura Tamotsu Ebihara Chika Arai Kanako Masuda Shoko Kutsuno Yasuhisa Iwao Motoyuki Sugai Masayuki Amagai Keiji Tanese Comprehensive Genomic Characterization of Staphylococcus aureus Isolated from Atopic Dermatitis Patients in Japan: Correlations with Disease Severity, Eruption Type, and Anatomical Site Microbiology Spectrum atopic dermatitis glabella back cubital fossa volar forearm SCORAD |
| title | Comprehensive Genomic Characterization of Staphylococcus aureus Isolated from Atopic Dermatitis Patients in Japan: Correlations with Disease Severity, Eruption Type, and Anatomical Site |
| title_full | Comprehensive Genomic Characterization of Staphylococcus aureus Isolated from Atopic Dermatitis Patients in Japan: Correlations with Disease Severity, Eruption Type, and Anatomical Site |
| title_fullStr | Comprehensive Genomic Characterization of Staphylococcus aureus Isolated from Atopic Dermatitis Patients in Japan: Correlations with Disease Severity, Eruption Type, and Anatomical Site |
| title_full_unstemmed | Comprehensive Genomic Characterization of Staphylococcus aureus Isolated from Atopic Dermatitis Patients in Japan: Correlations with Disease Severity, Eruption Type, and Anatomical Site |
| title_short | Comprehensive Genomic Characterization of Staphylococcus aureus Isolated from Atopic Dermatitis Patients in Japan: Correlations with Disease Severity, Eruption Type, and Anatomical Site |
| title_sort | comprehensive genomic characterization of staphylococcus aureus isolated from atopic dermatitis patients in japan correlations with disease severity eruption type and anatomical site |
| topic | atopic dermatitis glabella back cubital fossa volar forearm SCORAD |
| url | https://journals.asm.org/doi/10.1128/spectrum.05239-22 |
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