title: Functional characteristics of the Staphylococcus aureus δ-toxin allelic variant G10S.
abstract: Staphylococcus aureus δ-toxin is a member of the phenol-soluble modulin (PSM) peptide family. PSMs have multiple functions in staphylococcal pathogenesis; for example, they lyse red and white blood cells and trigger inflammatory responses. Compared to other PSMs, δ-toxin is usually more strongly expressed but has only moderate cytolytic capacities. The amino acid sequences of S. aureus PSMs are well conserved with two exceptions, one of which is the δ-toxin allelic variant G10S. This variant is a characteristic of the subspecies S. argenteus and S. aureus sequence types ST1 and ST59, the latter representing the most frequent cause of community-associated infections in Asia. δ-toxin G10S and strains expressing that variant from plasmids or the genome had significantly reduced cytolytic and pro-inflammatory capacities, including in a strain background with pronounced production of other PSMs. However, in murine infection models, isogenic strains expressing the two δ-toxin variants did not cause measurable differences in disease severity. Our findings indicate that the widespread G10S allelic variation of the δ-toxin locus has a significant impact on key pathogenesis mechanisms, but more potent members of the PSM peptide family may overshadow that impact in vivo.
authors.affiliation: Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, The National Institutes of Health, Bethesda, MD 20892, United States of America.
authors.forename: Gordon Y C
authors.initials: GY
authors.lastname: Cheung
authors.affiliation: Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, The National Institutes of Health, Bethesda, MD 20892, United States of America.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Yeh
authors.affiliation: Cellular and Molecular Microbiology Division, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen 72076, Germany.
authors.forename: Dorothee
authors.initials: D
authors.lastname: Kretschmer
authors.affiliation: Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, The National Institutes of Health, Bethesda, MD 20892, United States of America.
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Duong
authors.affiliation: Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, The National Institutes of Health, Bethesda, MD 20892, United States of America.
authors.forename: Kwame
authors.initials: K
authors.lastname: Tuffuor
authors.affiliation: Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, The National Institutes of Health, Bethesda, MD 20892, United States of America.
authors.forename: Chih-Lung
authors.initials: CL
authors.lastname: Fu
authors.affiliation: Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, The National Institutes of Health, Bethesda, MD 20892, United States of America.
authors.forename: Hwang-Soo
authors.initials: HS
authors.lastname: Joo
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of California, San Francisco, San Francisco, CA 94110, United States of America.
authors.forename: Binh A
authors.initials: BA
authors.lastname: Diep
authors.affiliation: Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Dermatology, Chiba University Graduate School of Medicine, Chiba 2608670, Japan.
authors.forename: Yuumi
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, United States of America.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Nunez
authors.affiliation: Cellular and Molecular Microbiology Division, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen 72076, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Peschel
authors.affiliation: Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, The National Institutes of Health, Bethesda, MD 20892, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Otto
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D001427:Bacterial Toxins / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D051379:Mice; D010957:Plasmids / Q000235:genetics; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; C025971:staphylococcal delta toxin