title: Variable expression of immunoreactive surface proteins of Propionibacterium acnes.
abstract: Despite accumulating data implicating Propionibacterium acnes in a variety of diseases, its precise role in infection remains to be determined. P. acnes antigen-specific CD4(+) T cells are present in early inflamed acne lesions and may be involved in the inflammatory response; however, little is known about the specific antigens involved. In this study, B cell and T cell antigens from P. acnes expression libraries were cloned and evaluated and the four predominant proteins identified were investigated. Two of these antigens share some homology with an M-like protein of Streptococcus equi and have dermatan-sulphate-binding activity (PA-25957 and 5541). The remaining two antigens, PA-21693 and 4687, are similar to the product of the Corynebacterium diphtheriae htaA gene from the hmu ABC transport locus, although only one of these (PA-21693) is encoded within an hmu-like operon and conserved amongst a range of clinical isolates. All four proteins contain an LPXTG motif, although only PA-21693 contains a characteristic sortase-sorting signal. Variation in the expression of PA-4687, 25957 and 5541 is evident amongst clinical isolates and is generated both by frameshifts associated with the putative signal peptide and by variable numbers of repeat regions toward the carboxy-terminus, potentially generating heterogeneity of molecular mass and antigenic variation. In addition, in the case of PA-25957, a frameshift in a C-rich region at the extreme carboxy-terminus eliminates the LPXTG motif in some isolates. For the dermatan-sulphate-binding PA-25957, IgG1 antibody in serum from acne-positive donors was shown to be specific for the amino-terminal region of the protein, which also contains a CD4(+) T cell epitope. In contrast, serum from acne-negative donors shows an IgG2 and IgG3 antibody subclass response to the carboxy-terminal region. These data have implications for the potential role of P. acnes in inflammatory acne and other diseases.
authors.affiliation: Corixa Corporation, Infectious Disease Research Institute, Seattle, WA 98101, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lodes
authors.affiliation: Corixa Corporation, Infectious Disease Research Institute, Seattle, WA 98101, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Secrist
authors.affiliation: Corixa Corporation, Infectious Disease Research Institute, Seattle, WA 98101, USA.
authors.forename: Darin R
authors.initials: DR
authors.lastname: Benson
authors.affiliation: Corixa Corporation, Infectious Disease Research Institute, Seattle, WA 98101, USA.
authors.forename: Shyian
authors.initials: S
authors.lastname: Jen
authors.affiliation: Corixa Corporation, Infectious Disease Research Institute, Seattle, WA 98101, USA.
authors.forename: Kurt D
authors.initials: KD
authors.lastname: Shanebeck
authors.affiliation: Corixa Corporation, Infectious Disease Research Institute, Seattle, WA 98101, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Guderian
authors.affiliation: Corixa Corporation, Infectious Disease Research Institute, Seattle, WA 98101, USA.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Maisonneuve
authors.affiliation: Corixa Corporation, Infectious Disease Research Institute, Seattle, WA 98101, USA.
authors.forename: Ajay
authors.initials: A
authors.lastname: Bhatia
authors.affiliation: Corixa Corporation, Infectious Disease Research Institute, Seattle, WA 98101, USA.
authors.forename: David
authors.initials: D
authors.lastname: Persing
authors.affiliation: Microbiology Building, School of Medicine and Dentistry, Queen's University Belfast, Grosvenor Road, Belfast BT12 6BN, UK.
authors.forename: Sheila
authors.initials: S
authors.lastname: Patrick
authors.affiliation: Corixa Corporation, Infectious Disease Research Institute, Seattle, WA 98101, USA.
authors.forename: Yasir A W
authors.initials: YAW
authors.lastname: Skeiky
mesh_terms: D000152:Acne Vulgaris / Q000276:immunology*; D000595:Amino Acid Sequence; D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics; D003001:Cloning, Molecular; D017124:Conserved Sequence; D003353:Corynebacterium diphtheriae / Q000235:genetics; D003871:Dermatan Sulfate / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D016368:Frameshift Mutation; D015870:Gene Expression; D014644:Genetic Variation; D006801:Humans; D015151:Immunoblotting; D007074:Immunoglobulin G / Q000276:immunology; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D011425:Propionibacterium acnes / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D011485:Protein Binding; D021382:Protein Sorting Signals / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D018502:Streptococcus equi / Q000235:genetics
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D018984:Epitopes, T-Lymphocyte; D007074:Immunoglobulin G; D008565:Membrane Proteins; D021382:Protein Sorting Signals; C014689:streptococcal M protein; D003871:Dermatan Sulfate