title: Unique Footprint in the scl1.3 Locus Affects Adhesion and Biofilm Formation of the Invasive M3-Type Group A Streptococcus.
abstract: The streptococcal collagen-like proteins 1 and 2 (Scl1 and Scl2) are major surface adhesins that are ubiquitous among group A Streptococcus (GAS). Invasive M3-type strains, however, have evolved two unique conserved features in the scl1 locus: (i) an IS1548 element insertion in the scl1 promoter region and (ii) a nonsense mutation within the scl1 coding sequence. The scl1 transcript is drastically reduced in M3-type GAS, contrasting with a high transcription level of scl1 allele in invasive M1-type GAS. This leads to a lack of Scl1 expression in M3 strains. In contrast, while scl2 transcription and Scl2 production are elevated in M3 strains, M1 GAS lack Scl2 surface expression. M3-type strains were shown to have reduced biofilm formation on inanimate surfaces coated with cellular fibronectin and laminin, and in human skin equivalents. Repair of the nonsense mutation and restoration of Scl1 expression on M3-GAS cells, restores biofilm formation on cellular fibronectin and laminin coatings. Inactivation of scl1 in biofilm-capable M28 and M41 strains results in larger skin lesions in a mouse model, indicating that lack of Scl1 adhesin promotes bacterial spread over localized infection. These studies suggest the uniquely evolved scl1 locus in the M3-type strains, which prevents surface expression of the major Scl1 adhesin, contributed to the emergence of the invasive M3-type strains. Furthermore these studies provide insight into the molecular mechanisms mediating colonization, biofilm formation, and pathogenesis of group A streptococci.
authors.affiliation: Department of Microbiology, Immunology, and Cell Biology, West Virginia University Morgantown, WV, USA.
authors.forename: Beth A
authors.initials: BA
authors.lastname: Bachert
authors.affiliation: Department of Microbiology, Immunology, and Cell Biology, West Virginia University Morgantown, WV, USA.
authors.forename: Soo J
authors.initials: SJ
authors.lastname: Choi
authors.affiliation: Department of Pathology, West Virginia University Morgantown, WV, USA.
authors.forename: Paul R
authors.initials: PR
authors.lastname: LaSala
authors.affiliation: Department of Pathology, West Virginia University Morgantown, WV, USA.
authors.forename: Tiffany I
authors.initials: TI
authors.lastname: Harper
authors.affiliation: Department of Microbiology, Immunology, and Cell Biology, West Virginia University Morgantown, WV, USA.
authors.forename: Dudley H
authors.initials: DH
authors.lastname: McNitt
authors.affiliation: Department of Microbiology, Immunology, and Cell Biology, West Virginia University Morgantown, WV, USA.
authors.forename: Dylan T
authors.initials: DT
authors.lastname: Boehm
authors.affiliation: Department of Microbiology, Immunology, and Cell Biology, West Virginia University Morgantown, WV, USA.
authors.forename: Clayton C
authors.initials: CC
authors.lastname: Caswell
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center Omaha, NE, USA.
authors.forename: Pawel
authors.initials: P
authors.lastname: Ciborowski
authors.affiliation: Shriners Hospital for Children Portland, OR, USA.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Keene
authors.affiliation: Section of Infectious Diseases, Department of Pediatrics, Baylor College of Medicine, Texas Children's HospitalHouston, TX, USA; Department of Pathology and Genomic Medicine, Center for Molecular and Translational Human Infectious Diseases Research, Houston Methodist Research Institute and Hospital SystemHouston, TX, USA.
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Flores
authors.affiliation: Department of Pathology and Genomic Medicine, Center for Molecular and Translational Human Infectious Diseases Research, Houston Methodist Research Institute and Hospital System Houston, TX, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Musser
authors.affiliation: Institute of Biostructures and Bioimaging, National Research Council Naples, Italy.
authors.forename: Flavia
authors.initials: F
authors.lastname: Squeglia
authors.affiliation: Department of Pharmacy, University of Naples Frederico II Naples, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Marasco
authors.affiliation: Institute of Biostructures and Bioimaging, National Research Council Naples, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Berisio
authors.affiliation: Department of Microbiology, Immunology, and Cell Biology, West Virginia University Morgantown, WV, USA.
authors.forename: Slawomir
authors.initials: S
authors.lastname: Lukomski
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics; D001422:Bacterial Adhesion; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D018441:Biofilms / Q000254:growth & development*; D002352:Carrier Proteins / Q000235:genetics; D003094:Collagen / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005816:Genetic Complementation Test; D056426:Genetic Loci; D006801:Humans; D051379:Mice; D065288:Serogroup; D013290:Streptococcal Infections / Q000382:microbiology / Q000473:pathology; D013297:Streptococcus pyogenes / Q000145:classification / Q000235:genetics* / Q000502:physiology*
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; C423454:Scl1 protein, Streptococcus; C014689:streptococcal M protein; D003094:Collagen
keywords: ECM; M3-type streptococci; Scl1; Scl2; Streptococcus pyogenes; biofilm; colonization