@article{e1804c5bfb444fbbb4b78a83c2847d3e,
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.",
keywords = "Biofilm, Colonization, ECM, M3-type streptococci, Scl1, Scl2, Streptococcus pyogenes",
author = "Bachert, {Beth A.} and Choi, {Soo J.} and LaSala, {Paul R.} and Harper, {Tiffany I.} and McNitt, {Dudley H.} and Boehm, {Dylan T.} and Caswell, {Clayton C.} and Pawel Ciborowski and Keene, {Douglas R.} and Flores, {Anthony R.} and Musser, {James M.} and Flavia Squeglia and Daniela Marasco and Rita Berisio and Slawomir Lukomski",
note = "Funding Information: We thank: Mariette Barbier for assistance with qRT-PCR analysis; Meenal Elliott for assistance with some experiments; Karen Martin, Amanda Ammer, and Lingqing Zhang for assistance with imaging experiments; and Jayme Horning for assistance with mass spectrometry. We thank James Dale for providing anti-M3 antibodies. We also thank Mike Federle and Jennifer Franko for a critical reading of the manuscript. This work was supported in part by National Institutes of Health Grants AI50666 and AI083683 (SL); BB, DHM were supported by the NSF-EPSCoR Graduate Fellowship Program under the Research Infrastructure Improvement (RII) Track-1 award, Cooperative agreement 1003907 (BB) and Integrative Graduate Education and Research Training for Research and Education in Nanotoxicology under award number 1144676 (DHM). BB, DHM were also awarded with the Dr. Jennifer Gossling Scholarship in Microbiology. Flow Cytometry experiments were performed in the West Virginia University Flow Cytometry & Single Cell Core Facility, which is supported by the National Institutes of Health equipment grant numbers S10OD016165 and RR020866 and the Institutional Development Awards (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant numbers P30GM103488 (CoBRE) and P20GM103434 (INBRE). Imaging experiments and image analysis were performed in the West Virginia University Microscope Imaging Facility, which has been supported by the Mary Babb Randolph Cancer Center and NIH grants P20 RR016440, P30 GM103488, and P20 GM103434. Publisher Copyright: {\textcopyright} 2016 Bachert, Choi, LaSala, Harper, McNitt, Boehm, Caswell, Ciborowski, Keene, Flores, Musser, Squeglia, Marasco, Berisio and Lukomski.",
year = "2016",
month = aug,
day = "31",
doi = "10.3389/fcimb.2016.00090",
language = "English (US)",
volume = "6",
journal = "Frontiers in cellular and infection microbiology",
issn = "2235-2988",
publisher = "Frontiers Media S. A.",
number = "AUG",
}