The Pneumococcal Serine-Rich Repeat Protein Is an Intra-Species Bacterial Adhesin That Promotes Bacterial Aggregation In Vivo and in Biofilms

PLoS Pathogens

Karin Sauer¹  Pooja Shivshankar²  Samuel Trakhtenbroit²  Carlos J. Orihuela²  Carlos J. Sanchez²  Paul M. Sullam³  Peter W. M. Hermans⁴  Kim Stol⁴ 

[1] Department of Biological Sciences, Binghamton University, Binghamton, New York, United States of America;Department of Microbiology and Immunology, The University of Texas Health Science Center San Antonio, San Antonio, Texas, United States of America;Division of Infectious Diseases, San Francisco VA Medical Center and the University of California, San Francisco, California, United States of America;Laboratory of Pediatric Infectious Diseases, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

关键词: Bacterial biofilms;    Pneumococcus;    Bacteria;    Staphylococcus aureus;    Biofilms;    Antibodies;    Immune serum;    Recombinant proteins;   

DOI  :  10.1371/journal.ppat.1001044

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The Pneumococcal serine-rich repeat protein (PsrP) is a pathogenicity island encoded adhesin that has been positively correlated with the ability of Streptococcus pneumoniae to cause invasive disease. Previous studies have shown that PsrP mediates bacterial attachment to Keratin 10 (K10) on the surface of lung cells through amino acids 273–341 located in the Basic Region (BR) domain. In this study we determined that the BR domain of PsrP also mediates an intra-species interaction that promotes the formation of large bacterial aggregates in the nasopharynx and lungs of infected mice as well as in continuous flow-through models of mature biofilms. Using numerous methods, including complementation of mutants with BR domain deficient constructs, fluorescent microscopy with Cy3-labeled recombinant (r)BR, Far Western blotting of bacterial lysates, co-immunoprecipitation with rBR, and growth of biofilms in the presence of antibodies and competitive peptides, we determined that the BR domain, in particular amino acids 122–166 of PsrP, promoted bacterial aggregation and that antibodies against the BR domain were neutralizing. Using similar methodologies, we also determined that SraP and GspB, the Serine-rich repeat proteins (SRRPs) of Staphylococcus aureus and Streptococcus gordonii, respectively, also promoted bacterial aggregation and that their Non-repeat domains bound to their respective SRRPs. This is the first report to show the presence of biofilm-like structures in the lungs of animals infected with S. pneumoniae and show that SRRPs have dual roles as host and bacterial adhesins. These studies suggest that recombinant Non-repeat domains of SRRPs (i.e. BR for S. pneumoniae) may be useful as vaccine antigens to protect against Gram-positive bacteria that cause infection.

【 授权许可】

CC BY