4.2 Article

Molecular characteristics of an adhesion molecule containing cholesterol-dependent cytolysin-motif produced by mitis group streptococci

Journal

MICROBIOLOGY AND IMMUNOLOGY
Volume 65, Issue 2, Pages 61-75

Publisher

WILEY
DOI: 10.1111/1348-0421.12868

Keywords

adhesion molecule; cholesterol-dependent cytolysin; Mitis group streptococci; Streptococcus mitis; Streptococcus pseudopneumoniae

Funding

  1. JSPS KAKENHI [15K11012, 18K09552, 18K06764]
  2. Grants-in-Aid for Scientific Research [18K06764, 15K11012, 18K09552] Funding Source: KAKEN

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The study identified a candidate virulence factor named mitilectin (MLC) in Streptococcus pseudopneumoniae, Streptococcus mitis, and Streptococcus pneumoniae, which exhibited lipase activity and human cell-binding activity, serving as an important adhesion molecule for potential pathogenicity.
Streptococcus pseudopneumoniae (SPpn) is a relatively new species closely related to S. pneumoniae (SPn) and S. mitis (SM) belonging to the Mitis group of the genus Streptococcus (MGS). Although genes encoding various pneumococcal virulence factors have been observed in the SPpn genome, the pathogenicity of SPpn against human, including the roles of virulence factor candidates, is still unclear. The present study focused on and characterized a candidate virulence factor previously reported in SPpn with deduced multiple functional domains, such as lipase domain, two lectin domains, and cholesterol-dependent cytolysin-related domain using various recombinant proteins. The gene was found not only in SPpn but also in the strains of SM and SPn. Moreover, the gene product was expressed in the gene-positive strains as secreted and cell-bound forms. The recombinant of gene product showed lipase activity and human cell-binding activity depending on the function of lectin domain(s), but no hemolytic activity. Thus, based on the distribution of the gene within the MGS and its molecular function, the gene product was named mitilectin (MLC) and its contribution to the potential pathogenicity of the MLC-producing strains was investigated. Consequently, the treatment with anti-MLC antibody and the mlc gene-knockout significantly reduced the human cell-binding activity of MLC-producing strains. Therefore, the multifunctional MLC was suggested to be important as an adhesion molecule in considering the potential pathogenicity of the MLC-producing strains belonging to MGS, such as SPpn and SM.

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