AUTHOR=Marshall Helina , José Ricardo J. , Kilian Mogens , Petersen Fernanda C. , Brown Jeremy S. 

TITLE=Effects of Expression of Streptococcus pneumoniae PspC on the Ability of Streptococcus mitis to Evade Complement-Mediated Immunity

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.773877

DOI=10.3389/fmicb.2021.773877

ISSN=1664-302X

ABSTRACT=<p><italic>Streptococcus pneumoniae</italic> and <italic>Streptococcus mitis</italic> are genetically closely related and both frequently colonise the naso-oropharynx, yet <italic>S. pneumoniae</italic> is a common cause of invasive infections whereas <italic>S. mitis</italic> is only weakly pathogenic. We hypothesise that sensitivity to innate immunity may underlie these differences in virulence phenotype. We compared the sensitivity of <italic>S. pneumoniae</italic> and <italic>S. mitis</italic> strains to complement-mediated immunity, demonstrating <italic>S. mitis</italic> strains were susceptible to complement-mediated opsonophagocytosis. <italic>S. pneumoniae</italic> resistance to complement is partially dependent on binding of the complement regulator Factor H by the surface protein PspC. However, <italic>S. mitis</italic> was unable to bind factor H. The <italic>S. pneumoniae</italic> TIGR4 strain <italic>pspC</italic> was expressed in the <italic>S. mitis</italic> SK142 strain to create a <italic>S. mitis pspC<sup>+</sup></italic> strain. Immunoblots demonstrated the <italic>S. mitis pspC<sup>+</sup></italic> strain expressed PspC, and flow cytometry confirmed this resulted in Factor H binding to <italic>S. mitis</italic>, reduced susceptibility to complement and improved survival in whole human blood compared to the wild-type <italic>S. mitis</italic> strain. However, in mouse models the <italic>S. mitis pspC<sup>+</sup></italic> strain remained unable to establish persistent infection. Unlike <italic>S. pneumoniae</italic> strains, culture in serum or blood did not support increased CFU of the <italic>S. mitis</italic> strains. These results suggest <italic>S. mitis</italic> is highly sensitive to opsonisation with complement partially due to an inability to bind Factor H, but even when complement sensitivity was reduced by expression of <italic>pspC</italic>, poor growth in physiological fluid limited the virulence of <italic>S. mitis</italic> in mice.</p>