Effects of Expression of Streptococcus pneumoniae PspC on the Ability of Streptococcus mitis to Evade Complement-Mediated Immunity
Streptococcus pneumoniae and Streptococcus mitis are genetically closely related and both frequently colonise the naso-oropharynx, yet S. pneumoniae is a common cause of invasive infections whereas S. mitis is only weakly pathogenic. We hypothesise that sensitivity to innate immunity may underlie th...
| 出版年: | Frontiers in Microbiology |
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| 主要な著者: | , , , , |
| フォーマット: | 論文 |
| 言語: | 英語 |
| 出版事項: |
Frontiers Media S.A.
2021-11-01
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| 主題: | |
| オンライン･アクセス: | https://www.frontiersin.org/articles/10.3389/fmicb.2021.773877/full |
| _version_ | 1857130268900458496 |
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| author | Helina Marshall Helina Marshall Ricardo J. José Mogens Kilian Fernanda C. Petersen Jeremy S. Brown |
| author_facet | Helina Marshall Helina Marshall Ricardo J. José Mogens Kilian Fernanda C. Petersen Jeremy S. Brown |
| author_sort | Helina Marshall |
| collection | DOAJ |
| container_title | Frontiers in Microbiology |
| description | Streptococcus pneumoniae and Streptococcus mitis are genetically closely related and both frequently colonise the naso-oropharynx, yet S. pneumoniae is a common cause of invasive infections whereas S. mitis is only weakly pathogenic. We hypothesise that sensitivity to innate immunity may underlie these differences in virulence phenotype. We compared the sensitivity of S. pneumoniae and S. mitis strains to complement-mediated immunity, demonstrating S. mitis strains were susceptible to complement-mediated opsonophagocytosis. S. pneumoniae resistance to complement is partially dependent on binding of the complement regulator Factor H by the surface protein PspC. However, S. mitis was unable to bind factor H. The S. pneumoniae TIGR4 strain pspC was expressed in the S. mitis SK142 strain to create a S. mitis pspC+ strain. Immunoblots demonstrated the S. mitis pspC+ strain expressed PspC, and flow cytometry confirmed this resulted in Factor H binding to S. mitis, reduced susceptibility to complement and improved survival in whole human blood compared to the wild-type S. mitis strain. However, in mouse models the S. mitis pspC+ strain remained unable to establish persistent infection. Unlike S. pneumoniae strains, culture in serum or blood did not support increased CFU of the S. mitis strains. These results suggest S. mitis 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 pspC, poor growth in physiological fluid limited the virulence of S. mitis in mice. |
| format | Article |
| id | doaj-art-4c2e6d5cffa54a548c722c3c4fbd0bd2 |
| institution | Directory of Open Access Journals |
| issn | 1664-302X |
| language | English |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| spelling | doaj-art-4c2e6d5cffa54a548c722c3c4fbd0bd22025-08-19T19:05:50ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2021-11-011210.3389/fmicb.2021.773877773877Effects of Expression of Streptococcus pneumoniae PspC on the Ability of Streptococcus mitis to Evade Complement-Mediated ImmunityHelina Marshall0Helina Marshall1Ricardo J. José2Mogens Kilian3Fernanda C. Petersen4Jeremy S. Brown5Centre for Inflammation and Tissue Repair, UCL Respiratory, Department of Medicine, Royal Free and University College Medical School, University College London, London, United KingdomWellcome-Wolfson Institute for Experimental Medicine, Queen’s University Belfast, Belfast, United KingdomCentre for Inflammation and Tissue Repair, UCL Respiratory, Department of Medicine, Royal Free and University College Medical School, University College London, London, United KingdomDepartment of Biomedicine, Faculty of Health, Aarhus University, Aarhus, DenmarkDepartment of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, NorwayCentre for Inflammation and Tissue Repair, UCL Respiratory, Department of Medicine, Royal Free and University College Medical School, University College London, London, United KingdomStreptococcus pneumoniae and Streptococcus mitis are genetically closely related and both frequently colonise the naso-oropharynx, yet S. pneumoniae is a common cause of invasive infections whereas S. mitis is only weakly pathogenic. We hypothesise that sensitivity to innate immunity may underlie these differences in virulence phenotype. We compared the sensitivity of S. pneumoniae and S. mitis strains to complement-mediated immunity, demonstrating S. mitis strains were susceptible to complement-mediated opsonophagocytosis. S. pneumoniae resistance to complement is partially dependent on binding of the complement regulator Factor H by the surface protein PspC. However, S. mitis was unable to bind factor H. The S. pneumoniae TIGR4 strain pspC was expressed in the S. mitis SK142 strain to create a S. mitis pspC+ strain. Immunoblots demonstrated the S. mitis pspC+ strain expressed PspC, and flow cytometry confirmed this resulted in Factor H binding to S. mitis, reduced susceptibility to complement and improved survival in whole human blood compared to the wild-type S. mitis strain. However, in mouse models the S. mitis pspC+ strain remained unable to establish persistent infection. Unlike S. pneumoniae strains, culture in serum or blood did not support increased CFU of the S. mitis strains. These results suggest S. mitis 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 pspC, poor growth in physiological fluid limited the virulence of S. mitis in mice.https://www.frontiersin.org/articles/10.3389/fmicb.2021.773877/fullStreptococcus pneumoniaeStreptococcus mitisPspCcomplementFactor H |
| spellingShingle | Helina Marshall Helina Marshall Ricardo J. José Mogens Kilian Fernanda C. Petersen Jeremy S. Brown Effects of Expression of Streptococcus pneumoniae PspC on the Ability of Streptococcus mitis to Evade Complement-Mediated Immunity Streptococcus pneumoniae Streptococcus mitis PspC complement Factor H |
| title | Effects of Expression of Streptococcus pneumoniae PspC on the Ability of Streptococcus mitis to Evade Complement-Mediated Immunity |
| title_full | Effects of Expression of Streptococcus pneumoniae PspC on the Ability of Streptococcus mitis to Evade Complement-Mediated Immunity |
| title_fullStr | Effects of Expression of Streptococcus pneumoniae PspC on the Ability of Streptococcus mitis to Evade Complement-Mediated Immunity |
| title_full_unstemmed | Effects of Expression of Streptococcus pneumoniae PspC on the Ability of Streptococcus mitis to Evade Complement-Mediated Immunity |
| title_short | Effects of Expression of Streptococcus pneumoniae PspC on the Ability of Streptococcus mitis to Evade Complement-Mediated Immunity |
| title_sort | effects of expression of streptococcus pneumoniae pspc on the ability of streptococcus mitis to evade complement mediated immunity |
| topic | Streptococcus pneumoniae Streptococcus mitis PspC complement Factor H |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2021.773877/full |
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