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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Helina Marshall, Ricardo J. José, Mogens Kilian, Fernanda C. Petersen, Jeremy S. Brown
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	Streptococcus pneumoniae Streptococcus mitis PspC complement Factor H Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/4c2e6d5cffa54a548c722c3c4fbd0bd2
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:4c2e6d5cffa54a548c722c3c4fbd0bd2
record_format	dspace
spelling	oai:doaj.org-article:4c2e6d5cffa54a548c722c3c4fbd0bd22021-11-22T07:21:07ZEffects of Expression of Streptococcus pneumoniae PspC on the Ability of Streptococcus mitis to Evade Complement-Mediated Immunity1664-302X10.3389/fmicb.2021.773877https://doaj.org/article/4c2e6d5cffa54a548c722c3c4fbd0bd22021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmicb.2021.773877/fullhttps://doaj.org/toc/1664-302XStreptococcus 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.Helina MarshallHelina MarshallRicardo J. JoséMogens KilianFernanda C. PetersenJeremy S. BrownFrontiers Media S.A.articleStreptococcus pneumoniaeStreptococcus mitisPspCcomplementFactor HMicrobiologyQR1-502ENFrontiers in Microbiology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Streptococcus pneumoniae Streptococcus mitis PspC complement Factor H Microbiology QR1-502
spellingShingle	Streptococcus pneumoniae Streptococcus mitis PspC complement Factor H Microbiology QR1-502 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
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
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
title	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_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_sort	effects of expression of streptococcus pneumoniae pspc on the ability of streptococcus mitis to evade complement-mediated immunity
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/4c2e6d5cffa54a548c722c3c4fbd0bd2
work_keys_str_mv	AT helinamarshall effectsofexpressionofstreptococcuspneumoniaepspcontheabilityofstreptococcusmitistoevadecomplementmediatedimmunity AT helinamarshall effectsofexpressionofstreptococcuspneumoniaepspcontheabilityofstreptococcusmitistoevadecomplementmediatedimmunity AT ricardojjose effectsofexpressionofstreptococcuspneumoniaepspcontheabilityofstreptococcusmitistoevadecomplementmediatedimmunity AT mogenskilian effectsofexpressionofstreptococcuspneumoniaepspcontheabilityofstreptococcusmitistoevadecomplementmediatedimmunity AT fernandacpetersen effectsofexpressionofstreptococcuspneumoniaepspcontheabilityofstreptococcusmitistoevadecomplementmediatedimmunity AT jeremysbrown effectsofexpressionofstreptococcuspneumoniaepspcontheabilityofstreptococcusmitistoevadecomplementmediatedimmunity
_version_	1718417853245292544

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

Ejemplares similares