Effects of Streptococcus Pneumoniae Strain Background on Complement Resistance

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2011 Oct 25

PMID 22022358

Citations 17

Authors

Catherine Hyams

Sophia Opel

William Hanage

Jose Yuste

Katie Bax

Birgitta Henriques-Normark

Brian G Spratt

Jeremy S Brown

Affiliations

Soon will be listed here.

Abstract

Background: Immunity to infections caused by Streptococcus pneumoniae is dependent on complement. There are wide variations in sensitivity to complement between S. pneumoniae strains that could affect their ability to cause invasive infections. Although capsular serotype is one important factor causing differences in complement resistance between strains, there is also considerable other genetic variation between S. pneumoniae strains that may affect complement-mediated immunity. We have therefore investigated whether genetically distinct S. pneumoniae strains with the same capsular serotype vary in their sensitivity to complement mediated immunity.

Methodology And Principal Findings: C3b/iC3b deposition and neutrophil association were measured using flow cytometry assays for S. pneumoniae strains with different genetic backgrounds for each of eight capsular serotypes. For some capsular serotypes there was marked variation in C3b/iC3b deposition between different strains that was independent of capsule thickness and correlated closely to susceptibility to neutrophil association. C3b/iC3b deposition results also correlated weakly with the degree of IgG binding to each strain. However, the binding of C1q (the first component of the classical pathway) correlated more closely with C3b/iC3b deposition, and large differences remained in complement sensitivity between strains with the same capsular serotype in sera in which IgG had been cleaved with IdeS.

Conclusions: These data demonstrate that bacterial factors independent of the capsule and recognition by IgG have strong effects on the susceptibility of S. pneumoniae to complement, and could therefore potentially account for some of the differences in virulence between strains.

Citing Articles

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Phillips Z, Trappetti C, Van Den Bergh A, Martin G, Calcutt A, Ozberk V Microbiol Spectr. 2022; 10(3):e0091622.

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References

Kim J, Weiser J . Association of intrastrain phase variation in quantity of capsular polysaccharide and teichoic acid with the virulence of Streptococcus pneumoniae. J Infect Dis. 1998; 177(2):368-77. DOI: 10.1086/514205. View

Yuste J, Khandavilli S, Ansari N, Muttardi K, Ismail L, Hyams C . The effects of PspC on complement-mediated immunity to Streptococcus pneumoniae vary with strain background and capsular serotype. Infect Immun. 2009; 78(1):283-92. PMC: 2798213. DOI: 10.1128/IAI.00541-09. View

Angel C, Ruzek M, Hostetter M . Degradation of C3 by Streptococcus pneumoniae. J Infect Dis. 1994; 170(3):600-8. DOI: 10.1093/infdis/170.3.600. View

Brown J, Hussell T, Gilliland S, Holden D, Paton J, Ehrenstein M . The classical pathway is the dominant complement pathway required for innate immunity to Streptococcus pneumoniae infection in mice. Proc Natl Acad Sci U S A. 2002; 99(26):16969-74. PMC: 139253. DOI: 10.1073/pnas.012669199. View

Yuste J, Sen A, Truedsson L, Jonsson G, Tay L, Hyams C . Impaired opsonization with C3b and phagocytosis of Streptococcus pneumoniae in sera from subjects with defects in the classical complement pathway. Infect Immun. 2008; 76(8):3761-70. PMC: 2493217. DOI: 10.1128/IAI.00291-08. View

Ogunniyi A, Grabowicz M, Mahdi L, Cook J, Gordon D, Sadlon T . Pneumococcal histidine triad proteins are regulated by the Zn2+-dependent repressor AdcR and inhibit complement deposition through the recruitment of complement factor H. FASEB J. 2008; 23(3):731-8. DOI: 10.1096/fj.08-119537. View

Hollingshead S, Becker R, Briles D . Diversity of PspA: mosaic genes and evidence for past recombination in Streptococcus pneumoniae. Infect Immun. 2000; 68(10):5889-900. PMC: 101551. DOI: 10.1128/IAI.68.10.5889-5900.2000. View

Dave S, Pangburn M, Pruitt C, McDaniel L . Interaction of human factor H with PspC of Streptococcus pneumoniae. Indian J Med Res. 2004; 119 Suppl:66-73. View

Ren B, McCrory M, Pass C, Bullard D, Ballantyne C, Xu Y . The virulence function of Streptococcus pneumoniae surface protein A involves inhibition of complement activation and impairment of complement receptor-mediated protection. J Immunol. 2004; 173(12):7506-12. DOI: 10.4049/jimmunol.173.12.7506. View

10.

Iannelli F, Oggioni M, Pozzi G . Allelic variation in the highly polymorphic locus pspC of Streptococcus pneumoniae. Gene. 2002; 284(1-2):63-71. DOI: 10.1016/s0378-1119(01)00896-4. View

11.

Sandgren A, Sjostrom K, Olsson-Liljequist B, Christensson B, Samuelsson A, Kronvall G . Effect of clonal and serotype-specific properties on the invasive capacity of Streptococcus pneumoniae. J Infect Dis. 2004; 189(5):785-96. DOI: 10.1086/381686. View

12.

Melin M, Trzcinski K, Meri S, Kayhty H, Vakevainen M . The capsular serotype of Streptococcus pneumoniae is more important than the genetic background for resistance to complement. Infect Immun. 2010; 78(12):5262-70. PMC: 2981297. DOI: 10.1128/IAI.00740-10. View

13.

Hammerschmidt S, Wolff S, Hocke A, Rosseau S, Muller E, Rohde M . Illustration of pneumococcal polysaccharide capsule during adherence and invasion of epithelial cells. Infect Immun. 2005; 73(8):4653-67. PMC: 1201225. DOI: 10.1128/IAI.73.8.4653-4667.2005. View

14.

Hyams C, Camberlein E, Cohen J, Bax K, Brown J . The Streptococcus pneumoniae capsule inhibits complement activity and neutrophil phagocytosis by multiple mechanisms. Infect Immun. 2009; 78(2):704-15. PMC: 2812187. DOI: 10.1128/IAI.00881-09. View

15.

Tettelin H, Nelson K, Paulsen I, Eisen J, Read T, Peterson S . Complete genome sequence of a virulent isolate of Streptococcus pneumoniae. Science. 2001; 293(5529):498-506. DOI: 10.1126/science.1061217. View

16.

Yuste J, Botto M, Bottoms S, Brown J . Serum amyloid P aids complement-mediated immunity to Streptococcus pneumoniae. PLoS Pathog. 2007; 3(9):1208-19. PMC: 1971117. DOI: 10.1371/journal.ppat.0030120. View

17.

Sleeman K, Griffiths D, Shackley F, Diggle L, Gupta S, Maiden M . Capsular serotype-specific attack rates and duration of carriage of Streptococcus pneumoniae in a population of children. J Infect Dis. 2006; 194(5):682-8. DOI: 10.1086/505710. View

18.

Hiller N, Janto B, Hogg J, Boissy R, Yu S, Powell E . Comparative genomic analyses of seventeen Streptococcus pneumoniae strains: insights into the pneumococcal supragenome. J Bacteriol. 2007; 189(22):8186-95. PMC: 2168654. DOI: 10.1128/JB.00690-07. View

19.

Yuste J, Botto M, Paton J, Holden D, Brown J . Additive inhibition of complement deposition by pneumolysin and PspA facilitates Streptococcus pneumoniae septicemia. J Immunol. 2005; 175(3):1813-9. DOI: 10.4049/jimmunol.175.3.1813. View

20.

Segal A, Jones O . Absence of cytochrome b reduction in stimulated neutrophils from both female and male patients with chronic granulomatous disease. FEBS Lett. 1980; 110(1):111-4. DOI: 10.1016/0014-5793(80)80035-4. View