TY - JOUR
T1 - Meningococcal virulence in zebrafish embryos depends on capsule polysaccharide structure
AU - Schipper, Kim
AU - Preusting, Lisanne C.
AU - van Sorge, Nina M.
AU - Pannekoek, Yvonne
AU - van der Ende, Arie
N1 - Funding Information: Funding for this investigator-initiated research was provided by a grant from Pfizer: WI242174. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. All authors declare no other competing interests. Publisher Copyright: Copyright © 2022 Schipper, Preusting, van Sorge, Pannekoek and van der Ende.
PY - 2022/9/23
Y1 - 2022/9/23
N2 - Neisseria meningitidis or the meningococcus, can cause devasting diseases such as sepsis and meningitis. Its polysaccharide capsule, on which serogrouping is based, is the most important virulence factor. Non-encapsulated meningococci only rarely cause disease, due to their sensitivity to the host complement system. How the capsular polysaccharide structure of N. meningitidis relates to virulence is largely unknown. Meningococcal virulence can be modeled in zebrafish embryos as the innate immune system of the zebrafish embryo resembles that of mammals and is fully functional two days post-fertilization. In contrast, the adaptive immune system does not develop before 4 weeks post-fertilization. We generated isogenic meningococcal serogroup variants to study how the chemical composition of the polysaccharide capsule affects N. meningitidis virulence in the zebrafish embryo model. H44/76 serogroup B killed zebrafish embryos in a dose-dependent manner, whereas the non-encapsulated variant was completely avirulent. Neutrophil depletion was observed after infection with encapsulated H44/76, but not with its non-encapsulated variant HB-1. The survival of embryos infected with isogenic capsule variants of H44/76 was capsule specific. The amount of neutrophil depletion differed accordingly. Both embryo killing capacity and neutrophil depletion after infection correlated with the number of carbons used per repeat unit of the capsule polysaccharide during its biosynthesis (indicative of metabolic cost). Conclusion: Meningococcal virulence in the zebrafish embryo largely depends on the presence of the polysaccharide capsule but the extent of the contribution is determined by its structure. The observed differences between the meningococcal isogenic capsule variants in zebrafish embryo virulence may depend on differences in metabolic cost.
AB - Neisseria meningitidis or the meningococcus, can cause devasting diseases such as sepsis and meningitis. Its polysaccharide capsule, on which serogrouping is based, is the most important virulence factor. Non-encapsulated meningococci only rarely cause disease, due to their sensitivity to the host complement system. How the capsular polysaccharide structure of N. meningitidis relates to virulence is largely unknown. Meningococcal virulence can be modeled in zebrafish embryos as the innate immune system of the zebrafish embryo resembles that of mammals and is fully functional two days post-fertilization. In contrast, the adaptive immune system does not develop before 4 weeks post-fertilization. We generated isogenic meningococcal serogroup variants to study how the chemical composition of the polysaccharide capsule affects N. meningitidis virulence in the zebrafish embryo model. H44/76 serogroup B killed zebrafish embryos in a dose-dependent manner, whereas the non-encapsulated variant was completely avirulent. Neutrophil depletion was observed after infection with encapsulated H44/76, but not with its non-encapsulated variant HB-1. The survival of embryos infected with isogenic capsule variants of H44/76 was capsule specific. The amount of neutrophil depletion differed accordingly. Both embryo killing capacity and neutrophil depletion after infection correlated with the number of carbons used per repeat unit of the capsule polysaccharide during its biosynthesis (indicative of metabolic cost). Conclusion: Meningococcal virulence in the zebrafish embryo largely depends on the presence of the polysaccharide capsule but the extent of the contribution is determined by its structure. The observed differences between the meningococcal isogenic capsule variants in zebrafish embryo virulence may depend on differences in metabolic cost.
KW - Neisseria meningitidis
KW - innate immunity
KW - isogenic capsule variants
KW - meningococcal polysaccharide capsule
KW - zebrafish embryo infection
UR - http://www.scopus.com/inward/record.url?scp=85139445326&partnerID=8YFLogxK
U2 - https://doi.org/10.3389/fcimb.2022.1020201
DO - https://doi.org/10.3389/fcimb.2022.1020201
M3 - Article
C2 - 36211969
SN - 2235-2988
VL - 12
SP - 1020201
JO - Frontiers in cellular and infection microbiology
JF - Frontiers in cellular and infection microbiology
M1 - 1020201
ER -