The meningococcal vaccine antigen GNA2091 is an analogue of YraP and plays key roles in outer membrane stability and virulence.

Autor: Seib KL; Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia., Haag AF; GlaxoSmithKline (GSK) Vaccines, Siena, Italy., Oriente F; GlaxoSmithKline (GSK) Vaccines, Siena, Italy., Fantappiè L; GlaxoSmithKline (GSK) Vaccines, Siena, Italy., Borghi S; GlaxoSmithKline (GSK) Vaccines, Siena, Italy., Semchenko EA; Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia., Schulz BL; School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia., Ferlicca F; GlaxoSmithKline (GSK) Vaccines, Siena, Italy., Taddei AR; Interdepartmental Centre of Electron Microscopy (CIME), Tuscia University, Tuscia, Italy., Giuliani MM; GlaxoSmithKline (GSK) Vaccines, Siena, Italy., Pizza M; GlaxoSmithKline (GSK) Vaccines, Siena, Italy., Delany I; GlaxoSmithKline (GSK) Vaccines, Siena, Italy.
Jazyk: angličtina
Zdroj: FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2019 Nov; Vol. 33 (11), pp. 12324-12335. Date of Electronic Publication: 2019 Aug 23.
DOI: 10.1096/fj.201900669R
Abstrakt: GNA2091 is one of the components of the 4-component meningococcal serogroup B vaccine (4CMenB) vaccine and is highly conserved in all meningococcal strains. However, its functional role has not been fully characterized. Here we show that nmb2091 is part of an operon and is cotranscribed with the nmb2089, nmb2090 , and nmb2092 adjacent genes, and a similar but reduced operon arrangement is conserved in many other gram-negative bacteria. Deletion of the nmb2091 gene causes an aggregative phenotype with a mild defect in cell separation; differences in the outer membrane composition and phospholipid profile, in particular in the phosphoethanolamine levels; an increased level of outer membrane vesicles; and deregulation of the zinc-responsive genes such as znuD . Finally, the ∆2091 strain is attenuated with respect to the wild-type strain in competitive index experiments in the infant rat model of meningococcal infection. Altogether these data suggest that GNA2091 plays important roles in outer membrane architecture, biogenesis, homeostasis, and in meningococcal survival in vivo , and a model for its role is discussed. These findings highlight the importance of GNA2091 as a vaccine component.-Seib, K. L., Haag, A. F., Oriente, F., Fantappiè, L., Borghi, S., Semchenko, E. A., Schulz, B. L., Ferlicca, F., Taddei, A. R., Giuliani, M. M., Pizza, M., Delany, I. The meningococcal vaccine antigen GNA2091 is an analogue of YraP and plays key roles in outer membrane stability and virulence.
Databáze: MEDLINE
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