The meningococcal vaccine antigen GNA2091 is an analogue of YraP and plays key roles in outer membrane stability and virulence
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Author(s)
Seib, Kate L
Haag, Andreas F
Oriente, Francesca
Fantappie, Laura
Borghi, Sara
Semchenko, Evgeny A
Schulz, Benjamin L
Ferlicca, Francesca
Taddei, Anna Rita
Giuliani, Marzia M
Pizza, Mariagrazia
Delany, Isabel
Year published
2019
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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 ...
View more >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 Δ2091 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 amodel 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.
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View more >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 Δ2091 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 amodel 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.
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Journal Title
FASEB Journal
Volume
33
Issue
11
Copyright Statement
© 2019 Federation of American Societies for Experimental Biology. This is the author-manuscript version of this paper. Reproduced in accordance with the copyright policy of the publisher. Please refer to the journal website for access to the definitive, published version.
Subject
Biochemistry and cell biology
Zoology
Medical physiology
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Biology
Cell Biology