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The meningococcal vaccine antigen GNA2091 is an analogue of YraP and plays key roles in outer membrane stability and virulence
Author(s) -
Seib Kate L.,
Haag Andreas F.,
Oriente Francesca,
Fantappiè Laura,
Borghi Sara,
Semchenko Evgeny A.,
Schulz Benjamin L.,
Ferlicca Francesca,
Taddei Anna Rita,
Giuliani Marzia M.,
Pizza Mariagrazia,
Delany Isabel
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201900669r
Subject(s) - operon , virulence , bacterial outer membrane , microbiology and biotechnology , meningococcal vaccine , biology , neisseria meningitidis , antigen , biogenesis , gene , strain (injury) , regulon , bacteria , genetics , escherichia coli , anatomy
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. FASEB J. 33, 12324‐12335 (2019). www.fasebj.org