A genetic screen reveals a periplasmic copper chaperone required for nitrite reductase activity in pathogenic Neisseria

Jen, F.E.- C.; Djoko, K.Y.; Bent, S.J.; Day, C.J.; McEwan, A.G.; Jennings, M.P.

doi:10.1096/fj.15-270751

A genetic screen reveals a periplasmic copper chaperone required for nitrite reductase activity in pathogenic Neisseria

Jen, F.E.- C.; Djoko, K.Y.; Bent, S.J.; Day, C.J.; McEwan, A.G.; Jennings, M.P.

Authors

F.E.- C. Jen

Dr Karrera Djoko karrera.djoko@durham.ac.uk
Associate Professor

S.J. Bent

C.J. Day

A.G. McEwan

M.P. Jennings

Abstract

Under conditions of low oxygen availability, Neisseria meningitidis and Neisseria gonorrhoeae are able to respire via a partial denitrification pathway in which nitrite is converted to nitrous oxide. In this process, nitrite reductase (AniA), a copper (Cu)-containing protein converts nitrite to NO, and this product is converted to nitrous oxide by nitric oxide reductase (NorB). NorB also confers protection against toxic NO, and so we devised a conditional lethal screen, using a norB mutant, to identify mutants that were resistant to nitrite-dependent killing. After random-deletion mutagenesis of N. meningitidis, this genetic screen identified a gene encoding a Cu chaperone that is essential for AniA function, AccA. Purified AccA binds one Cu (I) ion and also possesses a second binding site for Cu (II). This novel periplasmic Cu chaperone (AccA) appears to be essential for provision of Cu ions to AniA of pathogenic Neisseria to generate an active nitrite reductase. Apart from the Neisseria genus, AccA is distributed across a wide range of environmental Proteobacteria species.—Jen, F. E.-C., Djoko, K. Y., Bent, S. J., Day, C. J., McEwan, A. G., Jennings, M. P. A genetic screen reveals a periplasmic copper chaperone required for nitrite reductase activity in pathogenic Neisseria.

Citation

Jen, F. C., Djoko, K., Bent, S., Day, C., McEwan, A., & Jennings, M. (2015). A genetic screen reveals a periplasmic copper chaperone required for nitrite reductase activity in pathogenic Neisseria. FASEB Journal, 29(9), 3828-3838. https://doi.org/10.1096/fj.15-270751

Journal Article Type	Article
Acceptance Date	May 18, 2015
Online Publication Date	Jun 1, 2015
Publication Date	2015-09
Deposit Date	Sep 6, 2017
Journal	FASEB Journal
Print ISSN	0892-6638
Electronic ISSN	1530-6860
Publisher	Federation of American Society of Experimental Biology (FASEB)
Peer Reviewed	Peer Reviewed
Volume	29
Issue	9
Pages	3828-3838
DOI	https://doi.org/10.1096/fj.15-270751
Public URL	https://durham-repository.worktribe.com/output/1350037