Dufailu, Osman ORCID: 0000-0002-8291-9832, Mahdavi, Jafar, Ala'Aldeen, Dlawer A.A., Wooldridge, Karl G. and Oldfield, Neil J. (2018) Uptake of Neisserial autotransporter lipoprotein (NalP) promotes an increase in human brain microvascular endothelial cell metabolic activity. Microbial Pathogenesis, 124. pp. 70-75. ISSN 0882-4010 (Print), 1096-1208 (Online) (doi:https://doi.org/10.1016/j.micpath.2018.08.001)

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Abstract

Neisseria meningitidis is normally a human nasopharyngeal commensal but is also capable of causing lifethreatening sepsis and meningitis. N. meningitidis secretes several virulence-associated proteins including Neisserial autotransporter lipoprotein (NalP), an immunogenic, type Va autotransporter harboring an S8-family serine endopeptidase domain. NalP has been previously characterized as a cell-surface maturation protease which processes other virulence-associated meningococcal surface proteins, and as a factor contributing to the survival of meningococci in human serum due to its ability to cleave complement factor C3. Here, recombinant NalP (rNalP) fragments were purified and used to investigate the interaction of NalP with host cells. Flow cytometry and confocal microscopy demonstrated binding and uptake of rNalP into different human cell types. High-resolution microscopy confirmed that internalized rNalP predominantly localized to the perinuclear region of cells. Abolition of rNalP protease activity using site-directed mutagenesis did not influence uptake or subcellular localization, but inactive rNalP (rNalPS426A) was unable to induce an increase in human brain microvascular endothelial cell metabolic activity provoked by proteolytically-active rNalP. Our data suggests a more complex and multifaceted role for NalP in meningococcal pathogenesis than was previously understood which includes novel intra-host cell functions.

Item Type:	Article
Uncontrolled Keywords:	Neisseria meningitidis; autotransporter; NalP; cellular uptake; pathogenesis; proteolysis
Subjects:	Q Science > Q Science (General) Q Science > QR Microbiology > QR180 Immunology
Faculty / School / Research Centre / Research Group:	Faculty of Engineering & Science Faculty of Engineering & Science > School of Science (SCI)
Last Modified:	07 Nov 2023 10:14
URI:	http://gala.gre.ac.uk/id/eprint/35982

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