The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
The surface-anchored NanA protein promotes pneumococcal brain endothelial cell invasion
Open accessAbstract
In humans, Streptococcus pneumoniae (SPN) is the leading cause of bacterial meningitis, a disease with high attributable mortality and frequent permanent neurological sequelae. The molecular mechanisms underlying the central nervous system tropism of SPN are incompletely understood, but include a primary interaction of the pathogen with the blood–brain barrier (BBB) endothelium. All SPN strains possess a gene encoding the surface-anchored sialidase (neuraminidase) NanA, which cleaves sialic acid on host cells and proteins. Here, we use an isogenic SPN NanA-deficient mutant and heterologous expression of the protein to show that NanA is both necessary and sufficient to promote SPN adherence to and invasion of human brain microvascular endothelial cells (hBMECs). NanA-mediated hBMEC invasion depends only partially on sialidase activity, whereas the N-terminal lectinlike domain of the protein plays a critical role. NanA promotes SPN–BBB interaction in a murine infection model, identifying the protein as proximal mediator of CNS entry by the pathogen.
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Cites
Clinical features and prognostic factors in adults with bacterial meningitis
van de Beek, D., de Gans, J., Spanjaard, L., Weisfelt, M., Reitsma, J. B., & Vermeulen, M. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa040845 · Cited by 1,639
Orihuela, C. J., Mahdavi, J., Thornton, J., Mann, B., Wooldridge, K. G., Abouseada, N., Oldfield, N. J., Self, T., Ala’Aldeen, D. A. A., & Tuomanen, E. I. (2009) · Journal of Clinical Investigation · doi:10.1172/jci36759 · Cited by 303
Doran, K. S., Engelson, E. J., Khosravi, A., Maisey, H. C., Fedtke, I., Equils, O., Michelsen, K. S., Arditi, M., Peschel, A., & Nizet, V. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23829 · Cited by 231
Self-citationCrennell, S., Garman, E., Laver, G., Vimr, E., & Taylor, G. (1994) · Structure · doi:10.1016/s0969-2126(00)00053-8 · Cited by 205
Cited by
The blood-brain barrier: an engineering perspective
Wong, A. D., Ye, M., Levy, A. F., Rothstein, J. D., Bergles, D. E., & Searson, P. C. (2013) · Frontiers in Neuroengineering · doi:10.3389/fneng.2013.00007 · Cited by 662
Dando, S. J., Mackay-Sim, A., Norton, R., Currie, B. J., St. John, J. A., Ekberg, J. A. K., Batzloff, M., Ulett, G. C., & Beacham, I. R. (2014) · Clinical Microbiology Reviews · doi:10.1128/cmr.00118-13 · Cited by 428
The Pneumococcus: Epidemiology, Microbiology, and Pathogenesis
Henriques-Normark, B., & Tuomanen, E. I. (2013) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a010215 · Cited by 411
Microbiota and the gut-brain-axis: Implications for new therapeutic design in the CNS
Liu, L., Huh, J. R., & Shah, K. (2022) · eBioMedicine · doi:10.1016/j.ebiom.2022.103908 · Cited by 344
Community-acquired bacterial meningitis
van de Beek, D., Brouwer, M., Hasbun, R., Koedel, U., Whitney, C. G., & Wijdicks, E. (2016) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2016.74 · Cited by 312
Metadata
- Authors
- Uchiyama, S., Carlin, A. F., Khosravi, A., Weiman, S., Banerjee, A., Quach, D., Hightower, G., Mitchell, T. J., Doran, K. S., & Nizet, V.
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2009-08-17
- Volume
- 206
- Issue
- 9
- Pages
- 1845-1852
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2111965293
- Cited by
- 184
- References
- 4
- FWCI
- 12.61
- Type
- journal article
- Language
- en
- Open access
- green
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- Uchiyama, S., Carlin, A. F., Khosravi, A., Weiman, S., Banerjee, A., Quach, D., Hightower, G., Mitchell, T. J., Doran, K. S., & Nizet, V. (2009). The surface-anchored NanA protein promotes pneumococcal brain endothelial cell invasion. Journal of Experimental Medicine. https://doi.org/10.1084/jem.20090386
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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