Scholars@Duke publication: Identification of genes from the fungal pathogen Cryptococcus neoformans related to transmigration into the central nervous system.

Identification of genes from the fungal pathogen Cryptococcus neoformans related to transmigration into the central nervous system.

Publication , Journal Article

Tseng, H-K; Liu, C-P; Price, MS; Jong, AY; Chang, J-C; Toffaletti, DL; Betancourt-Quiroz, M; Frazzitta, AE; Cho, W-L; Perfect, JR

Published in: PLoS One

2012

Published version (DOI) Link to item

BACKGROUND: A mouse brain transmigration assessment (MBTA) was created to investigate the central nervous system (CNS) pathogenesis of cryptococcal meningoencephalitis. METHODOLOGY/PRINCIPAL FINDINGS: Two cryptococcal mutants were identified from a pool of 109 pre-selected mutants that were signature-tagged with the nourseothricin acetyltransferase (NAT) resistance cassette. These two mutants displayed abnormal transmigration into the central nervous system. One mutant displaying decreased transmigration contains a null mutation in the putative FNX1 gene, whereas the other mutant possessing a null mutation in the putative RUB1 gene exhibited increased transmigration into the brain. Two macrophage adhesion-defective mutants in the pool, 12F1 and 3C9, showed reduced phagocytosis by macrophages, but displayed no defects in CNS entry suggesting that transit within macrophages (the "Trojan horse" model of CNS entry) is not the primary mechanism for C. neoformans migration into the CNS in this MBTA. CONCLUSIONS/SIGNIFICANCE: This research design provides a new strategy for genetic impact studies on how Cryptococcus passes through the blood-brain barrier (BBB), and the specific isolated mutants in this assay support a transcellular mechanism of CNS entry.

Duke Scholars

Author Dena L. Toffaletti Medicine, Infectious Diseases

Author John Robert Perfect Medicine, Infectious Diseases

Published In

PLoS One

DOI

10.1371/journal.pone.0045083

EISSN

1932-6203

Publication Date

2012

Volume

Issue

Start / End Page

e45083

Location

United States

Related Subject Headings

Transendothelial and Transepithelial Migration
Transcytosis
Temperature
Reproducibility of Results
Polymerase Chain Reaction
Mutation
Models, Biological
Microvessels
Mice
Genetic Testing

Citation

APA

Chicago

ICMJE

MLA

NLM

Tseng, H.-K., Liu, C.-P., Price, M. S., Jong, A. Y., Chang, J.-C., Toffaletti, D. L., … Perfect, J. R. (2012). Identification of genes from the fungal pathogen Cryptococcus neoformans related to transmigration into the central nervous system. PLoS One, 7(9), e45083. https://doi.org/10.1371/journal.pone.0045083

Tseng, Hsiang-Kuang, Chang-Pan Liu, Michael S. Price, Ambrose Y. Jong, Jui-Chih Chang, Dena L. Toffaletti, Marisol Betancourt-Quiroz, Aubrey E. Frazzitta, Wen-Long Cho, and John R. Perfect. “Identification of genes from the fungal pathogen Cryptococcus neoformans related to transmigration into the central nervous system.” PLoS One 7, no. 9 (2012): e45083. https://doi.org/10.1371/journal.pone.0045083.

Tseng H-K, Liu C-P, Price MS, Jong AY, Chang J-C, Toffaletti DL, et al. Identification of genes from the fungal pathogen Cryptococcus neoformans related to transmigration into the central nervous system. PLoS One. 2012;7(9):e45083.

Tseng, Hsiang-Kuang, et al. “Identification of genes from the fungal pathogen Cryptococcus neoformans related to transmigration into the central nervous system.” PLoS One, vol. 7, no. 9, 2012, p. e45083. Pubmed, doi:10.1371/journal.pone.0045083.

Tseng H-K, Liu C-P, Price MS, Jong AY, Chang J-C, Toffaletti DL, Betancourt-Quiroz M, Frazzitta AE, Cho W-L, Perfect JR. Identification of genes from the fungal pathogen Cryptococcus neoformans related to transmigration into the central nervous system. PLoS One. 2012;7(9):e45083.