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Cryptococcus neoformans phospholipase B1 activates host cell Rac1 for traversal across the blood-brain barrier.

Publication ,  Journal Article
Maruvada, R; Zhu, L; Pearce, D; Zheng, Y; Perfect, J; Kwon-Chung, KJ; Kim, KS
Published in: Cell Microbiol
October 2012

Cryptococcus neoformans penetration into the central nervous system (CNS) requires traversal of the blood-brain barrier that is composed of a single layer of human brain microvascular endothelial cells (HBMEC), but the underlying mechanisms of C. neoformans traversal remain incompletely understood. C. neoformans transcytosis of HBMEC monolayer involves rearrangements of the host cell actin cytoskeleton and small GTP-binding Rho family proteins such as Rac1 are shown to regulate host cell actin cytoskeleton. We, therefore, examined whether C. neoformans traversal of the blood-brain barrier involves host Rac1. While the levels of activated Rac1 (GTP-Rac1) in HBMEC increased significantly upon incubation with C. neoformans strains, pharmacological inhibition and down-modulation of Rac1 significantly decreased C. neoformans transcytosis of HBMEC monolayer. Also, Rac1 inhibition was efficient in preventing C. neoformans penetration into the brain. In addition, C. neoformans phospholipase B1 (Plb1) was shown to contribute to activating host cell Rac1, andSTAT3 was observed to associate with GTP-Rac1 in HBMEC that were incubated with C. neoformans strain but not with its Δplb1 mutant. These findings demonstrate for the first time that C. neoformans Plb1 aids fungal traversal across the blood-brain barrier by activating host cell Rac1 and its association with STAT3, and suggest that pharmacological intervention of host-microbial interaction contributing to traversal of the blood-brain barrier may prevent C. neoformans penetration into the brain.

Duke Scholars

Published In

Cell Microbiol

DOI

EISSN

1462-5822

Publication Date

October 2012

Volume

14

Issue

10

Start / End Page

1544 / 1553

Location

India

Related Subject Headings

  • rac1 GTP-Binding Protein
  • Transcytosis
  • STAT3 Transcription Factor
  • Protein Binding
  • Phospholipases
  • Microbiology
  • Humans
  • Host-Pathogen Interactions
  • Gene Expression Profiling
  • Endothelial Cells
 

Citation

APA
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MLA
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Maruvada, R., Zhu, L., Pearce, D., Zheng, Y., Perfect, J., Kwon-Chung, K. J., & Kim, K. S. (2012). Cryptococcus neoformans phospholipase B1 activates host cell Rac1 for traversal across the blood-brain barrier. Cell Microbiol, 14(10), 1544–1553. https://doi.org/10.1111/j.1462-5822.2012.01819.x
Maruvada, Ravi, Longkun Zhu, Donna Pearce, Yi Zheng, John Perfect, Kyung J. Kwon-Chung, and Kwang Sik Kim. “Cryptococcus neoformans phospholipase B1 activates host cell Rac1 for traversal across the blood-brain barrier.Cell Microbiol 14, no. 10 (October 2012): 1544–53. https://doi.org/10.1111/j.1462-5822.2012.01819.x.
Maruvada R, Zhu L, Pearce D, Zheng Y, Perfect J, Kwon-Chung KJ, et al. Cryptococcus neoformans phospholipase B1 activates host cell Rac1 for traversal across the blood-brain barrier. Cell Microbiol. 2012 Oct;14(10):1544–53.
Maruvada, Ravi, et al. “Cryptococcus neoformans phospholipase B1 activates host cell Rac1 for traversal across the blood-brain barrier.Cell Microbiol, vol. 14, no. 10, Oct. 2012, pp. 1544–53. Pubmed, doi:10.1111/j.1462-5822.2012.01819.x.
Maruvada R, Zhu L, Pearce D, Zheng Y, Perfect J, Kwon-Chung KJ, Kim KS. Cryptococcus neoformans phospholipase B1 activates host cell Rac1 for traversal across the blood-brain barrier. Cell Microbiol. 2012 Oct;14(10):1544–1553.
Journal cover image

Published In

Cell Microbiol

DOI

EISSN

1462-5822

Publication Date

October 2012

Volume

14

Issue

10

Start / End Page

1544 / 1553

Location

India

Related Subject Headings

  • rac1 GTP-Binding Protein
  • Transcytosis
  • STAT3 Transcription Factor
  • Protein Binding
  • Phospholipases
  • Microbiology
  • Humans
  • Host-Pathogen Interactions
  • Gene Expression Profiling
  • Endothelial Cells