Evidence map›Paper›PMID 22646320›Full record

ArticleCellular microbiology2012

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

Ravi Maruvada, Longkun Zhu, Donna Pearce, Yi Zheng, John Perfect, Kyung J Kwon-Chung, Kwang Sik Kim

Open access · bronzeAbstract read
In one paragraph

Article in Cellular microbiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
3.3field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

50 citing papers in PubMed, 77 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Frontiers in immunology · 2025
    Article
  6. Article
  7. Article
  8. Mechanisms and Virulence Factors ofJournal of fungi (Basel, Switzerland) · 2024
    Review
  9. Review
  10. Measuring Urease and Phospholipase Secretion in Cryptococcus neoformans.Methods in molecular biology (Clifton, N.J.) · 2024
    Article
  11. Article
  12. Macropinocytosis as a potential mechanism driving neurotropism ofFrontiers in cellular and infection microbiology · 2023
    Review
  13. Extension ofmBio · 2022
    Article
  14. Article
  15. Journal of fungi (Basel, Switzerland) · 2022
    Review
  16. Review
  17. Neuroprotective effects of CysLTR antagonist onExperimental and therapeutic medicine · 2022
    Article
  18. Article
  19. Macrophage Mediated Immunomodulation DuringFrontiers in cellular and infection microbiology · 2022
    Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 5 institutions in 1 country.

Ravi MaruvadaDepartment of Pediatrics, Division of Pediatric Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Longkun Zhu
Donna Pearce
Yi Zheng
John Perfect
Kyung J Kwon-Chung
Kwang Sik Kim
Johns Hopkins University · USCincinnati Children's Hospital Medical Center · USDuke Medical Center · USJohns Hopkins Medicine · USNational Institute of Allergy and Infectious Diseases · US

Funding

PATHOGENESIS OF NEONATAL MENINGITISR01NS026310 · NINDS · JOHNS HOPKINS UNIVERSITY · PI KIM, KWANG S · 1988 to 2008
$3.6M
Mechanism of Brain Invasion by Cryptococcus neoformansZIAAI000057 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI KWON-CHUNG, KYUNG · 2009 to 2017
$2.1M
Leukotrienes and blood-brain barrierR01AI084984 · NIAID · JOHNS HOPKINS UNIVERSITY · PI KIM, KWANG S · 2010 to 2014
$2.0M
E. coli invasion of brain endothelial cellsR56NS026310 · NINDS · JOHNS HOPKINS UNIVERSITY · PI KIM, KWANG S · 2009 to 2009
$410k
Intramural NIH HHS ZIA AI000057NIAID NIH HHS AI84984NIAID NIH HHS R01 AI084984NINDS NIH HHS NS26310NINDS NIH HHS R01 NS026310NINDS NIH HHS R56 NS026310
6 · The paper itself

Abstract

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.

Indexed as

Host-Pathogen InteractionsBlood-Brain BarrierCell LineCryptococcus neoformansEndothelial CellsGene Expression ProfilingHumansPhospholipasesProtein Bindingrac1 GTP-Binding ProteinSTAT3 Transcription FactorTranscytosisPhospholipasesrac1 GTP-Binding ProteinRAC1 protein, humanSTAT3 protein, humanSTAT3 Transcription Factor

Identifiers

PMID22646320
PMCPMC3443264
OpenAlexW1581896553

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.