Mycotoxin Research

, Volume 34, Issue 4, pp 257–268 | Cite as

Gliotoxin penetrates and impairs the integrity of the human blood-brain barrier in vitro

  • Ronak Patel
  • Mohammad Anwar Hossain
  • Nadezhda German
  • Abraham Jacob Al-AhmadEmail author
Original Article


Cerebral fungal infections represent an important public health concern, where a key element of pathophysiology is the ability of the fungi to cross the blood-brain barrier (BBB). Yet the mechanism used by micro-organisms to cross such a barrier and invade the brain parenchyma remains unclear. This study investigated the effects of gliotoxin (GTX), a mycotoxin secreted by Aspergillus fumigatus, on the BBB using brain microvascular endothelial cells (BMECs) derived from induced pluripotent stem cells (iPSCs). We observed that both acute (2 h) and prolonged (24 h) exposure to GTX at the level of 1 μM or higher compromised BMECs monolayer integrity. Notably, acute exposure was sufficient to disrupt the barrier function in iPSC-derived BMECs, resulting in decreased transendothelial electrical resistance (TEER) and increased fluorescein permeability. Further, our data suggest that such disruption occurred without affecting tight junction complexes, via alteration of cell-matrix interactions, alterations in F-actin distribution, through a protein kinase C-independent signaling. In addition to its effect on the barrier function, we have observed a low permeability of GTX across the BBB. This fact can be partially explained by possible interactions of GTX with membrane proteins. Taken together, this study suggests that GTX may contribute in cerebral invasion processes of Aspergillus fumigatus by altering the blood-brain barrier integrity without disrupting tight junction complexes.


Astrocytes Blood-brain barrier Gliotoxin Neurons Stem cells 



Texas Tech University Health Sciences Center institutional funds to N.G. and A.A.


This study was supported by Texas Tech University Health Sciences Center institutional funds to N.G. and A.A.

Compliance with ethical standards

Conflict of interest


Supplementary material

12550_2018_320_MOESM1_ESM.pdf (3 mb)
ESM 1 (PDF 3030 kb)


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Copyright information

© Society for Mycotoxin Research and Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.School of Pharmacy, Department of Pharmaceutical SciencesTexas Tech University Health Sciences CenterAmarilloUSA

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