In vitro expression of vital virulent genes of clinical and environmental isolates of Cryptococcus neoformans/gattii in endothelial cells of human blood-brain barrier
Abstract
Background Evaluation of the pathogenesis of clinical and environmental cryptococcal isolates to the central nervous system is necessary for understanding the risk. This study was designed to determine the in vitro expression of six important virulent genes of Cryptococcus neoformans/gattii in Human Brain Microvascular Endothelial cells (hBMEC).Methods The hBMEC were infected with Cryptococcus to determine invasion and survival rate at 3, 12 and 24hours by subsequent colony count of internalized yeasts. The whole RNA of the intracellular Cryptococcus was extracted to quantify the expression of CAP10, PLB1, ENA1, URE1, LAC1, and MATα genes by real-time quantitative PCR for 3 and 12hours of infection.Results Invasion and survival rates were higher in clinical and standard strains of C. neoformans. A significant difference was observed among the clinical and environmental isolates for the expression of CAP10, ENA1, LAC1, MATα and URE1 at 3hours, and ENA1, LAC1, MATα, PLB1 and URE1 at 12hours. Clinical isolates showed significant upregulation of all the genes except PLB1, which was higher in environmental isolates. Relative expressions at the two time-points showed statistically significant (P=0.043) changes for the clinical isolates and no significance (P=0.063) for environmental isolates.Conclusion The C. gattii (VGI) isolates showed significantly lower invasion and survival than C. neoformans (VNI, and VNII) irrespective of their sources. Clinical isolates exhibited higher expression for the majority of the virulent genes until 12hours of infection, probably due to their better adaptation in the host system and enhanced pathogenicity than the environmental counterparts.
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Melanin is produced by laccases, which are upregulated in C. neoformans clinical and environmental isolates.
“Melanin is produced by laccases, which are upregulated in C. neoformans clinical and environmental isolates66”
From Treatment strategies for cryptococcal infection: challenges, advances and future outlook (2021) · cites this paper as [66]
Cites
Olszewski, M. A., Noverr, M. C., Chen, G.-H., Toews, G. B., Cox, G. M., Perfect, J. R., & Huffnagle, G. B. (2004) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63734-0 · Cited by 292 · see citing works
Chang, Y. C., Stins, M. F., McCaffery, M. J., Miller, G., Pare, D. R., Dam, T., Paul-Satyasee, M., Kim, K. S., & Kwon-Chung, K. J. (2004) · Infection and Immunity · doi:10.1128/iai.72.9.4985-4995.2004 · Cited by 275 · see citing works
Shi, M., Li, S. S., Zheng, C., Jones, G. J., Kim, K. S., Zhou, H., Kubes, P., & Mody, C. H. (2010) · Journal of Clinical Investigation · doi:10.1172/jci41963 · Cited by 222 · see citing works
Chen, S. H. M., Stins, M. F., Huang, S.-H., Chen, Y. H., Kwon-Chung, K. J., Chang, Y., Kim, K. S., Suzuki, K., & Jong, A. Y. (2003) · Journal of Medical Microbiology · doi:10.1099/jmm.0.05230-0 · Cited by 189 · see citing works
Cryptococcus neoformansGene Expression during Murine Macrophage Infection
Fan, W., Kraus, P. R., Boily, M.-J., & Heitman, J. (2005) · Eukaryotic Cell · doi:10.1128/ec.4.8.1420-1433.2005 · Cited by 186 · see citing works
Bacterial induction of Snail1 contributes to blood-brain barrier disruption
Kim, B. J., Hancock, B. M., Bermudez, A., Cid, N. D., Reyes, E., van Sorge, N. M., Lauth, X., Smurthwaite, C. A., Hilton, B. J., Stotland, A., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci74159 · Cited by 145 · see citing works
Self-citationNielsen, K., Cox, G. M., Litvintseva, A. P., Mylonakis, E. E., Malliaris, S. D., Benjamin, D. K., Giles, S. S., Mitchell, T. G., Casadevall, A., Perfect, J. R., et al. (2005) · Infection and Immunity · doi:10.1128/iai.73.8.4922-4933.2005 · Cited by 139 · see citing works
Jong, A., Wu, C.-H., Chen, H.-M., Luo, F., Kwon-Chung, K. J., Chang, Y. C., LaMunyon, C. W., Plaas, A., & Huang, S.-H. (2007) · Eukaryotic Cell · doi:10.1128/ec.00120-07 · Cited by 113 · see citing works
Djordjevic, J. T. (2010) · Frontiers in Microbiology · doi:10.3389/fmicb.2010.00125 · Cited by 102 · see citing works
Nichols, C. B., Fraser, J. A., & Heitman, J. (2004) · Molecular Biology of the Cell · doi:10.1091/mbc.e04-05-0370 · Cited by 86 · see citing works
Mechanisms of Infection by the Human Fungal Pathogen Cryptococcus Neoformans
Sabiiti, W., & May, R. C. (2012) · Future Microbiology · doi:10.2217/fmb.12.102 · Cited by 81 · see citing works
Idnurm, A., Walton, F. J., Floyd, A. M., Reedy, J. L., & Heitman, J. (2009) · Eukaryotic Cell · doi:10.1128/ec.00375-08 · Cited by 80 · see citing works
Litvintseva, A. P., & Mitchell, T. G. (2009) · Infection and Immunity · doi:10.1128/iai.00296-09 · Cited by 75 · see citing works
Huang, S.-H., Long, M., Wu, C.-H., Kwon-Chung, K. J., Chang, Y. C., Chi, F., Lee, S., & Jong, A. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.219378 · Cited by 69 · see citing works
Ngamskulrungroj, P., Price, J. L., Sorrell, T. C., Perfect, J. R., & Meyer, W. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016076 · Cited by 63 · see citing works
Paradoxical roles of alveolar macrophages in the host response to Cryptococcus neoformans
McQuiston, T. J., & Williamson, P. R. (2011) · Journal of Infection and Chemotherapy · doi:10.1007/s10156-011-0306-2 · Cited by 61 · see citing works
Huffnagle, G. B., & McNeil, L. K. (1999) · Journal of NeuroVirology · doi:10.3109/13550289909029748 · Cited by 60 · see citing works
Maruvada, R., & Kim, K. S. (2012) · Infection and Immunity · doi:10.1128/iai.06320-11 · Cited by 41 · see citing works
Thompson, G. R., Albert, N. D., Hodge, G., Wilson, M., Sykes, J. E., Bays, D. J., Firacative, C., Meyer, W., & Kontoyiannis, D. P. (2014) · Infection and Immunity · doi:10.1128/iai.01805-14 · Cited by 40 · see citing works
Isolation and characterisation of the phospholipase B gene ofCryptococcus neoformansvar.gattii
Latouche, G. N., Sorrell, T. C., & Meyer, W. (2002) · FEMS Yeast Research · doi:10.1111/j.1567-1364.2002.tb00122.x · Cited by 30 · see citing works
The Triple Threat of Cryptococcosis: It’s the Body Site, the Strain, and/or the Host
Perfect, J. R. (2012) · mBio · doi:10.1128/mbio.00165-12 · Cited by 29 · see citing works
Movahed, E., Munusamy, K., Tan, G. M. Y., Looi, C. Y., Tay, S. T., & Wong, W. F. (2015) · PLoS ONE · doi:10.1371/journal.pone.0137457 · Cited by 18 · see citing works
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Treatment strategies for cryptococcal infection: challenges, advances and future outlook
Iyer, K. R., Revie, N. M., Fu, C., Robbins, N., & Cowen, L. E. (2021) · Nature Reviews Microbiology · doi:10.1038/s41579-021-00511-0 · Cited by 363 · see citing works
In vitroinfection models to study fungal–host interactions
Last, A., Maurer, M., Mosig, A. S., Gresnigt, M. S., & Hube, B. (2021) · FEMS Microbiology Reviews · doi:10.1093/femsre/fuab005 · Cited by 43 · see citing works
Al-Huthaifi, A. M., Radman, B. A., Al-Alawi, A. A., Mahmood, F., & Liu, T. (2024) · Journal of Fungi · doi:10.3390/jof10080586 · Cited by 35 · see citing works
Krishnan, P., Udupi, G. A., Santhoshkumar, R., V., M. M., B, V. K. H., Netravathi, & Nagarathna, S. (2026) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2026.1735570
- Authors
- Lahiri, S., Banerjee, A., Bhutda, S., Palaniappan, M., Bahubali, V. H., Manjunath, N., Maji, S., & Siddaiah, N.
- Affiliations
- National Institute of Mental Health and Neurosciences (IN)
- Indian Institute of Technology Bombay (IN)
- Corresponding author
- Siddaiah, N.
- Venue
- Journal de Mycologie Médicale
- Publisher
- Elsevier BV
- Published
- 2019-09
- Volume
- 29
- Issue
- 3
- Pages
- 239-244
- ISSN
- 1156-5233 (ISSN-L)
- OpenAlex
- W2949427287
- Cited by
- 4
- References
- 22
- Citations by year
- 2026: 1 · 2024: 1 · 2021: 2
- FWCI
- 0.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal de Mycologie Médicale (publishedVersion)
- PubMed (publishedVersion)
- DSpace (IIT Bombay) (submittedVersion)
- Funders
- University Grants Commission (2121130717, 18-12/2011)
- Topics
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Life Sciences › Immunology and Microbiology › Microbiology › Bacterial Infections and Vaccines
- Life Sciences › Immunology and Microbiology › Parasitology › Parasitic Infections and Diagnostics
- Keywords
- Cryptococcus neoformans, Cryptococcus gattii, virulence genes, gene expression, human brain microvascular endothelial cells, blood-brain barrier, clinical isolates, environmental isolates, PLB1, ENA1, cryptococcal meningitis, pathogenesis
- MeSH terms
- Host Microbial Interactions, Blood-Brain Barrier, Cell Line, Cryptococcosis, Cryptococcus neoformans, Environmental Microbiology, Fungal Proteins, Genotype, Humans, Gene Expression, Virulence Factors, Endothelial Cells, Cryptococcus gattii
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