The Carter Lab
Fungal Pathogens and Treatment Strategies
School of Life and Environmental Sciences
University of Sydney
Fungal Pathogens
The morphological plasticity of Cryptococcus
Normal and micro-cells of Cryptococcus
Cryptococcus is a yeast pathogen that is normally found in the environment but can be inhaled and cause lung infection. In rare cases, or when the host is immunosuppressed, it can also travel to the brain, resulting in meningitis that is fatal without treatment. Cryptococcus is widely represented as a spherical encapsulated yeast but it can display considerable heterogeneity in shape and size, with giant, micro- and irregular shaped cells seen in vitro and during infection. The following recent papers from our lab explore these different cell types in Cryptococcus neoformans and Cryptococcus gattii species complexes:
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Fernandes, K.E., Fraser, J.A. and Carter, D.A. (2022) Lineages derived from Cryptococcus neoformans type strain H99 support a link between the capacity to be pleomorphic and virulence. mBio 13:2 https://doi.org/10.1128/mbio.00283-22
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Fernandes, K.E. and Carter, D.A. (2020) Cellular plasticity of pathogenic fungi during infection. PLoS Pathog 16(6): e1008571. https://doi.org/10.1371/journal.ppat.1008571
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Fernandes, K.E., Brockway, A., Haverkamp, M., Cuomo, C.A., Van Ogtrop, F., Perfect, J.R. and Carter, D.A. (2018) Phenotypic variability correlates with clinical outcome in Cryptococcus isolates obtained from Botswanan HIV/AIDS patients. mBio 9 (5), e02016-18. DOI: 10.1128/mBio.02016-18
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Fernandes, K., Dwyer, C., Campbell, L.T. and Carter, D.A. (2016) Species in the Cryptococcus gattii complex differ in capsule and cell size following growth under capsule-inducing conditions. mSphere 1(6):e00350-16. doi:10.1128/mSphere.00350-16. doi: 10.1128/mSphere.00350-16
The ecology of fungal pathogens and drivers of drug resistance
Cryptococcus is found in the environment in association with decaying wood - in Australia this is often from Eucalyptus trees
Aspergillus species produce vast quantities of hydrophobic spores that readily spread in the environment and in susceptible people and animals can cause infections
Opportunistic pathogens like Cryptococcus and Aspergillus are predominantly environmental saprotrophs, with infection of animals and people likely to be "accidental". As such, their lifestyle in the environment is important for determining their interactions with us and the likelihood of disease. Furthermore, our use of fungicidal agents could influence their capacity to develop antifungal resistance and compromise our ability to treat infections. In these papers we explore the interface between ecology and infection in fungal pathogens:
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Nnadi, N.E and Carter, D.A. (2021) Climate change and the emergence of fungal pathogens. PLoS Pathogens. 17(4): e1009503. https://doi.org/10.1371/journal.ppat.1009503
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Carneiro, H.C.S., Bastos, R.W., Ribeiro, N.Q., Gouveia-Eufrasio, L., Costa, M.C., Magalhães, T.F.F., Oliveira, L.V., Paixão, T.A., Joffe, L.S., Rodrigues, M.L., de Sousa Araújo, G.R., Frases, S., Ruiz, J.C., Marinho, P., Abrahão, J.S., Resende-Stoianoff, M.A., Carter, D., Santos, D.A. (2020) Hypervirulence and cross-resistance to a clinical antifungal are induced by an environmental fungicide in Cryptococcus gattii. Science of the Total Environment 140135. https://doi.org/10.1016/j.scitotenv.2020.140135
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Hainsworth, S., Hubka, V., Lawrie, A.C., Carter, D., Vanniasinkam, T., Grando, D. (2020) Predominance of Trichophyton interdigitale revealed in podiatric nail dust collections in Eastern Australia. Mycopathologia, 185:175-185
https://doi.org/10.1007/s11046-019-00363-6
Talbot, J.J., Subedi, S., Halliday, C.L., Hibbs, D.E., Lai, F., Lopez-Ruiz, F.J., Harper, L. Park, R.F., Cuddy, W.S., Biswas, C., Cooley, L., Carter, D., Sorrell, T.C., Barrs, V.R. & Chen, S C-A (2018). Surveillance for azole resistance in clinical and environmental isolates of Aspergillus fumigatus in Australia and cyp51A homology modelling of azole-resistant isolates. Journal of Antimicrobial Chemotherapy. https://doi.org/10.1093/jac/dky187
Billmyre, R.B., Croll, D., Li, W., Mieczkowski, P., Carter D.A., Cuomo, C.A., Kronstad, J.W. and Heitman, J. (2014) Highly recombinant VGII Cryptococcus gattii population develops clonal outbreak clusters through both sexual macroevolution and asexual microevolution. mBio 5: e01494–01414. DOI: https://doi.org/10.1128/mBio.01494-14
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Dehghan, P., Bui, T., Campbell, L.T., Lai, Y-W., Tran-Dinh, N., Zaini, F and Carter, D.A. (2014) Multilocus variable-number tandem-repeat analysis of clinical isolates of Aspergillus flavus from Iran reveals the first cases of Aspergillus minisclerotigenes associated with human infection. BMC Infectious Diseases 14:358. DOI: 10.1186/1471-2334-14-358
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Byrnes, E. J., III, W. Li, Y. Lewit, H. Ma, K. Voelz, P. Ren, D. A. Carter, V. Chaturvedi, R. J. Bildfell, R. C. May, and J. Heitman. (2010) Emergence and pathogenicity of highly virulent Cryptococcus gattii genotypes in the Northwest United States. PLoS Pathogens 6:e1000850. https://doi.org/10.1371/journal.ppat.1000850
Tran-Dinh, N, Kennedy, I, Bui, T and Carter, D. (2009) Survey of Vietnamese peanuts, corn and soil for the presence of Aspergillus flavus and Aspergillus parasiticus (2009) Mycopathologia 168:257–268. https://doi.org/10.1007/s11046-009-9221-9
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Bui, T., Lin, X., Malik, R., Heitman, J. and Carter, D. (2008) Isolates of Cryptococcus neoformans from infected animals reveal genetic exchange in unisexual, a mating type populations. Eukaryotic Cell 7: 1771–1780. doi: 10.1128/EC.00097-08
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Saul, N., Krockenberger, M. and Carter, D.A. (2008) Evidence of recombination in mixed mating type and a-only populations of Cryptococcus gattii sourced from single Eucalyptus tree hollows. Eukaryotic Cell 7: 727–734. doi: 10.1128/EC.00020-08
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Campbell, L.T., Currie, B.J., Krockenberger, M. Malik, R., Meyer, W., Heitman, J. and Carter, D.A. (2005) Clonality and recombination in genetically differentiated subgroups of Cryptococcus gattii. Eukaryotic Cell 4: 1403–1409. https://doi.org/10.1128/EC.4.8.1403-1409.2005
Campbell, L.T., Fraser, J.A., Nichols, C.B., Dietricht, F., Carter, D.A. and Heitman, J. (2005) Clinical and environmental isolates of Cryptococcus gattii from Australia that retain sexual fecundity. Eukaryotic Cell 4: 1410–1415. doi: 10.1128/EC.4.8.1410-1419.2005
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Halliday, C.L. and Carter, D.A. (2003) Clonal reproduction and limited dispersal in an environmental population of Cryptococcus neoformans isolates from Australia. Journal of Clinical Microbiology 41:703–711. doi: 10.1128/JCM.41.2.703-711.2003
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Tran-Dinh, N., Pitt, J.I. and Carter, D.A. (1999) Molecular genotype analysis of natural toxigenic and non-toxigenic isolates of Aspergillus flavus and Aspergillus parasiticus. Mycological Research 103: 1485–1490. https://doi.org/10.1017/S0953756299008710
Halliday, C.L., Bui, T., Krockenberger, M., Malik, R., Ellis, D.H. and Carter, D.A. (1999) Presence of alpha and a mating types in environmental and clinical collections of Cryptococcus neoformans var. gattii strains from Australia. Journal of Clinical Microbiology 37: 2920–2926. DOI: 10.1128/JCM.37.9.2920-2926.1999