Functional Characterization of Clinical Isolates of the Opportunistic Fungal Pathogen Aspergillus nidulans
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Issue Date
2020-04-08Author
Bastos, Rafael Wesley
Valero, Clara
Silva, Lilian Pereira
Schoen, Taylor
Drott, Milton
Brauer, Verônica
Silva-Rocha, Rafael
Lind, Abigail
Steenwyk, Jacob L.
Rokas, Antonis
Rodrigues, Fernando
Resendiz-Sharpe, Agustin
Lagrou, Katrien
Marcet-Houben, Marina
Gabaldón, Toni
McDonnell, Erin
Reid, Ian
Tsang, Adrian
Oakley, Berl R.
Loures, Flávio Vieira
Almeida, Fausto
Huttenlocher, Anna
Keller, Nancy P.
Ries, Laure Nicolas Annick
Goldman, Gustavo H.
Publisher
American Society for Microbiology
Type
Article
Article Version
Scholarly/refereed, publisher version
Rights
© 2020 Bastos et al.
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Show full item recordAbstract
Aspergillus nidulans is an opportunistic fungal pathogen in patients with immunodeficiency, and virulence of A. nidulans isolates has mainly been studied in the context of chronic granulomatous disease (CGD), with characterization of clinical isolates obtained from non-CGD patients remaining elusive. This study therefore carried out a detailed biological characterization of two A. nidulans clinical isolates (CIs), obtained from a patient with breast carcinoma and pneumonia and from a patient with cystic fibrosis that underwent lung transplantation, and compared them to the reference, nonclinical FGSC A4 strain. Both CIs presented increased growth in comparison to that of the reference strain in the presence of physiologically relevant carbon sources. Metabolomic analyses showed that the three strains are metabolically very different from each other in these carbon sources. Furthermore, the CIs were highly susceptible to cell wall-perturbing agents but not to other physiologically relevant stresses. Genome analyses identified several frameshift variants in genes encoding cell wall integrity (CWI) signaling components. Significant differences in CWI signaling were confirmed by Western blotting among the three strains. In vivo virulence studies using several different models revealed that strain MO80069 had significantly higher virulence in hosts with impaired neutrophil function than the other strains. In summary, this study presents detailed biological characterization of two A. nidulans sensu stricto clinical isolates. Just as in Aspergillus fumigatus, strain heterogeneity exists in A. nidulans clinical strains that can define virulence traits. Further studies are required to fully characterize A. nidulans strain-specific virulence traits and pathogenicity.
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This work is licensed under a Creative Commons Attribution 4.0 International License.
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Citation
Bastos, R. W., Valero, C., Silva, L. P., Schoen, T., Drott, M., Brauer, V., Silva-Rocha, R., Lind, A., Steenwyk, J. L., Rokas, A., Rodrigues, F., Resendiz-Sharpe, A., Lagrou, K., Marcet-Houben, M., Gabaldón, T., McDonnell, E., Reid, I., Tsang, A., Oakley, B. R., Loures, F. V., … Goldman, G. H. (2020). Functional Characterization of Clinical Isolates of the Opportunistic Fungal Pathogen Aspergillus nidulans. mSphere, 5(2), e00153-20. https://doi.org/10.1128/mSphere.00153-20
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