Functional Characterization of Clinical Isolates of the Opportunistic Fungal Pathogen Aspergillus nidulans
| Autor: | Gustavo H. Goldman, Ian D. Reid, Verônica Soares Brauer, Jacob L. Steenwyk, Laure Nicolas Annick Ries, Anna Huttenlocher, Clara Valero, Rafael Silva-Rocha, Fausto Almeida, Marina Marcet-Houben, Berl R. Oakley, Nancy P. Keller, Flávio V. Loures, Fernando Rodrigues, Katrien Lagrou, Abigail L. Lind, Adrian Tsang, Erin McDonnell, Lilian Pereira Silva, Agustin Resendiz-Sharpe, Toni Gabaldón, Taylor J. Schoen, Rafael Wesley Bastos, Antonis Rokas, Milton T. Drott |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Adult
Male Molecular Biology and Physiology Neutropenia clinical isolates lcsh:QR1-502 Virulence Context (language use) Granulomatous Disease Chronic Microbiology lcsh:Microbiology Aspergillus nidulans Aspergillus fumigatus 03 medical and health sciences Mice Chronic granulomatous disease Phagocytosis Cell Wall medicine Animals Aspergillosis Humans Molecular Biology Gene Immunodeficiency Zebrafish 030304 developmental biology 0303 health sciences Aspergillus Mice Inbred BALB C biology 030306 microbiology Genomics biology.organism_classification medicine.disease Phenotype metabolomics QR1-502 Carbon 3. Good health Mice Inbred C57BL genome sequencing Female VIRULÊNCIA Research Article |
| Zdroj: | mSphere Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP mSphere, Vol 5, Iss 2, p e00153-20 (2020) mSphere, Vol 5, Iss 2 (2020) |
| Popis: | Immunocompromised patients are susceptible to infections with opportunistic filamentous fungi from the genus Aspergillus. Although A. fumigatus is the main etiological agent of Aspergillus species-related infections, other species, such as A. nidulans, are prevalent in a condition-specific manner. A. nidulans is a predominant infective agent in patients suffering from chronic granulomatous disease (CGD). A. nidulans isolates have mainly been studied in the context of CGD although infection with A. nidulans also occurs in non-CGD patients. This study carried out a detailed biological characterization of two non-CGD A. nidulans clinical isolates and compared the results to those with a reference strain. Phenotypic, metabolomic, and genomic analyses highlight fundamental differences in carbon source utilization, stress responses, and maintenance of cell wall integrity among the strains. One clinical strain had increased virulence in models with impaired neutrophil function. Just as in A. fumigatus, strain heterogeneity exists in A. nidulans clinical strains that can define virulence traits. 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. IMPORTANCE Immunocompromised patients are susceptible to infections with opportunistic filamentous fungi from the genus Aspergillus. Although A. fumigatus is the main etiological agent of Aspergillus species-related infections, other species, such as A. nidulans, are prevalent in a condition-specific manner. A. nidulans is a predominant infective agent in patients suffering from chronic granulomatous disease (CGD). A. nidulans isolates have mainly been studied in the context of CGD although infection with A. nidulans also occurs in non-CGD patients. This study carried out a detailed biological characterization of two non-CGD A. nidulans clinical isolates and compared the results to those with a reference strain. Phenotypic, metabolomic, and genomic analyses highlight fundamental differences in carbon source utilization, stress responses, and maintenance of cell wall integrity among the strains. One clinical strain had increased virulence in models with impaired neutrophil function. Just as in A. fumigatus, strain heterogeneity exists in A. nidulans clinical strains that can define virulence traits. |
| Databáze: | OpenAIRE |
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