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Front. Microbiol. | doi: 10.3389/fmicb.2019.01970

Revealing the virulence potential of clinical and environmental Aspergillus fumigatus isolates using whole-genome sequencing

 Fabiola Puértolas Balint1,  John W. Rossen1, Claudy Oliveira dos Santos1, Monika M. Chlebowicz1, Erwin Raangs1,  Maarten L. van Putten1,  Pedro J. Sola Campoy2,  Li Han3,  Martina Schmidt4, 5 and  Silvia García Cobos1*
  • 1Department of Medical Microbiology and Infection Prevention, University of Groningen, Netherlands
  • 2Reference and Research Laboratory on Antimicrobial Resistance and Healthcare Infections, National Microbiology Centre, Carlos III Health Institute, Spain
  • 3Academy of Military Medical Sciences, Chinese Center For Disease Control and Prevention, China
  • 4Department of Molecular Pharmacology, University of Groningen, Netherlands
  • 5GRIAC research institute, University Medical Center Groningen, Netherlands

Aspergillus fumigatus is considered a common causative agent of human fungal infections. A restricted number of virulence factors have been described, and none of them lead to a differentiation in the virulence level among different strains. Variations in the virulence phenotype depending on the isolate origin, measured as survival percentage in animal infection models, have been previously reported. In this study, we analysed the whole-genome sequence of A. fumigatus isolates from clinical and environmental origins to determine their virulence genetic content. The sample included four isolates sequenced at the University Medical Center Groningen (UMCG), three clinical (two of them isolated from the same patient) and the experimental strain B5233, and the draft genomes of one reference strain, two environmental and two clinical isolates obtained from a public database. The fungal genomes were screened for the presence of virulence-related genes (VRGs) using an in-house database of 244 genes related to thermotolerance, resistance to immune responses, cell wall formation, nutrient uptake, signalling and regulation, and production of toxins/secondary metabolites and allergens. In addition, we performed a variant calling analysis to compare the isolates sequenced at the UMCG and investigated their genetic relatedness using the TRESP (Tandem Repeats located within Exons of Surface Protein coding genes) genotyping method. We neither observed a difference in the virulence genetic content between the clinical isolates causing an invasive infection and a colonising clinical isolate nor between isolates from the clinical and environmental origin. The four novel A. fumigatus sequences had a different TRESP genotype and a total number of genetic variants ranging from 48,590 to 68,352. In addition, a comparative genomics analysis showed the presence of single nucleotide polymorphisms in VRGs and repetitive genetic elements located next to VRG groups, which could influence the regulation of these genes. In conclusion, our genomic analysis revealed a high genetic diversity between environmental and clinical A. fumigatus isolates, as well as between clinical isolates from the same patient, indicating an infection with a mixed-population in the latter case. However, all isolates had a similar virulence genetic content, demonstrating their pathogenic potential at least at the genomic level.

Keywords: Aspergillus fumigatus, Virulence, Whole-genome sequence analysis, clinical and environmental strain, Gene database

Received: 19 Apr 2019; Accepted: 12 Aug 2019.

Copyright: © 2019 Puértolas Balint, Rossen, Oliveira dos Santos, Chlebowicz, Raangs, van Putten, Sola Campoy, Han, Schmidt and García Cobos. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mx. Silvia García Cobos, University of Groningen, Department of Medical Microbiology and Infection Prevention, Groningen, Netherlands,