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Multilocus Sequence Typing Reveals Extensive Genetic Diversity of the Emerging Fungal Pathogen Scedosporium
Azian Harun1,2, Alex Kan1, Katharina Schwabenbauer1
1Molecular Mycology Research Laboratory, Centre for Infectious Diseases and Microbiology, Faculty of Medicine and Health, Sydney Medical School, Westmead Clinical School, Sydney Institute for Infectious Diseases, Westmead Hospital-Research and Education Network, Westmead Institute for Medical Research, University of Sydney, Sydney, NSW, Australia.
Abstract:
Scedosporium spp. are the second most prevalent filamentous fungi after Aspergillus spp. recovered from cystic fibrosis (CF) patients in various regions of the world. Although invasive infection is uncommon prior to lung transplantation, fungal colonization may be a risk factor for invasive disease with attendant high mortality post-transplantation. Abundant in the environment, Scedosporium aurantiacum has emerged as an important fungal pathogen in a range of clinical settings. To investigate the population genetic structure of S. aurantiacum, a MultiLocus Sequence Typing (MLST) scheme was developed, screening 24 genetic loci for polymorphisms on a tester strain set. The six most polymorphic loci were selected to form the S. aurantiacum MLST scheme: actin (ACT), calmodulin (CAL), elongation factor-1α (EF1α), RNA polymerase subunit II (RPB2), manganese superoxide dismutase (SOD2), and β-tubulin (TUB). Among 188 global clinical, veterinary, and environmental strains, 5 to 18 variable sites per locus were revealed, resulting in 8 to 23 alleles per locus. MLST analysis observed a markedly high genetic diversity, reflected by 159 unique sequence types. Network analysis revealed a separation between Australian and non-Australian strains. Phylogenetic analysis showed two major clusters, indicating correlation with geographic origin. Linkage disequilibrium analysis revealed evidence of recombination. There was no clustering according to the source of the strains: clinical, veterinary, or environmental. The high diversity, especially amongst the Australian strains, suggests that S. aurantiacum may have originated within the Australian continent and was subsequently dispersed to other regions, as shown by the close phylogenetic relationships between some of the Australian sequence types and those found in other parts of the world. The MLST data are accessible at http://mlst.mycologylab.org. This is a joined publication of the ISHAM/ECMM working groups on "Scedosporium/Pseudallescheria Infections" and "Fungal Respiratory Infections in Cystic Fibrosis".
Insights
Scedosporium aurantiacum, a fungus found in cystic fibrosis patients, shows high genetic diversity globally. Australian strains are particularly diverse, suggesting this region as a potential origin and highlighting the need for further research into its population structure.
Area of Science:
- Mycology and Population Genetics
- Fungal Pathogenesis and Epidemiology
Background:
- Scedosporium spp. are significant filamentous fungi, second only to Aspergillus spp. in prevalence among cystic fibrosis patients.
- Scedosporium aurantiacum, an environmental fungus, is increasingly recognized as a pathogen, particularly in post-transplantation settings.
- Understanding the genetic diversity of S. aurantiacum is crucial for managing its clinical and environmental impact.
Purpose of the Study:
- To develop and implement a MultiLocus Sequence Typing (MLST) scheme for Scedosporium aurantiacum.
- To investigate the population genetic structure, diversity, and geographic distribution of S. aurantiacum.
- To explore potential origins and dispersal patterns of S. aurantiacum strains.
Main Methods:
- Developed an MLST scheme using six polymorphic loci (ACT, CAL, EF1α, RPB2, SOD2, TUB) from 24 candidate genes.
- Analyzed 188 global strains from clinical, veterinary, and environmental sources using the developed MLST scheme.
- Employed network and phylogenetic analyses to assess genetic relationships and population structure.
Main Results:
- Identified high genetic diversity within S. aurantiacum, with 159 unique sequence types found among 188 strains.
- Observed distinct clustering of Australian strains compared to non-Australian strains, suggesting geographic differentiation.
- Demonstrated evidence of recombination and no correlation between genetic clusters and strain source (clinical, veterinary, environmental).
Conclusions:
- The high genetic diversity, particularly in Australian strains, supports the hypothesis of an Australian origin for S. aurantiacum.
- The study provides a valuable MLST dataset for future epidemiological and population genetic studies of S. aurantiacum.
- Findings contribute to understanding the global dispersal and evolutionary history of this emerging fungal pathogen.
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