ReviewBiological, biochemical and molecular aspects of Scedosporium aurantiacum, a primary and opportunistic fungal pathogen
Introduction
Scedosporium spp. are ubiquitous opportunistic pathogenic fungi that are significant emergent agents of disease increasingly identified partially due to application of new molecular identification technologies to identify and to distinguish between these fungi. The range of infections caused by Scedosporium spp. is broad including the lungs, central nervous system (CNS), bone, joint, skin and subcutaneous tissue (reviewed in Cooley et al., 2007, Cortez et al., 2008, Slavin et al., 2015). Other than causing invasive disease, Scedosporium spp. also colonise the respiratory tract of cystic fibrosis (CF) patients and patients with prior lung damage (Pihet et al., 2009, Blyth et al., 2010a, Blyth et al., 2010b).
Scedosporium spp. are cosmopolitan fungi. Recent large scale studies in CF patients carried out in Germany (Sedlacek et al. 2015) have reported S. apiospermum and S. boydii as the most predominant Scedosporium species in patient samples with an overall prevalence of 3.1 %. In France, the overall prevalence of Scedosporium species in CF patient samples was 4 % but the distribution of the different Scedosporium species was not investigated (Parize et al., 2014). There are also reports on colonisation and infection due to Scedosporium spp. in the setting of CF and in immunocompromised patients in Northern Spain (Lackner et al., 2011). In Australia and in some European countries including France and Austria, these fungi are the second most common filamentous fungi colonising the airways of CF patients (Cimon et al., 2000, Blyth et al., 2010a: Masoud-Landgraf et al., 2014) and overall, account for 33.3 % of invasive fungal disease due to filamentous fungi by other than Aspergillus species (Slavin et al., 2015). Scedosporium infections cause 25–29 % of non-Aspergillus infections in organ transplant recipients in the USA and may occur post-surgery (Husain et al., 2003, Cortez et al., 2008, Pihet et al., 2009). Recently, Scedosporium spp. have also been identified as a causative agent of mycetomas in Brazil (Sampaio et al., 2017), yet Scedosporium infections remain rare in China (Wang et al., 2015). In Australia, Scedosporium spp. are found in urban environment (see also below) and their presence in relatively high frequency is associated with environments of high human activity in Austria and other parts of Europe (Kaltseis et al., 2009, Rougeron et al., 2018).
While particular aspects of Scedosporium spp. have been discussed in previously published papers, this review focuses on bringing together the current knowledge of the biology, biochemistry and molecular characteristics of S. aurantiacum, an opportunistic pathogenic species colonising human lungs.
Section snippets
The genus Scedosporium and the taxonomic position of S. aurantiacum
The genus anamorph Scedosporium with its teleomorph Pseudallescheria has undergone numerous changes with the introduction of molecular phylogenetics, which has led to an increasing resolution at and below the species level. In addition, the fundamental change in fungal taxonomy allowing only a single name per fungal species, effectively abolishing the dual nomenclature based on the anamorph/teleomorph concept (Mcneill et al., 2012) has resulted in the adoption of the name Scedosporium at the
Metabolic profiling of S. aurantiacum
Metabolic profiling defines the metabolic pathways of the organism reflecting the dynamic response of the organism to genetic modification and physiological, pathophysiological, and/or developmental stimuli. It also measures the real outcome of potential changes suggested by genomic and proteomic analyses. Traditional nutrient utilisation assays are performed on a defined minimal medium (solid or liquid) supplemented with the nutrient of choice (e.g. carbon, nitrogen, sulphur, phosphorous and
Scedosporium genomics
Genomes of at least four Scedosporium species have been sequenced including an S. aurantiacum strain WM 09.24 (CBMS136047), isolated from soil, Circular Quay, Sydney, Australia (Harun et al., 2010a), S. apiospermum strain IHEM 14462 isolated from a sputum sample of a CF patient in France (Vandeputte et al., 2014), S. boydii clinical isolate (Duvaux et al., 2017) and another S. apiospermum strain (Morales et al., 2017). Genome sequencing of the highly virulent environmental strain S. aurantiacum
Scedosporium aurantiacum as an infectious agent
The ecological niches of this species, clinical associations and potential for causing invasive fungal disease remain to be more clearly delineated. Scedosporium species are increasingly recognised as colonisers of the lung in CF and in other forms of chronic lung disease (Cooley et al., 2007, Pihet et al., 2009, Liu et al., 2013). Since most epidemiological studies of CF related filamentous fungi have focussed on Aspergillus, the prevalence of Scedosporium species may be underestimated and
Fungal-microbial interactions in CF lung
The most prevalent and clinically important bacterium in a CF lung is Pseudomonas aeruginosa, which is known to cause recurrent pulmonary exacerbations in 80 % of CF patients and eventual lung decline (Harrison, 2007). The study of the mechanisms of bacterial–fungal infections and their consequences hence is of high priority. P. aeruginosa, has been reported to suppress the growth of a number of cystic fibrosis related fungi, such as A. fumigatus, Candida albicans as well as other fungi e.g.
Interaction of Scedosporium spp. with epithelial lung cells
The clinical importance of host response to bacterial–fungal interactions has been highlighted in a number of studies (e.g. Allard et al., 2009, Peleg et al., 2010). Although in vitro testing allows studying the interactions between bacteria and fungi in a controlled environment, their authenticity is hampered by the absence of the host immune response (Peleg et al., 2010). This disadvantage can be overcome to some extent using various cell culture models that involve disease specific mucosal
S. aurantiacum proteases as potential virulence factors
In spite of the increasing importance of S. aurantiacum, very little is known about the virulence factors expressed by this fungal pathogen and the development of preventative strategies is limited. Infections caused by S. boydii highly resemble those of A. fumigatus whose secreted proteases have been shown to function as virulence factors (Birinci et al., 2014). A 33 kDa subtilisin-like protease from the fungal culture supernatant of S. boydii has been purified and characterised (Larcher et al.
Conclusions and future prospects
S. aurantiacum is an emerging human pathogen, which is acquired from the environment, where it occurs widely. Development of high-throughput molecular, proteomic and biochemical technologies have led to a revised taxonomy of the genus Scedosporium, and allowed the positioning and better understanding of S. aurantiacum as a primary pathogen within this genus. Automated analysis methods and the generation of annotated genomes will assist in further mapping of the metabolic pathways of S.
Conflict of interest
None declared.
References (97)
- et al.
Characterisation of the A549 cell line as a type II pulmonary epithelial cell model for drug metabolism
Exp. Cell Res.
(1998) - et al.
Molecular diagnostic methods for invasive fungal disease: the horizon draws nearer
Pathology
(2015) - et al.
Population-based surveillance for scedosporiosis in Australia: epidemiology, disease manifestations and emergence of Scedosporium aurantiacum infection
Clin. Microbiol. Infect.
(2009) - et al.
What is the clinical significance of filamentous fungi positive sputum cultures in patients with cystic fibrosis?
J. Cyst. Fibros.
(2013) - et al.
Scedosporium aurantiacum brain abscess after near-drowning in a survivor of a tsunami in Japan
Resp. Inv.
(2013) - et al.
Impact of Scedosporium apiospermum complex seroprevalence in patients with cystic fibrosis
J. Cyst. Fibros.
(2014) - et al.
Involvement of peptidorhamnomannan in the interaction of Pseudallescheria boydii and HEp2 cells
Microb. Infect.
(2004) - et al.
Prevalence of Scedosporium species and Lomentospora prolificans in patients with cystic fibrosis in a multicenter trial by use of a selective medium
J. Cyst. Fibros.
(2015) - et al.
Matrix-assisted laser desorption ionization-time of flight mass spectrometry for fast and accurate identification of Pseudallescheria/Scedosporium species
Clin. Microbiol. Infect.
(2014) - et al.
Th2 allergic immune response to inhaled fungal antigens is modulated by TLR-4-independent bacterial products
Eur. J. Immunol.
(2009)