Review
Biological, biochemical and molecular aspects of Scedosporium aurantiacum, a primary and opportunistic fungal pathogen

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Abstract

The present review summarises the current knowledge of the biology, biochemistry and molecular aspects of S. aurantiacum in context with the broader knowledge on Scedosporium spp, generated over the past decade. Recently, the genus has undergone two taxonomical reviews. S. aurantiacum is widely distributed in all ecological niches and geographical locations. It is a highly pathogenic opportunist capable of causing a broad range of diseases via infections occurring in the lungs, sinuses, eyes, bones, central nervous system and internal organs. While S. aurantiacum has a minor role in the colonisation of lungs in Germany and France, in Australia, it comprises approximately one-third of Scedosporium spp. recovered from cystic fibrosis lungs where it may co-exist with other prokaryotic lung inhabitants such as Pseudomonas aeruginosa. However, very little is known about mixed bacterial–fungal interactions or host–fungal interactions in the lungs, all of which may have an impact on disease outcome. Also, the nature of potential virulence factors such as production of particular proteases would require more research. A wide range of molecular diagnostic techniques now available can facilitate rapid and accurate identification of Scedosporium spp. in clinical specimens and environmental samples. However, molecular tools allowing gene overexpression and knockout studies are yet to be fully developed. A draft genome is currently available for S. aurantiacum strain WM 09.24 (CBS136047), an Australian environmental isolate. The emerging genomic tools and metabolic and transcriptomic studies discussed will further advance understanding of the pathogenic mechanisms of members of the genus Scedosporium, including S. aurantiacum.

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)

  • M. Arvanitis et al.

    Molecular and non molecular diagnostic methods for invasive fungal infections

    Clin. Microbiol. Rev.

    (2014)
  • H.M. Bandara et al.

    Pseudomonas aeruginosa inhibits in-vitro Candida biofilm development

    BMC Microbiol.

    (2010)
  • A. Birinci et al.

    Investigation of acid proteinase and phospholipase activity as virulence factors in clinical Aspergillus spp. isolates

    Mikrobiyol. Bul.

    (2014)
  • C.C. Blyth et al.

    Detection of occult Scedosporium species in respiratory tract specimens from patients with cystic fibrosis by use of selective media

    J. Clin. Microbiol.

    (2010)
  • C.C. Blyth et al.

    Clinical associations and prevalence of Scedosporium spp. in Australian cystic fibrosis patients: identification of novel risk factors?

    Med. Mycol.

    (2010)
  • B.R. Bochner et al.

    Phenotype microarrays for high-throughput phenotypic testing and assay of gene function

    Genome Res.

    (2001)
  • B.R. Bochner

    New technologies to assess genotype-phenotype relationships

    Nat. Rev. Genet.

    (2003)
  • J.P. Bouchara et al.

    Development of an oligonucleotide array for direct detection of fungi in sputum samples from patients with cystic fibrosis

    J. Clin. Microbiol.

    (2009)
  • C. Cassagne et al.

    Performance of MALDI TOF MS platforms for fungal identification

    Mycoses

    (2016)
  • S. Carpenter et al.

    How important are Toll-like receptors for antimicrobial responses?

    Cell Microbiol.

    (2007)
  • M.V. Castelli et al.

    Development and validation of a quantitative PCR assay for diagnosis of scedosporiosis

    J. Clin. Microbiol.

    (2008)
  • M.V. Castelli et al.

    Novel antifungal agents: a patent review (2013–present

    Exp. Opin. Ther. Pat.

    (2017)
  • S.C. Chen et al.

    Challenges in laboratory detection of fungal pathogens in the airways of cystic fibrosis patients

    Mycopathologia

    (2018)
  • S.C.A. Chen et al.

    Pseudomonas aeruginosa Inhibits the Growth of Scedosporium and Lomentospora In Vitro

    Mycopathologia

    (2018)
  • B. Cimon et al.

    Clinical significance of Scedosporium apiospermum in patients with cystic fibrosis

    Eur. J. Clin. Microbiol. Infect. Dis.

    (2000)
  • L. Cooley et al.

    Infection with Scedosporium apiospermum and S. prolificans, Australia

    Emerg. Infect. Dis.

    (2007)
  • K.J. Cortez et al.

    Infections caused by Scedosporium spp

    Clin. Microbiol. Rev.

    (2008)
  • P.W. Crous et al.

    Fungal Planet description sheets: 469–557

    Persoonia

    (2016)
  • C. Cugini et al.

    Candida albicans-produced farnesol stimulates Pseudomonas quinolone signal production in LasR-defective Pseudomonas aeruginosa strains

    Microbiology

    (2010)
  • B.A. da Silva et al.

    Extracellular peptidase in the fungal pathogen Pseudallescheria boydii

    Curr. Microbiol.

    (2006)
  • B.L. Duell et al.

    Epithelial cell co-culture models for studying infectious diseases: benefits and limitations

    J. Biomed. Biotechnol.

    (2011)
  • L. Duvaux et al.

    Draft genome sequence of Scedosporium boydii

    Genome Announc.

    (2017)
  • J.A. Ferreira et al.

    Inhibition of Aspergillus fumigatus and its biofilm by Pseudomonas aeruginosa is dependent on the source, phenotype and growth conditions of the bacterium

    Mol. Cell. Proteomics

    (2012)
  • G.M. Gersuk et al.

    Dectin-1 and TLRs permit macrophages to distinguish between different Aspergillus fumigatus cellular states

    J. Immunol.

    (2006)
  • F. Gilgado et al.

    Molecular phylogeny of the Pseudallescheria boydii species complex: proposal of two new species

    J. Clin. Microbiol.

    (2005)
  • F. Gilgado et al.

    Molecular and phenotypic data supporting distinct species statuses for Scedosporium apiospermum and Pseudallescheria boydii and the proposed new species Scedosporium dehoogii

    J. Clin. Microbiol.

    (2008)
  • F. Gilgado et al.

    Different virulence of the species of the Pseudallescheria boydii complex

    Med. Mycol.

    (2009)
  • J. Guarro et al.

    Scedosporium apiospermum: changing clinical spectrum of a therapy-refractory opportunist

    Med. Mycol.

    (2006)
  • J. Guinea et al.

    In vitro antifungal activities of isavuconazole (BAL4815), voriconazole, and fluconazole against 1007 isolates of zygomycete, Candida, Aspergillus, Fusarium, and Scedosporium species

    Antimicrob. Agents Chemother.

    (2008)
  • Z. Han

    Proteases of Scedosporium aurantiacum, an Opportunistic Fungal Pathogen

    (2017)
  • Z. Han et al.

    Secretion of proteases by an opportunistic fungal pathogen Scedosporium aurantiacum

    PLoS One

    (2017)
  • A. Harun et al.

    Genotyping of Scedosporium species: a review of molecular approaches

    Med. Mycol.

    (2009)
  • A. Harun et al.

    Abundance of Pseudallescheria/Scedosporium species in the Australian urban environment suggests a possible source for scedosporiosis including the colonization of airways in cystic fibrosis

    Med. Mycol.

    (2010)
  • A. Harun et al.

    Scedosporium aurantiacum is as virulent as S. prolificans, and shows strain-specific virulence differences, in a mouse model

    Med. Mycol.

    (2010)
  • A. Harun et al.

    Development and validation of a multiplex PCR for detection of Scedosporium spp. in respiratory tract specimens from patients with cystic fibrosis

    J. Clin. Microbiol.

    (2011)
  • D.L. Hawksworth et al.

    The Amsterdam declaration on fungal nomenclature

    IMA Fungus

    (2011)
  • F. Harrison

    Microbial ecology of the cystic fibrosis lung

    Microbiology

    (2007)
  • A. Hector et al.

    Update on host-pathogen interactions in cystic fibrosis lung disease

    Mol. Cell. Pediatr.

    (2016)
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