Study of Humoral Responses against Lomentospora/Scedosporium spp. and Aspergillus fumigatus to Identify L. prolificans Antigens of Interest for Diagnosis and Treatment

Abstract

The high mortality rates of Lomentospora prolificans infections are due, above all, to the tendency of the fungus to infect weakened hosts, late diagnosis and a lack of effective therapeutic treatments. To identify proteins of significance for diagnosis, therapy or prophylaxis, immunoproteomics-based studies are especially important. Consequently, in this study murine disseminated infections were carried out using L. prolificans, Scedosporium aurantiacum, Scedosporium boydii and Aspergillus fumigatus, and their sera used to identify the most immunoreactive proteins of L. prolificans total extract and secreted proteins. The results showed that L. prolificans was the most virulent species and its infections were characterized by a high fungal load in several organs, including the brain. The proteomics study showed a high cross-reactivity between Scedosporium/Lomentospora species, but not with A. fumigatus. Among the antigens identified were, proteasomal ubiquitin receptor, carboxypeptidase, Vps28, HAD-like hydrolase, GH16, cerato-platanin and a protein of unknown function that showed no or low homology with humans. Finally, Hsp70 deserves a special mention as it was the main antigen recognized by Scedosporium/Lomentospora species in both secretome and total extract. In conclusion, this study identifies antigens of L. prolificans that can be considered as potential candidates for use in diagnosis and as therapeutic targets and the production of vaccines.

ELISA Test for the Serological Detection of Scedosporium/Lomentospora in Cystic Fibrosis Patients

“…The advantage of these kinds of extract is that they involve every interesting antigen. On the contrary, one of their main handicaps is their cross-reactivity against panfungal antigens of closely related fungi (Buldain et al, 2019). In this sense, biochemical studies try to characterize specific proteins for diagnostic purposes, but as little is known about the physiology and biochemistry of Scedosporium, and the number of studies performed in the field is small, only a few proteins of interest have been characterized.…”

“…Extraction of S. boydii secretome was carried out following the methodology described in Buldain et al, 2019, with slight modifications. Briefly, 10 6 conidia/ml were inoculated into PDB and grown for 24 h at 37ºC and 120 rpm.…”

The Host Immune Response to Scedosporium/Lomentospora

“…More recently, Buldain et al (2019) have demonstrated that sera from mice infected intravenously with L. prolificans , S. apiospermum and S. aurantiacum species, but not with A. fumigatus , showed a high cross-reactivity, which is most likely due to the phylogenetic proximity of Scedosporium / Lomentospora species [ 112 ]. This high cross-reactivity makes it impossible to find species-specific antigens inside Scedosporium / Lomentospora , but it may be very useful for differentiating this complex from Aspergillus .…”

“…In the studies of humoral response carried out so far, a large number of targets of Scedosporium / Lomentospora with potential medical applicability have been identified, among which Hsp70, carbohydrate portion of PRM and catalase are of particular interest [ 50 , 51 , 107 , 108 , 109 , 111 , 112 , 115 ]. Nonetheless, so far only catalase A1 from S. boydii has been tested for clinical usefulness [ 111 ].…”

Omics and Bioinformatics Approaches to Identify Novel Antigens for Vaccine Investigation and Development

“…Fungal infections are emerging worldwide, but the number of therapeutic options is restricted and there is a steadily increasing number of fungal clinical isolates resistant to multiple drugs [ 11 ]. Although the fungal pathogens best known belong to the Candida genus, Lomentospora prolificans is an emerging fungal pathogen with the remarkable ability to enter the blood stream and cause disseminated infections [ 12 ]. The situation is of particular concern in severe immunosuppressed patients, particularly in those suffering hematological malignancies [ 12 ].…”