Objectives:
Lomentospora prolificans is an emerging pathogen that causes infections with high mortality rates associated with the lack of effective treatments and the difficulties to perform a rapid and accurate diagnosis. Therefore, it is necessary to deep into the understanding of its pathobiology and the identification of new specific diagnostic markers.
According to this, two main objectives were proposed. A comparative study of pathogenicity between Lomentospora, and the other clinically important filamentous fungus Scedoporium apiospermum, S. aurantiacum and Aspergillus fumigatus was carried out in a murine model. On the other hand, the cross-reactivity with L. prolificans of the serum IgGs from mice infected with the other fungal species was studied, identifying the most immunoreactive antigens. 
Methods:
Swiss female 8-week-old immunocompetent mice were used. They were separated in 5 groups (6 animals/group, except for the group infected with L. prolificans (12 mice)) and infected intravenously with 105 conidia/animal of different fungi (L. prolificans, S. apiospermum, S. aurantiacum and A. fumigatus), and saline solution for the control group. 
Once infected, a daily follow-up of clinical signs associated with infection was carried out. Twenty-eight days after infection, surviving animals were sacrificed for blood and organ extraction. Blood samples were used for obtaining sera and organs for CFU counting and histopathological analyses. Pooled sera from each infected group were used over L. prolificans proteome to detect antigens by 2-DE immunoblotting. Afterwards, the most immunoreactive antigens were identified by LC-MS/MS. 
Results:
Mice infected with Lomenstospora and Scedosporium species developed signs associated with infection, such as changes in fur consistency, weight loss, and neurological signs. In contrast, no signs were observed in A. fumigatus infected mice. 
Survival rates obtained were different, observing 50% in L. prolificans infected group, 83.3% in S. apiospermum and S. aurantiacum, and 100% in A. fumigatus. According to this, in Lomentospora and Scedosporium infected groups high CFU counting were obtained in spleen, kidneys and liver. It is worth highlighting the high number of CFUs observed in the brains of L. prolificans group. Moreover, the histological analysis showed renal affectation of the groups infected with Lomentospora/Scedosporium, being especially relevant the high amount of conidia observed in the case of Lomentospora. However, in animals infected with A. fumigatus, very few CFUs were collected. 
Regarding the immunoproteomics study, the Heat shock protein 70 (Hsp70) was identified as the major antigen, with a percentaje of volume 20 times higher than the next most immunoreactive antigen. All the most immunoreactive antigens showed cross-reactivity with the sera from mice infected with Scedosporium species but not with Aspergillus, which showed a completely different immunome pattern. 
Conclusion:
A model of disseminated infection was developed in immunocompetent mice with Lomentospora and Scedosporium species. Using this model, Lomentospora was shown to be more virulent than Scedoposporium and, above all, Aspergillus species. Moreover, the immunoproteomic study revealed great differences between the antigenic pattern of Lomentospora/Scedosporium and A. fumigatus, which is valuable to identify new diagnostic markers. In this sense, the Hsp70, as the major antigen of Lomentospora/Scedosporium species, stands out as interesting candidate. 




Comparative study of the pathogenicity and humoral response of Lomentospora, Scedosporium and Aspergillus infections in a murine model