RESUMO
The delay in making a correct diagnosis of Candida auris causes concern in the healthcare system setting, and immunoproteomics studies are important to identify immunoreactive proteins for new diagnostic strategies. In this study, immunocompetent murine systemic infections caused by non-aggregative and aggregative phenotypes of C. auris and by Candida albicans and Candida haemulonii were carried out, and the obtained sera were used to study their immunoreactivity against C. auris proteins. The results showed higher virulence, in terms of infection signs, weight loss, and histopathological damage, of the non-aggregative isolate. Moreover, C. auris was less virulent than C. albicans but more than C. haemulonii. Regarding the immunoproteomics study, 13 spots recognized by sera from mice infected with both C. auris phenotypes and analyzed by mass spectrometry corresponded to enolase, phosphoglycerate kinase, glyceraldehyde-3-phosphate dehydrogenase, and phosphoglycerate mutase. These four proteins were also recognized by sera obtained from human patients with disseminated C. auris infection but not by sera obtained from mice infected with C. albicans or Aspergillus fumigatus. Spot identification data are available via ProteomeXchange with the identifier PXD049077. In conclusion, this study showed that the identified proteins could be potential candidates to be studied as new diagnostic or even therapeutic targets for C. auris.
Assuntos
Candida , Candidíase , Imunoglobulina G , Animais , Camundongos , Candida/imunologia , Candida/patogenicidade , Humanos , Candidíase/imunologia , Candidíase/microbiologia , Candidíase/sangue , Imunoglobulina G/sangue , Antígenos de Fungos/imunologia , Antígenos de Fungos/sangue , Proteômica/métodos , Candida albicans/imunologia , Candida albicans/patogenicidade , Proteínas Fúngicas/imunologia , Fosfoglicerato Mutase/imunologia , Fosfoglicerato Quinase/imunologia , Gliceraldeído-3-Fosfato Desidrogenases/imunologia , Gliceraldeído-3-Fosfato Desidrogenases/metabolismo , Anticorpos Antifúngicos/sangue , Anticorpos Antifúngicos/imunologia , Feminino , VirulênciaRESUMO
The liver, and more specifically, the liver sinusoidal endothelial cells, constitute the beginning of one of the most important responses for the elimination of hematogenously disseminated Candida albicans. Therefore, we aimed to study the mechanisms involved in the interaction between these cells and C. albicans. Transcriptomics-based analysis showed an increase in the expression of genes related to the immune response (including receptors, cytokines, and adhesion molecules), as well as to aerobic glycolysis. Further in vitro analyses showed that IL-6 production in response to C. albicans is controlled by MyD88- and SYK-pathways, suggesting an involvement of Toll-like and C-type lectin receptors and the subsequent activation of the MAP-kinases and c-Fos/AP-1 transcription factor. In addition, liver sinusoidal endothelial cells undergo metabolic reprogramming towards aerobic glycolysis induced by C. albicans, as confirmed by the increased Extracellular Acidification Rate and the overexpression of enolase (Eno2), hexonikase (Hk2) and glucose transporter 1 (Slc2a1). In conclusion, these results indicate that the hepatic endothelium responds to C. albicans by increasing aerobic glycolysis and promoting an inflammatory environment.