Ca37 antigorputz monoklonalaren efektua Candida generoko espezieetan

Abstract

[EU] Candida generoa infekzio nosokomialen onddo-eragile nagusiena da, batez ere Candida albicans espeziea. Hala ere, azken urteotan Candida parapsilosis, Candida glabrata eta Candida auris espezieen intzidentziak handitu dira, antifungikoekiko erakusten duten erresistentzia handiarekin erlazionatuta. Gaur egun eskuragarri dauden antifungikoak, gutxi izateaz gain, garestiak eta toxikoak dira gizakiontzat eta haiekiko erresistentzia handituko dela dirudi, bere erabilera handiaren ondorioz. Medikamentu berrien premia handiari aurre egiteko antigorputz monoklonalak asko aztertu dira, haien eraginkortasuna frogatu delarik. Hori dela eta, C. albicansen zelula-paretako Adh1 proteinarekiko espezifikoa zen Ca37 antigorputz monoklonala sortu zen. Antigorputzak espezie horretan emaitza positiboak azaldu ditu in vitro eta in vivo, hazkuntza zein birulentzia murriztuz. Candida generoko espezieen Adh proteinaren homologia altua kontuan hartuta, Ca37 antigorputzak C. parapsilosis eta C. glabrata onddoetan duen efektua ikertu zen, C. aurisen pasadan urtean burututako Gradu Amaierako Lanean frogatu zelarik. Western Blotean antigorputzak C. parapsilosis eta C. glabrata zelula-paretako proteinen artean 3 eta 4 puntu ezagutu zituen, hurrenez hurren, espezie horien Adh proteinaren pisu molekular eta puntu isoelektriko teorikoen antzekoak direnak. Gainera, antigorputzak in vitro C. parapsilosisen % 42ko hazkuntza-inhibizioa eragin zuen. Antigorputzak efektu opsonizatzailea ote zuen ezezaguna zenez espezie guztietan, aipaturiko lau Candida espezieak RAW 264.7 makrofagoekin ko-inkubatu ziren. Antigorputzak makrofagoen fagozitosia indartu zuen, espezie guztien fagozitosi ehunekoa handituz eta C. auris eta C. parapsilosisen indize fagozitikoa handituz, batez ere lehenengo orduan. Bestalde, in vivo erabilitako Galleria mellonella animalia-ereduan, antigorputzak C. parapsilosis eta C. glabrata onddoekin infektatutako larben biziraupena luzatu dezakeela dirudi, lortutako emaitzak estatistikoki adierazgarriak ez izan arren. Hortaz, nahiz eta esperimentu batzuk errepikatu behar diren, lortutako emaitzek Ca37 antigorputz monoklonalak etorkizunean C. parapsilosis eta C. glabratak eragindako infekzioen aurka aplikazio terapeutikoa izan dezakeela aditzera ematen dute. Azkenik, C. albicans eta C. aurisen lortutako emaitza berriek, espezie horiekiko antigorputzaren eraginkortasunaren ebidentzia indartzen dute.

[EN] Candida genus is the principal fungus of nosocomial infections, especially the species Candida albicans. In recent years, however, the incidence of the species Candida parapsilosis, Candida glabrata and Candida auris has increased, in relation to their great resistance to antifungals. The antifungals available today, in addition to being few, are expensive and toxic to humans and it seems that resistance to them will continue increasing due to their high use. To address the high need for new drugs against fungus, many monoclonal antibodies have been widely studied and they have been shown to be effective. Ca37 monoclonal antibody is specific to the Adh1 protein in the cell wall of C. albicans. The antibody has shown positive results in this species in vitro and in vivo, reducing growth and virulence. Considering the high homology of the Adh protein of species of the genus Candida, the effect of the Ca37 antibody on C. parapsilosis and C. glabrata was studied. C. auris was studied in last year´s Undergraduate Thesis Project. In the Western Blot the antibody recognized 3 and 4 points between the proteins of the cell wall of C. parapsilosis and C. glabrata, respectively, similar to the molecular weights and isoelectric points of the Adh protein of these species. In addition, the antibody produced 42% growth inhibition in vitro in C. parapsilosis. As it was unknown whether the antibody had an opsonizing effect on all species, the four Candida species mentioned were co-incubated with the macrophages RAW 264.7. The antibody strengthened the phagocytosis of macrophages, increasing the percentage of phagocytosis in all species, and increasing the phagocytic index in C. auris and C. parapsilosis, especially at the first hour. On the other hand, in the animal model Galleria mellonella used in vivo, the antibody appears to prolong the survival of larvae infected with C. parapsilosis and C. glabrata, although the results obtained are not statistically significant. Therefore, although some experiments must be repeated, the results obtained suggest that monoclonal Ca37 antibody may have therapeutic application against C. parapsilosis and C. glabrata infections in the future. Lastly, the new results obtained in C. albicans and C. auris reinforce the evidence of the effectiveness of the antibody to these species.