Fungicidal Monoclonal Antibody C7 Interferes with Iron Acquisition in Candida albicans

We have developed a monoclonal antibody (MAb), C7, that reacts with the Als3p and enolase present in the Candida albicans cell wall and exerts three anti-Candida activities: candidacidal activity and inhibition of both adhesion and filamentation. To investigate the mode of action of MAb C7 on fungal viability, we examined changes in the genome-wide gene expression profile of C. albicans grown in the presence of a subinhibitory concentration of MAb C7 (12.5 μg/ml) by using microarrays. A total of 49 genes were found to be differentially expressed upon treatment with MAb C7. Of these, 28 were found to be upregulated and 21 were found to be downregulated. The categories of upregulated genes with the largest number of variations were those involved in iron uptake or related to iron homeostasis (42.86%), while the energy-related group accounted for 38.10% of the downregulated genes (8/21). Results were validated by real-time PCR. Since these effects resembled those found under iron-limited conditions, the activity of MAb C7 on C. albicans mutants with deletions in key genes implicated in the three iron acquisition systems described in this yeast was also assessed. Only mutants lacking the TPK1 gene and, to a lesser extent, the TPK2 gene were less sensitive to the candidacidal effect of MAb C7. FeCl3 or hemin at concentrations of ≥7.8 μM reversed the candidacidal effect of MAb C7 on C. albicans in a concentration-dependent manner. The results presented in this study provide evidence that the candidacidal effect of MAb C7 is related to the blockage of the reductive iron uptake pathway of C. albicans.
This project has been financed with grants IT-264-07 from the Department of Education, Universities and Research, Basque Government (to J.P. and M.D.M.), GEN2006-27775-C2-E/PAT (to A.D.), and SA 141A08 from Junta de Castilla y León (to A.D.), Spain. Sonia Brena was supported by a University of the Basque Country (Ayudas para la Formación de Personal Investigador) grant, and Jonathan Cabezas-Olcoz was supported by a Spanish Ministry of Education grant (Programa de Formación del Profesorado Universitario AP2006- 02929).