Background: MUC7 12-mer is a derivative of the human salivary mucin MUC7. While this cationic antimicrobial peptide possesses potent activity against Candida albicans, its mechanism of action remains poorly understood. We examined changes in the gene expression profile of C. albicans upon exposure to the MUC7 12-mer in order to gain insight into the mechanism of action of (and resistance to) this peptide. Methods: C. albicans DSI (a clinical strain) was grown to an OD600 of ~0.1, and then exposed to the MUC7 12-mer (6 μM) until an OD600 of 0.4 was reached. RNA was isolated for DNA microarray analysis. Gene expression profiles were compared between treated and untreated cells. Experiments were performed in duplicate. Differential expression of selected genes was verified by real-time RT-PCR. Results: A total of 531 genes were up-regulated and 468 genes were down-regulated in response to treatment with the MUC7 12-mer. Up-regulated genes included genes regulated by the calcineurin/Crz1 pathway, including ECM331, IFO2, IML2, SFK1, SAT4, SEC72, MNT43, MNN41, PGA23, PDI1, PLC3, RNH1, RTA4, SAC6, VPS1, and CRZ1 itself. Other up-regulated genes included those encoding subunits of the 20S and 26S proteasome (PRE10, PRE5, PRE6, YTA7, RTT2, RPT4, RPN5, RPN6, RPN9). Other differentially expressed genes included those involved in cell stress, cell wall maintenance, iron metabolism, and small molecule transport. Conclusions: These data suggest that in C. albicans, the MUC7 12-mer activates the calcineurin pathway and the 20S and 26S proteasome. This peptide also appears to impact both cell wall and iron metabolism in this pathogen. Further study of the specific role of these transcriptional activation programs in the activity of (and resistance to) the MUC7 12-mer is warranted.
Full conference title:
46th Interscience Conference on Antimicrobial Agents and Chemotherapy
- ICAAC 46th