Mutational analysis of metacaspase CaMca1 and decapping activator Edc3 in the pathogenicity of Candida albicans.
Candida albicans, an opportunistic fungal pathogen, displays apoptotic cell death in response to various stresses and a wide range of antifungal treatments. CaMca1, which is the only metacaspase in C. albicans, has been described as a key player in apoptotic cell death. Edc3 is an mRNA decapping activator and a scaffold protein of processing bodies. Edc3 was previously shown to regulate CaMCA1 expression and oxidative stress-induced apoptosis. In this study, we analyzed the contribution of the catalytic residues of the CaMca1 to the oxidative stress-induced apoptosis and pathogenicity of C. albicans. The CaMCA1C292Amutation decreased caspase activity to a level similar to that observed in the Camca1/Camca1 deletion strain and over-expression of CaMCA1C292Afailed to suppress the oxidative-stress phenotypes of the edc3/edc3 mutant strain. The edc3/edc3, Camca1/Camca1, and CaMCA1C292Amutant strains were not virulent in a murine candidiasis model. Filamentation defects were observed in the Camca1/Camca1 mutant cells, whereas this defect was only partial in CaMCA1C292Amutant cells. These results suggest that CaMca1 and Edc3 play essential roles in the oxidative stress-induced apoptosis and virulence of C. albicans, and also support the notion that Edc3 is a key regulator of CaMca1 expression.
Department of Microbiology and Molecular Biology, College of Bioscience and Biotechnology, Chungnam National University, Daejeon 305-764, Republic of Korea.
Jeong-Hoon
JH
Jeong
Department of Microbiology and Molecular Biology, College of Bioscience and Biotechnology, Chungnam National University, Daejeon 305-764, Republic of Korea.
Seok-Eui
SE
Lee
Department of Microbiology and Molecular Biology, College of Bioscience and Biotechnology, Chungnam National University, Daejeon 305-764, Republic of Korea. Electronic address: jmkim@cnu.ac.kr.
Jinmi
J
Kim
D017209:Apoptosis / Q000235:genetics; D002176:Candida albicans / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D002177:Candidiasis / Q000235:genetics / Q000382:microbiology; D020169:Caspases / Q000096:biosynthesis* / Q000235:genetics; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D025301:Hyphae / Q000235:genetics / Q000254:growth & development; D009154:Mutation; D018384:Oxidative Stress / Q000235:genetics*; D010641:Phenotype; D017382:Reactive Oxygen Species / Q000378:metabolism; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics* / Q000378:metabolism
C000594134:EDC3 protein, Candida albicans; D005656:Fungal Proteins; D017382:Reactive Oxygen Species; D017411:Ribonucleoproteins, Small Nuclear; D020169:Caspases
Apoptosis; CaMCA1(C292A) mutation; CaMca1; Candida albicans; Edc3; Oxidative stress; Pathogenicity