Influence of iron regulation on the metabolome of Cryptococcus neoformans.
Iron is an essential nutrient for virtually all organisms and acts as a cofactor for many key enzymes of major metabolic pathways. Furthermore, iron plays a critical role in pathogen-host interactions. In this study, we analyzed metabolomic changes associated with iron availability and the iron regulatory protein Cir1 in a human fungal pathogen Cryptococcus neoformans. Our metabolite analysis revealed that Cir1 influences the glycolytic pathway, ergosterol biosynthesis and inositol metabolism, which require numerous iron-dependent enzymes and play important roles in pathogenesis and antifungal sensitivity of the fungus. Moreover, we demonstrated that increased cellular iron content and altered gene expression in the cir1 mutant contributed to metabolite changes. Our study provides a new insight into iron regulation and the role of Cir1 in metabolome of C. neoformans.
Department of Bioscience and Biotechnology, Konkuk University, Seoul, Republic of Korea.
Jung Nam
JN
Choi
Jeongmi
J
Kim
Jiyoung
J
Kim
Won Hee
WH
Jung
Choong Hwan
CH
Lee
D000935:Antifungal Agents / Q000494:pharmacology; D001393:Azoles / Q000494:pharmacology; D003455:Cryptococcus neoformans / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D016002:Discriminant Analysis; D004875:Ergosterol / Q000096:biosynthesis; D005656:Fungal Proteins / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D007294:Inositol / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D035925:Iron-Regulatory Proteins / Q000378:metabolism; D016018:Least-Squares Analysis; D013058:Mass Spectrometry; D055442:Metabolome / Q000187:drug effects; D055432:Metabolomics; D008826:Microbial Sensitivity Tests; D009154:Mutation / Q000235:genetics; D025341:Principal Component Analysis
D000935:Antifungal Agents; D001393:Azoles; D005656:Fungal Proteins; D035925:Iron-Regulatory Proteins; D007294:Inositol; D007501:Iron; D004875:Ergosterol