title: Aspergillus fumigatus survival in alkaline and extreme zinc-limiting environments relies on the induction of a zinc homeostasis system encoded by the zrfC and aspf2 genes.
abstract: Aspergillus fumigatus has three zinc transporter-encoding genes whose expression is regulated by both pH and the environmental concentration of zinc. We have previously reported that the zrfA and zrfB genes of A. fumigatus are transcribed at higher levels and are required for fungal growth under acidic zinc-limiting conditions whereas they are dispensable for growth in neutral or alkaline zinc-limiting media. Here we report that the transporter of the zinc uptake system that functions in A. fumigatus growing in neutral or alkaline environments is encoded by zrfC. The transcription of zrfC occurs divergently with respect to the adjacent aspf2 gene, which encodes an immunodominant antigen secreted by A. fumigatus. The two genes-zrfC and aspf2-are required to different extents for fungal growth in alkaline and extreme zinc-limiting media. Indeed, these environmental conditions induce the simultaneous transcription of both genes mediated by the transcriptional regulators ZafA and PacC. ZafA upregulates the expression of zrfC and aspf2 under zinc-limiting conditions regardless of the ambient pH, whereas PacC represses the expression of these genes under acidic growth conditions. Interestingly, the mode of action of PacC for zrfC-aspf2 transcription contrasts with the more widely accepted model for PacC function, according to which under alkaline growth conditions PacC would activate the transcription of alkaline-expressed genes but would repress the transcription of acid-expressed genes. In sum, this report provides a good framework for investigating several important aspects of the biology of species of Aspergillus, including the repression of alkaline genes by PacC at acidic pH and the interrelationship that must exist between tissue pH, metal availability in the host tissue, and fungal virulence.
authors.affiliation: Instituto de Microbiología-Bioquímica, Centro mixto CSIC/USAL, Departamento de Microbiología y Genética (Universidad de Salamanca), 37007 Salamanca, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Amich
authors.forename: Rocío
authors.initials: R
authors.lastname: Vicentefranqueira
authors.forename: Fernando
authors.initials: F
authors.lastname: Leal
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Calera
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence; D001232:Aspergillus fumigatus / Q000187:drug effects / Q000502:physiology*; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D018076:DNA, Complementary / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D040461:Gene Components / Q000235:genetics; D017353:Gene Deletion; D015870:Gene Expression / Q000235:genetics; D015966:Gene Expression Regulation, Fungal / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014162:Transfection; D015854:Up-Regulation / Q000235:genetics; D015032:Zinc / Q000172:deficiency / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D027682:Cation Transport Proteins; D018076:DNA, Complementary; D005656:Fungal Proteins; C092394:PacC protein, Aspergillus; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C098750:ZRT1 protein, S cerevisiae; C101759:ZRT2 protein, S cerevisiae; C106810:allergen Asp f 2, Aspergillus fumigatus; D015032:Zinc