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.

Functional convergence of gliP and aspf1 in Aspergillus fumigatus pathogenicity

“…The majority of genes in the Δ gliP mutant were expressed at wild-type levels in vivo (Table S1). However, relative to the wild-type strain, the Δ gliP mutant had increased expression of zrfA , which specifies a zinc transporters, and of aspf2 , which is required for growth under zinc-limited conditions (Table 1) [30,31]. These genes were also significantly up-regulated when the nanoString data were normalized to the gpdA housekeeping gene.…”

Metal Complex Derivatives of Azole: a Study on Their Synthesis, Characterization, and Antibacterial and Antifungal Activities

“…Fusarium species are well known to be highly resistant to a variety of antifungals, including azoles, particularly fluconazole, 54 and these strains are also capable of resisting high concentrations of metals such as zinc. 55,56 The complexes that contained copper and cobalt showed more antifungal activity than the zinc complexes. The tested fungi appear to be zinc-tolerant.…”

Broadly Conserved Fungal Effector BEC1019 Suppresses Host Cell Death and Enhances Pathogen Virulence in Powdery Mildew of Barley (Hordeum vulgare L.) (Retracted)

“…Several Fusarium species are also observed, including causal agents of Fusarium head blight of barley and wheat (F. graminearum), and sudden death syndrome (F. virguliforme) of soybean. Among the BEC1019 homologs from animal pathogens and free-living fungi are the characterized proteins Pra1 from Candida albicans (Citiulo et al 2012), major allergen Asp F2 from Aspergillus fumigatus (Amich et al 2010), and Zps1 (Lamb et al 2001) from Saccharomyces cerevisiae. As of January 23, 2014, no hits were obtained from tBLASTn searches of BEC1019 in the sequences of the basidiomycete obligate biotrophs Puccinia graminis, P. striiformis, and P. recondita, however, a homolog was found in the basidiomycete corn smut pathogen, Ustilago maydis.…”