Zinc and Microsporum canis: Targeting ZafA to Disrupt Fungal Virulence Original paper
Researched by:
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Karen Pendergrass
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Karen Pendergrass
Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease—four years before the first published case study.
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Microbes
Microbes
Microbes, short for microorganisms, are tiny living organisms that are ubiquitous in the environment, including on and inside the human body. They play a crucial role in human health and disease, functioning within complex ecosystems in various parts of the body, such as the skin, mouth, gut, and respiratory tract. The human microbiome, which is […]
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Microsporum canis (M. canis)
Microsporum canis (M. canis)
OverviewMicrosporum canis (M. canis) is a zoophilic dermatophyte common in cats and dogs, responsible for 90% of feline dermatophytoses worldwide.[1][2] It has significant zoonotic potential, transmitting to humans through fomites or direct animal contact, causing severe superficial mycosis. M. canis is considered anthropo-zoophilic and can infect pediatric or immunocompromised patients, causing severe inflammatory responses such […]
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Karen Pendergrass
Researched by:
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Karen Pendergrass
ID
Karen Pendergrass
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Karen Pendergrass
What was studied?
This study investigated the molecular and phenotypic impact of zinc deficiency on Microsporum canis, a dermatophyte responsible for zoonotic skin infections in humans and animals. Using RNA-Seq, researchers assessed transcriptomic changes in M. canis grown under zinc-restricted conditions and identified differentially expressed genes (DEGs). Particular focus was placed on the ZafA gene—a zinc-responsive transcription factor homologous to Zap1 in Saccharomyces cerevisiae—which was significantly upregulated under zinc-deficient conditions. Functional validation included construction of a ZafA knockout strain (ZafA-hph) via Agrobacterium tumefaciens-mediated transformation (ATMT), which allowed assessment of zinc absorption, growth, conidiation, pathogenicity, and gene expression regulation. This research delves deep into the impacts of zinc on Microsporum canis and sheds light on critical fungal dynamics.
Who was studied?
The study was conducted on Microsporum canis strain CBS 113480 in vitro and in vivo. Fungal strains were cultured under varying zinc conditions (0–1000 nM Zn²⁺), and both wild-type and ZafA-deficient strains were compared for phenotypic and transcriptional differences. In vivo pathogenicity was assessed using New Zealand rabbits, which were infected with wild-type or ZafA-hph strains for histopathological evaluation. This sheds light on how zinc and Microsporum canis interact to affect growth and pathogenic behaviors.
Most important findings
Zinc deficiency significantly impaired M. canis growth, reduced conidiation, and altered global gene expression. Key findings included:
| Finding | Description |
|---|---|
| ZafA gene role | ZafA was highly upregulated in zinc-deficient cultures and is required for zinc uptake, conidiation, and virulence. |
| ZafA-hph phenotype | Knockout strains exhibited reduced growth, absent conidia, and reduced zinc uptake (ICP-MS confirmed lower intracellular Zn²⁺). |
| Virulence loss | Rabbits infected with ZafA-hph showed minimal skin lesions compared to wild-type-infected animals. |
| Zinc transporter regulation | ZupT (MCYG_04486) and ZTR (MCYG_02504) were significantly downregulated in ZafA-deficient strains. |
| Major transcriptional shifts | 764 upregulated and 585 downregulated genes (Zn200 vs Norm); GO and KEGG analysis linked DEGs to zinc ion binding, oxidative stress response, and growth/metabolism pathways. |
These results confirm ZafA as a key regulator of zinc homeostasis, fungal physiology, and pathogenesis. The findings highlight the complex relationship between zinc and Microsporum canis, illustrating significant impacts on zinc uptake and genetic expression.
Key implications
This study demonstrates that zinc availability is critical for the growth and pathogenicity of M. canis, and that ZafA functions as a master transcriptional regulator of zinc uptake and associated pathways. The ZafA gene represents a promising antifungal drug target, as its disruption severely compromises fungal growth and virulence without affecting human homologs. By targeting ZafA or its downstream zinc transporters, novel antifungal therapies could be developed. Additionally, the work introduces a viable genetic manipulation technique (ATMT) for M. canis, facilitating further functional genomics research in dermatophytes. These insights are especially valuable for microbiome-targeted antifungal strategies, where disrupting fungal micronutrient acquisition can modulate microbial balance in skin and hair-associated niches. In summary, zinc and Microsporum canis interactions offer pathways for innovative antifungal therapies.
Zinc
Zinc is an essential trace element vital for cellular functions and microbiome health. It influences immune regulation, pathogen virulence, and disease progression in conditions like IBS and breast cancer. Pathogens exploit zinc for survival, while therapeutic zinc chelation can suppress virulence, rebalance the microbiome, and offer potential treatments for inflammatory and degenerative diseases.