The ER-Mitochondria Encounter Structure Contributes to Hyphal Growth, Mitochondrial Morphology and Virulence of the Pathogenic Mold Aspergillus fumigatus

Geißel, Bernadette; Penka, Mirjam; Neubauer, Michael; Wagener, Johannes

doi:10.1016/j.ijmm.2016.11.005

Cited by 27Fungal and yeast genetics researchMitochondrial Function and PathologyAntifungal resistance and susceptibility

The ER-Mitochondria Encounter Structure Contributes to Hyphal Growth, Mitochondrial Morphology and Virulence of the Pathogenic Mold Aspergillus fumigatus

Geißel, Bernadette, Penka, Mirjam, Neubauer, Michael, Wagener, Johannes·2017·International Journal of Medical Microbiology

DOI 10.1016/j.ijmm.2016.11.005

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Abstract

Aspergillus fumigatus is an opportunistic fungal pathogen and the primary causative species of invasive aspergillosis, a systemic disease associated with high mortality rates. Treatment of invasive fungal infection relies on a very limited number of antifungal drug classes. In order to extend the spectrum of antifungal drugs novel target structures have to be identified. The ER-mitochondria encounter structure (ERMES), a recently discovered tether that links mitochondria and endoplasmic reticulum, is a potential drug target based on its absence in Metazoa. Very recently, it was shown that ERMES is important for the fitness and immune evasion of the pathogenic yeast Candida albicans. We studied the role of the four ERMES core components Mdm10, Mdm12, Mdm34 and Mmm1 in the pathogenic mold A. fumigatus. By construction and characterizing conditional mutants of all four core components and deletion mutants of mdm10 and mdm12, we show that each component is of significant importance for growth of the fungal pathogen. While markedness of the individual mutant phenotypes differed slightly, all components are important for maintenance of the mitochondrial morphology and the intra-organellar distribution of nucleoids. Characterization of the Mmm1 ERMES mutant in a Galleria mellonella infection model indicates that ERMES contributes to virulence of A. fumigatus. Our results demonstrate that pharmacologic inhibition of ERMES could exert antifungal activity against this important pathogen.

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The ERMES complex was found to be involved in Candida albicans and Aspergillus fumigatus pathogenicity, suggesting its potential as a target for new antifungal drugs.
“The ERMES complex was found to be involved in C. albicans and A. fumigatus pathogenicity, suggesting its potential as a target for new antifungal drugs [34,35,36].”
From In Candida glabrata, ERMES Component GEM1 Controls Mitochondrial Morphology, mtROS, and Drug Efflux Pump Expression, Resulting in Azole Susceptibility (2023) · cites this paper as [36]

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Authors: Geißel, B., Penka, M., Neubauer, M., & Wagener, J.
Affiliations: Max-von-Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie (DE)
Corresponding author: Wagener, Johannes
ORCID: Wagener, Johannes
Venue: International Journal of Medical Microbiology
Publisher: Elsevier BV
Published: 2017-01
Volume: 307
Issue: 1
Pages: 37-43
ISSN: 1438-4221 (ISSN-L)
DOI: 10.1016/j.ijmm.2016.11.005
OpenAlex: W2553964501
Cited by: 27
References: 24
Citations by year: 2026: 1 · 2025: 4 · 2024: 3 · 2023: 1 · 2022: 3 · 2021: 4 · 2020: 1 · 2019: 4 · 2018: 2 · 2017: 4
FWCI: 1.73
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: International Journal of Medical Microbiology (publishedVersion)
PubMed (publishedVersion)
Funders: Broad Institute
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
Keywords: ERMES, Aspergillus fumigatus, invasive aspergillosis, mitochondrial morphology, hyphal growth, fungal virulence, antifungal drug targets, Galleria mellonella infection model, conditional mutants
MeSH terms: Animals, Aspergillosis, Aspergillus fumigatus, Disease Models, Animal, Endoplasmic Reticulum, Fungal Proteins, Lepidoptera, Mitochondria, Mutation, Virulence, Hyphae, Gene Knockout Techniques

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The ER-Mitochondria Encounter Structure Contributes to Hyphal Growth, Mitochondrial Morphology and Virulence of the Pathogenic Mold Aspergillus fumigatus

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