Spore Germination of Pathogenic Filamentous Fungi

Sephton-Clark, Poppy; Voelz, Kerstin

doi:10.1016/bs.aambs.2017.10.002

Cited by 61 publications

(39 citation statements)

References 201 publications

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“…Germination cues can include, but are not limited to, the introduction of nutrients, the presence of light, temperature modulation, changes in osmolarity, pH shifts, the removal of dormancy factors, and the introduction of extracellular signaling molecules ( 5 – 15 ). Once germination is initiated, spores begin to swell and take up water.…”

Section: Introductionmentioning

confidence: 99%

Pathways of Pathogenicity: Transcriptional Stages of Germination in the Fatal Fungal Pathogen Rhizopus delemar

Sephton-Clark

Muñoz

Ballou

et al. 2018

mSphere

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Germination is key to the growth of many organisms, including fungal spores. Mucormycete spores exist abundantly within the environment and germinate to form hyphae. These spores are capable of infecting immunocompromised individuals, causing the disease mucormycosis. Germination from spore to hyphae within patients leads to angioinvasion, tissue necrosis, and often fatal infections. This study advances our understanding of how spore germination occurs in the mucormycetes, identifying processes we may be able to inhibit to help prevent or treat mucormycosis.

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Section: Introductionmentioning

confidence: 99%

Pathways of Pathogenicity: Transcriptional Stages of Germination in the Fatal Fungal Pathogen Rhizopus delemar

Sephton-Clark

Muñoz

Ballou

et al. 2018

mSphere

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“…In addition to providing a fungus-specific drug target, germination provides a unique opportunity for the prevention of fungal disease. Spores are stressresistant cell types that are known infectious particles of many fungal pathogens and, in Cryptococcus, spores show distinct disease profiles within mammalian hosts compared to yeast (7,8,14). Antifungal agents that target all potential infectious cell types could be used to protect against fungal pathogens through prophylaxis.…”

Section: Discussionmentioning

confidence: 99%

Spore Germination as a Target for Antifungal Therapeutics

Ortiz

Huang

Hull

2019

Antimicrob Agents Chemother

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Spores are required for long-term survival of many organisms, including most fungi. For the majority of fatal human fungal pathogens, spore germination is the key process required to initiate vegetative growth and ultimately cause disease. Because germination is required for pathogenesis, the process could hold fungus-specific targets for new antifungal drug development. Compounds that inhibit germination could be developed into high-efficacy, low-toxicity drugs for use in the prevention and/or treatment of fungal spore-mediated diseases. To identify drugs with the ability to inhibit pathogenic fungal spore germination, we developed a novel luciferase-based germination assay, using spores of the meningitis-causing yeast Cryptococcus. We screened the L1300 Selleck Library of U.S Food and Drug Administration-approved drugs and identified 27 that inhibit germination. Of these, 22 inhibited both germination and yeast growth, and 21 have not been previously indicated for use in the treatment of fungal diseases. We quantitated the inhibition phenotypes of 10 specific germination/growth inhibitors in detail and tested one drug, the antiparasitic compound pentamidine, in our mouse intranasal model of cryptococcal infection. We discovered that pentamidine was effective at reducing lung fungal burdens when used in either prophylaxis (before infection) or treatment (after establishing an infection). Due to its efficacy in vivo and low intranasal toxicity, pentamidine is a lead candidate for repurposing for broader use as an antigerminant to prevent spore-mediated disease in immunocompromised patients. Not only does pentamidine provide an opportunity for prophylaxis against fungal spores, but it also provides proof of concept for targeting pathogenic spore germination for antifungal drug development.

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“…Thus, P. destructans conidia have relatively low natural germinability or they need specific cultivation conditions for germination. The germination process is a complex result of environmental and physiological factors 64 . Thus, we cannot foresee the germination efficiency of stressed conidia in nature.…”

Section: Methodsmentioning

confidence: 99%

Comparative eco-physiology revealed extensive enzymatic curtailment, lipases production and strong conidial resilience of the bat pathogenic fungus Pseudogymnoascus destructans

Veselská

Homutová

Fraile

et al. 2020

Sci Rep

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The genus Pseudogymnoascus encompasses soil psychrophilic fungi living also in caves. Some are opportunistic pathogens; nevertheless, they do not cause outbreaks. Pseudogymnoascus destructans is the causative agent of the white-nose syndrome, which is decimating cave-hibernating bats. We used comparative eco-physiology to contrast the enzymatic potential and conidial resilience of P. destructans with that of phylogenetically diverse cave fungi, including Pseudogymnoascus spp., dermatophytes and outdoor saprotrophs. Enzymatic potential was assessed by Biolog MicroArray and by growth on labelled substrates and conidial viability was detected by flow cytometry. Pseudogymnoascusdestructans was specific by extensive losses of metabolic variability and by ability of lipid degradation. We suppose that lipases are important enzymes allowing fungal hyphae to digest and invade the skin. Pseudogymnoascus destructans prefers nitrogenous substrates occurring in bat skin and lipids. Additionally, P. destructans alkalizes growth medium, which points to another possible virulence mechanism. Temperature above 30 °C substantially decreases conidial viability of cave fungi including P. destructans. Nevertheless, survival of P. destructans conidia prolongs by the temperature regime simulating beginning of the flight season, what suggests that conidia could persist on the body surface of bats and contribute to disease spreading during bats active season.

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Spore Germination of Pathogenic Filamentous Fungi

Cited by 61 publications

References 201 publications

Pathways of Pathogenicity: Transcriptional Stages of Germination in the Fatal Fungal Pathogen Rhizopus delemar

Pathways of Pathogenicity: Transcriptional Stages of Germination in the Fatal Fungal Pathogen Rhizopus delemar

Spore Germination as a Target for Antifungal Therapeutics

Comparative eco-physiology revealed extensive enzymatic curtailment, lipases production and strong conidial resilience of the bat pathogenic fungus Pseudogymnoascus destructans

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