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Published on: April 15, 2019
Molecular Mechanisms of Conidial Germination in Aspergillus spp
Tim J H Baltussen1,2, Jan Zoll3,2, Paul E Verweij3,2
1Department of Medical Microbiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands Tim.Baltussen@radboudumc.nl.
Abstract:
Aspergilli produce conidia for reproduction or to survive hostile conditions, and they are highly effective in the distribution of conidia through the environment. In immunocompromised individuals, inhaled conidia can germinate inside the respiratory tract, which may result in invasive pulmonary aspergillosis. The management of invasive aspergillosis has become more complex, with new risk groups being identified and the emergence of antifungal resistance. Patient survival is threatened by these developments, stressing the need for alternative therapeutic strategies. As germination is crucial for infection, prevention of this process might be a feasible approach. A broader understanding of conidial germination is important to identify novel antigermination targets. In this review, we describe conidial resistance against various stresses, transition from dormant conidia to hyphal growth, the underlying molecular mechanisms involved in germination of the most common Aspergillus species, and promising antigermination targets. Germination of Aspergillus is characterized by three morphotypes: dormancy, isotropic growth, and polarized growth. Intra- and extracellular proteins play an important role in the protection against unfavorable environmental conditions. Isotropically expanding conidia remodel the cell wall, and biosynthetic machineries are needed for cellular growth. These biosynthetic machineries are also important during polarized growth, together with tip formation and the cell cycle machinery. Genes involved in isotropic and polarized growth could be effective antigermination targets. Transcriptomic and proteomic studies on specific Aspergillus morphotypes will improve our understanding of the germination process and allow discovery of novel antigermination targets and biomarkers for early diagnosis and therapy.
Insights
Preventing Aspergillus conidial germination is key to fighting invasive pulmonary aspergillosis in immunocompromised patients. Understanding germination mechanisms can reveal novel antigermination targets for new therapies.
Area of Science:
- Mycology and Infectious Diseases
- Molecular Biology and Genetics
Background:
- Invasive pulmonary aspergillosis (IPA) is a serious threat to immunocompromised individuals, complicated by emerging antifungal resistance.
- Aspergillus conidia are reproductive spores that can germinate in the respiratory tract, initiating infection.
- Current treatment strategies for IPA are becoming less effective, necessitating the development of alternative therapeutic approaches.
Purpose of the Study:
- To review the current understanding of Aspergillus conidial germination, including resistance mechanisms and molecular pathways.
- To identify and discuss potential antigermination targets for novel therapeutic strategies against IPA.
- To highlight the importance of understanding germination for developing new diagnostic and therapeutic biomarkers.
Main Methods:
- Review of existing literature on Aspergillus conidial biology, stress resistance, and germination processes.
- Analysis of molecular mechanisms underlying the transition from dormant conidia to hyphal growth.
- Discussion of transcriptomic and proteomic data to identify potential therapeutic targets.
Main Results:
- Aspergillus germination involves three distinct morphotypes: dormancy, isotropic growth, and polarized growth.
- Intra- and extracellular proteins are crucial for conidial resistance to environmental stresses.
- Genes associated with isotropic and polarized growth represent promising targets for antigermination strategies.
Conclusions:
- Preventing conidial germination is a viable strategy to combat invasive aspergillosis.
- A deeper understanding of the molecular basis of germination will facilitate the discovery of novel antigermination targets.
- Further transcriptomic and proteomic studies are essential for identifying new therapeutic targets and diagnostic biomarkers for IPA.
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