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An Ex vivo Assay to Study Candida albicans Hyphal Morphogenesis in the Gastrointestinal Tract
Published on: July 1, 2020
Amino acids mediate colony and cell differentiation in the fungal pathogen Candida parapsilosis
Seong-Kyoun Kim1, Kamal El Bissati1, Choukri Ben Mamoun1
1Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, CT 06030-3301, USA.
Abstract:
Candida parapsilosis is responsible for severe cases of non-albicans systemic candidiasis and is one of the leading causes of mortality in neonates. The molecular mechanisms underlying this organism's virulence remain unknown. Unlike C. albicans, which can exist in several morphogenetic forms, C. parapsilosis exists in either the yeast or pseudohyphal forms. The environmental signals that trigger pseudohyphal differentiation and the signalling pathways that transduce these signals are unknown. This paper provides evidence for the role of amino acids in morphogenesis in C. parapsilosis. The cell and colony morphologies, pseudohyphal differentiation and invasive growth of five C. parapsilosis isolates were characterized in ammonium-rich minimal media lacking or supplemented with naturally occurring amino acids. C. parapsilosis underwent dramatic changes in cellular and colony morphology and formed pseudohyphae in response to a specific subset of amino acids. Transport studies showed that these amino acid inducers activate the transport of some, but not all, unrelated amino acids. Interestingly, citrulline, an amino acid that is not transported in the presence of ammonium, strongly induced pseudohyphal morphogenesis in C. parapsilosis under these conditions. Together the data suggest that amino acids are important morphogens in C. parapsilosis and that amino-acid-mediated morphogenesis in this organism does not require transport of the ligand across the plasma membrane.
Insights
Amino acids are key triggers for morphogenetic changes in Candida parapsilosis, a significant cause of neonatal infections. These findings shed light on the molecular mechanisms of this opportunistic fungus.
Area of Science:
- Mycology
- Medical Microbiology
- Molecular Biology
Background:
- Candida parapsilosis causes severe non-albicans systemic candidiasis, particularly in neonates, with high mortality.
- The molecular basis of C. parapsilosis virulence and its morphogenetic regulation are largely unknown.
- Unlike C. albicans, C. parapsilosis exhibits limited morphogenetic plasticity, primarily existing as yeast or pseudohyphae.
Purpose of the Study:
- To investigate the role of amino acids as environmental signals regulating morphogenesis in Candida parapsilosis.
- To characterize the impact of specific amino acids on cell and colony morphology, pseudohyphal differentiation, and invasive growth.
- To explore the relationship between amino acid transport and amino-acid-induced morphogenesis.
Main Methods:
- Culturing five C. parapsilosis isolates in ammonium-rich minimal media with and without various amino acids.
- Assessing changes in cellular and colony morphology and pseudohyphal formation.
- Conducting transport studies to evaluate the uptake of different amino acids under various conditions.
Main Results:
- Specific amino acids induced significant alterations in C. parapsilosis cell and colony morphology, promoting pseudohyphal differentiation.
- Amino acid inducers activated the transport of some, but not all, unrelated amino acids.
- Citrulline strongly induced pseudohyphal morphogenesis even when ammonium was present, despite not being transported under these conditions.
Conclusions:
- Amino acids function as critical morphogens in Candida parapsilosis.
- Amino-acid-mediated morphogenesis in C. parapsilosis can occur independently of direct amino acid transport across the plasma membrane.
- Understanding these pathways is crucial for developing targeted therapies against C. parapsilosis infections.
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