Transcriptional profiling of Candida glabrata during phagocytosis by neutrophils and in the infected mouse spleen
Open accessAbstract
Expression microarray analysis of Candida glabrata following phagocytosis by human neutrophils was performed, and results were compared with those from C. glabrata incubated under conditions of carbohydrate or nitrogen deprivation. Twenty genes were selected to represent the major cell processes altered by phagocytosis or nutrient deprivation. Quantitative real-time PCR (qRT-PCR) with TaqMan chemistry was used to assess expression of the same genes in spleens of mice infected intravenously with Candida glabrata. The results in spleen closely paralleled gene expression in neutrophils or following carbohydrate deprivation. Fungal cells responded by upregulating alternative energy sources through gluconeogenesis, glyoxylate cycle, and long-chain fatty acid metabolism. Autophagy was likely employed to conserve intracellular resources. Aspartyl protease upregulation occurred and may represent defense against attacks on cell wall integrity. Downregulated genes were in the pathways of protein and ergosterol synthesis. Upregulation of the sterol transport gene AUS1 suggested that murine cholesterol may have been used to replace ergosterol, as has been reported in vitro. C. glabrata isolates in spleens of gp91(phox-/-) knockout mice with reduced oxidative phagocyte defenses were grossly similar although with a reduced level of response. These results are consistent with reported results of other fungi responding to phagocytosis, indicating that a rapid shift in metabolism is required for growth in a carbohydrate-limited intracellular environment.
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CgYPS genes are regulated by various environmental conditions including low pH, thermal stress, macrophage and neutrophil internalization.
“CgYPS genes have been shown to be regulated by various environmental conditions including low pH, thermal stress, macrophage and neutrophil internalization [60,61,62,63].”
From Candida glabrata: A Lot More Than Meets the Eye (2019) · cites this paper as [63]
The response of C. glabrata to the neutrophil environment involves upregulation of genes involved in oxidative stress, gluconeogenesis, glyoxylate cycle, and methionine metabolism.
“The response of C. glabrata to the neutrophil environment has also been studied with genes involved in oxidative stress, gluconeogenesis, glyoxylate cycle, and methionine metabolism displaying upregulation [63].”
From Candida glabrata: A Lot More Than Meets the Eye (2019) · cites this paper as [63]
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- Authors
- Fukuda, Y., Tsai, H.-F., Myers, T. G., & Bennett, J. E.
- Affiliations
- Clinical Mycology Section, Laboratory of Clinical Infectious Diseases, Bethesda, Maryland, USA
- National Institutes of Health (US)
- Venue
- Infection and Immunity
- Publisher
- American Society for Microbiology
- Published
- 2013-04
- Volume
- 81
- Issue
- 4
- Pages
- 1325-1333
- ISSN
- 0019-9567 (ISSN-L)
- 1098-5522
- PMC
- PMC3639592
- OpenAlex
- W2100445062
- Cited by
- 41
- References
- 34
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 5 · 2020: 4 · 2019: 7 · 2017: 1 · 2016: 3 · 2015: 5 · 2014: 4 · 2013: 3
- FWCI
- 3.65
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Infection and Immunity (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Keywords
- Candida glabrata, phagocytosis, neutrophils, fungal gene expression, nitrogen starvation, gluconeogenesis, glyoxylate cycle, long-chain fatty acid metabolism, autophagy, aspartic protease, ergosterol biosynthesis, sterol transport, spleen infection
- MeSH terms
- Animals, Candidiasis, Disease Models, Animal, Female, Humans, Mice, Inbred C57BL, Neutrophils, Phagocytosis, Spleen, Mice, Knockout, Gene Expression Profiling, Candida glabrata, Microarray Analysis, Mice, Real-Time Polymerase Chain Reaction
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