Investigation of the Function of Candida albicans Als3 by Heterologous Expression in Candida glabrata
Open accessAbstract
During hematogenously disseminated infection, blood-borne Candida albicans invades the endothelial cell lining of the vasculature to invade the deep tissues. Although the C. albicans Als3 invasin is critical for invasion and damage of endothelial cells in vitro , a C. albicans als3 Δ/Δ mutant has normal virulence in the mouse model of disseminated infection. We hypothesized that the contribution of Als3 to virulence is obscured by the presence of additional C. albicans invasins. To elucidate the in vivo function of Als3, we heterologously expressed C. albicans ALS3 in Candida glabrata , a yeast that lacks a close ALS3 ortholog and has low virulence in mice. We found that following intravenous inoculation into mice, the ALS3 -expressing strain preferentially trafficked to the brain, where it induced significantly elevated levels of myeloperoxidase, tumor necrosis factor, monocyte chemoattractant protein 1, and gamma interferon. Also, the ALS3 -expressing strain had enhanced adherence to and invasion of human brain microvascular endothelial cells in vitro , demonstrating a potential mechanism for ALS3 -mediated neurotropism. In addition, upon initiation of infection, the ALS3 -expressing strain had increased trafficking to the cortex of the kidneys. With prolonged infection, this strain persisted in the kidneys at significantly higher levels than the control strain but did not induce an elevated inflammatory response. Finally, the ALS3 -expressing strain had increased resistance to neutrophil killing in vitro . These results indicate that during disseminated infection, Als3 mediates initial trafficking to the brain and renal cortex and contributes to fungal persistence in the kidneys.
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C. glabrata cells engineered to express C. albicans Als3 have enhanced resistance to neutrophil killing.
“Previously, we found that C. glabrata cells that were engineered to express C. albicans Als3 had enhanced resistance to neutrophil killing, thus supporting this novel function of Als3 [41].”
From Candida albicans stimulates formation of a multi-receptor complex that mediates epithelial cell invasion during oropharyngeal infection (2023) · cites this paper as [41]
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- Authors
- Fu, Y., Phan, Q. T., Luo, G., Solis, N. V., Liu, Y., Cormack, B. P., Edwards, J. E., Ibrahim, A. S., & Filler, S. G.
- Affiliations
- University of California, Los Angeles (US)
- Johns Hopkins University (US)
- Venue
- Infection and Immunity
- Publisher
- American Society for Microbiology
- Published
- 2013-07
- Volume
- 81
- Issue
- 7
- Pages
- 2528-2535
- ISSN
- 0019-9567 (ISSN-L)
- 1098-5522
- PMC
- PMC3697595
- OpenAlex
- W2101796369
- Cited by
- 37
- References
- 0
- Citations by year
- 2026: 4 · 2025: 1 · 2023: 4 · 2022: 3 · 2021: 3 · 2020: 2 · 2019: 3 · 2018: 6 · 2017: 2 · 2015: 4 · 2014: 4 · 2013: 1
- FWCI
- 2.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Infection and Immunity (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (UL1TR000124)
- National Institute of Allergy and Infectious Diseases (R01AI019990, R01-AI19990, R01AI046223, R01AI054928, R01AI063382)
- National Center for Advancing Translational Sciences
- 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 albicans, ALS3, invasin, Candida glabrata, heterologous expression, systemic candidiasis, neurotropism, brain microvascular endothelial cells, renal cortex, fungal virulence, host immune response
- MeSH terms
- Animals, Brain, Candida albicans, Candidiasis, Cell Adhesion, Cell Line, Endocytosis, Fungal Proteins, Genes, Fungal, Humans, Inflammation, Kidney Cortex, Male, Mice, Inbred BALB C, Peroxidase, Neutrophils, Colony Count, Microbial, Gene Expression Regulation, Fungal, Interleukin-8, Protein Transport, Candida glabrata, Mice, Human Umbilical Vein Endothelial Cells
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