Ab binding alters gene expression in Cryptococcus neoformans and directly modulates fungal metabolism
Open accessAbstract
Abs facilitate humoral immunity via the classical mechanisms of opsonization, complement activation, Ab-dependent cellular cytotoxicity, and toxin/viral neutralization. There is also evidence that some Abs mediate direct antimicrobial effects. For example, Ab binding to the polysaccharide capsule of the human pathogenic fungus Cryptococcus neoformans promotes opsonization but also inhibits polysaccharide release and biofilm formation. To investigate whether Ab binding affects C. neoformans directly, we analyzed fungal gene expression after binding of protective and nonprotective mAbs. The 2 IgM Abs and 1 IgG1 Ab tested each induced different changes in gene expression. The protective IgG1 mAb upregulated genes encoding proteins involved in fatty acid synthesis, the protective IgM mAb downregulated genes encoding proteins required for protein translation, and the nonprotective IgM mAb had modest effects on gene expression. Differences in gene expression correlated with mAb binding to different locations of the capsule. Of the 3 Abs tested, the protective IgG1 mAb bound to C. neoformans closest to the cell wall, produced specific differences in the pattern of phosphorylated proteins, caused changes in lipid metabolism, and resulted in increased susceptibility to the antifungal drug amphotericin B. These results suggest what we believe to be a new mode of action for Ab-mediated immunity and raise the possibility that immunoglobulins mediate cross talk between microbes and hosts through their effects on microbial metabolism.
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18B7 modulates C. neoformans gene expression and metabolism, resulting in increased susceptibility to antifungal drugs.
“18B7 is capable of modulating C. neoformans gene expression and metabolism, resulting in increased susceptibility to antifungal drugs130.”
From Treatment strategies for cryptococcal infection: challenges, advances and future outlook (2021) · cites this paper as [130]
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- Maxson ME, Dadachova E, Casadevall A, Zaragoza O. Radial mass density, charge, and epitope distri- bution in the Cryptococcus neoformans capsule. Eukaryot Cell. 2007;6(1):95-109.
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- Authors
- McClelland, E. E., Nicola, A. M., Prados-Rosales, R., & Casadevall, A.
- Affiliations
- Geisinger College of Health Sciences (US)
- Albert Einstein College of Medicine (US)
- Corresponding author
- McClelland, Erin E.
- Venue
- Journal of Clinical Investigation
- Published
- 2010-04-01
- Volume
- 120
- Issue
- 4
- Pages
- 1355-1361
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC2846037
- OpenAlex
- W2141967665
- Cited by
- 101
- References
- 39
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 3 · 2022: 6 · 2021: 4 · 2020: 5 · 2019: 5 · 2018: 12 · 2017: 7 · 2016: 10 · 2015: 7 · 2014: 7 · 2013: 10 · 2012: 10
- FWCI
- 6.98
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Washington University in St. Louis
- National Institutes of Health (5r01hl059842-23, 5r01ai052733-16, AI033142, HL059842-08, HL059842, 5r37ai033142-24)
- National Heart, Lung, and Blood Institute (R01-HL059842, HL059842-08)
- National Institute of Allergy and Infectious Diseases (AI-033774, R01AI033142, R37-AI033142, AI033142, R01-AI052733, R01AI033774)
- Topics
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Keywords
- Cryptococcus neoformans, antibody binding, monoclonal antibodies, fungal gene expression, polysaccharide capsule, IgG1, IgM, fatty acid synthesis, mRNA translation, lipid metabolism, phosphoproteins, amphotericin B susceptibility, fungal metabolism, host-pathogen interaction
- MeSH terms
- Amphotericin B, Antibodies, Fungal, Antibodies, Monoclonal, Cryptococcus neoformans, Gene Expression Regulation, Fungal, Bacterial Capsules, Lipid Metabolism
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