Candida albicans Hyr1p Confers Resistance to Neutrophil Killing and Is a Potential Vaccine Target
Open accessAbstract
Candida albicans is the most common cause of invasive fungal infections in humans. It is unclear how C. albicans escapes from phagocytic attack and survives in the hostile blood environment during life-threatening systemic infections. Using a conditional overexpression or suppression genetic strategy, we discovered that HYR1 gene reduced phagocytic killing activity of C. albicans in vitro and increased tissue fungal burden in vivo. Concordant with its positive regulation by the transcription factor Bcr1p, autonomous expression of HYR1 complemented the hypersusceptibility to phagocyte-mediated killing of a bcr1 null mutant of C. albicans in vitro. As for C. albicans, heterologous expression of HYR1 in Candida glabrata rendered the organism more resistant to neutrophil killing activity. Vaccination with a recombinant Hyr1p significantly protected mice against hematogenously disseminated candidiasis (P = .001). Finally, anti-rHyr1p polyclonal antibodies enhanced mouse neutrophil killing activity by directly neutralizing rHyr1p effects in vitro. Thus, Hyr1 is an important virulence factor for C. albicans, mediating resistance to phagocyte killing. Hyr1p is a promising target for vaccine or other immunological or small molecule intervention to improve the outcomes of disseminated candidiasis.
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Hyr1 is a hyphal-specific protein that inhibits C. albicans killing by neutrophils and contributes to virulence in mouse models of disseminated candidiasis and OPC.
“This hyphal-specific protein has previously been found to inhibit C. albicans killing by neutrophils and contribute to virulence in mouse models of both disseminated candidiasis and OPC, but its host cell receptor was unknown [24,25].”
From Candida albicans stimulates formation of a multi-receptor complex that mediates epithelial cell invasion during oropharyngeal infection (2023) · cites this paper as [24]
The Results report that HYR1 expression reduced neutrophil-mediated killing in vitro and increased fungal burden in the liver and spleen of mice with hematogenously disseminated candidiasis. The paper describes HYR1 as hypha-associated, but the passages do not address a mouse model of OPC; that part of the claim is not supported by this source. (LLM, conf=0.88)
Experimental — accuracy not yet measuredHyr1 enables C. albicans to resist killing by neutrophils.
“Previously, it was discovered that Hyr1 enables C. albicans to resist killing by neutrophils [24]. We verified this result with human neutrophils using hyr1Δ/Δ mutants constructed in both the SC5314 and SN250 strain backgrounds (Figs 8A and S5A).”
From Candida albicans stimulates formation of a multi-receptor complex that mediates epithelial cell invasion during oropharyngeal infection (2023) · cites this paper as [24]
Hyr1 contributes to virulence by enabling C. albicans to resist being killed by neutrophils.
“Hyr1 has been found to contribute to virulence by enabling C. albicans to resist being killed by neutrophils [24].”
From Candida albicans stimulates formation of a multi-receptor complex that mediates epithelial cell invasion during oropharyngeal infection (2023) · cites this paper as [24]
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- Authors
- Luo, G., Ibrahim, A. S., Spellberg, B., Nobile, C. J., Mitchell, A. P., & Fu, Y.
- Affiliations
- The Lundquist Institute (US)
- University of California, Los Angeles (US)
- University of California, San Francisco (US)
- Carnegie Mellon University (US)
- Corresponding author
- Fu, Yue
- Venue
- The Journal of Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-06
- Volume
- 201
- Issue
- 11
- Pages
- 1718-1728
- ISSN
- 0022-1899 (ISSN-L)
- 1537-6613
- PMC
- PMC3933264
- OpenAlex
- W2049091194
- Cited by
- 125
- References
- 2
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 11 · 2023: 11 · 2022: 6 · 2021: 5 · 2020: 4 · 2019: 4 · 2018: 5 · 2017: 7 · 2016: 5 · 2015: 10 · 2014: 8 · 2013: 5 · 2012: 14
- FWCI
- 8.50
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Infectious Diseases (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R03AI083251, R01AI067703, R21AI066010)
- 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, phagocytosis, virulence factors, vaccine targets, systemic candidiasis, Candida glabrata, antibody neutralization, invasive fungal infections
- MeSH terms
- Animals, Candida albicans, Fungal Proteins, Fungal Vaccines, Liver, Mice, Inbred C57BL, Neutrophils, Spleen, Colony Count, Microbial, Survival Analysis, Virulence Factors, Microbial Viability, Mice
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