The Hyr1 protein from the fungus Candida albicans is a cross kingdom immunotherapeutic target for Acinetobacter bacterial infection
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Different pathogens share similar medical settings and rely on similar virulence strategies to cause infections. We have previously applied 3-D computational modeling and bioinformatics to discover novel antigens that target more than one human pathogen. Active and passive immunization with the recombinant N-terminus of Candida albicans Hyr1 (rHyr1p-N) protect mice against lethal candidemia. Here we determine that Hyr1p shares homology with cell surface proteins of the multidrug resistant Gram negative bacterium, Acinetobacter baumannii including hemagglutinin (FhaB) and outer membrane protein A (OmpA). The A. baumannii OmpA binds to C. albicans Hyr1p, leading to a mixed species biofilm. Deletion of HYR1, or blocking of Hyr1p using polyclonal antibodies, significantly reduce A. baumannii binding to C. albicans hyphae. Furthermore, active vaccination with rHyr1p-N or passive immunization with polyclonal antibodies raised against specific peptide motifs of rHyr1p-N markedly improve survival of diabetic or neutropenic mice infected with A. baumannii bacteremia or pneumonia. Antibody raised against one particular peptide of the rHyr1p-N sequence (peptide 5) confers majority of the protection through blocking A. baumannii invasion of host cells and inducing death of the bacterium by a putative iron starvation mechanism. Anti-Hyr1 peptide 5 antibodies also mitigate A. baumannii /C. albicans mixed biofilm formation in vitro. Consistent with our bioinformatic analysis and structural modeling of Hyr1p, anti-Hyr1p peptide 5 antibodies bound to A. baumannii FhaB, OmpA, and an outer membrane siderophore binding protein. Our studies highlight the concept of cross-kingdom vaccine protection against high priority human pathogens such as A. baumannii and C. albicans that share similar ecological niches in immunocompromised patients.
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Hyr1 is a promising vaccine target for prevention of both C. albicans and Acinetobacter baumanii infections.
“Previous studies by our group indicate that Hyr1 is a promising vaccine target for prevention of both C. albicans and Acinetobacter baumanii infections [42–44].”
From Candida albicans stimulates formation of a multi-receptor complex that mediates epithelial cell invasion during oropharyngeal infection (2023) · cites this paper as [43]
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Noble, S. M., French, S., Kohn, L. A., Chen, V., & Johnson, A. D. (2010) · Nature Genetics · doi:10.1038/ng.605 · Cited by 678 · see citing works
Medically important bacterial-fungal interactions
Peleg, A. Y., Hogan, D. A., & Mylonakis, E. (2010) · Nature Reviews Microbiology · doi:10.1038/nrmicro2313 · Cited by 619 · see citing works
Functional and Structural Diversity in the Als Protein Family of Candida albicans
Sheppard, D. C., Yeaman, M. R., Welch, W. H., Phan, Q. T., Fu, Y., Ibrahim, A. S., Filler, S. G., Zhang, M., Waring, A. J., & Edwards, J. E. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m401929200 · Cited by 300 · cited 2× · see citing works
“aureus [42], there are relatively low degrees of sequence identity between Hyr1 and the identified template proteins.”
BackgroundSelf-citationLuo, G., Ibrahim, A. S., French, S. W., Edwards, J. E., & Fu, Y. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025909 · Cited by 62 · see citing works
Self-citationFu, Y., Phan, Q. T., Luo, G., Solis, N. V., Liu, Y., Cormack, B. P., Edwards, J. E., Ibrahim, A. S., & Filler, S. G. (2013) · Infection and Immunity · doi:10.1128/iai.00013-13 · Cited by 37 · cited 4× · see citing works
“The hyr1/hyr1 mutant, PLOS Pathogens | https://doi.org/10.1371/journal.ppat.1007056 May 10, 2018 15 / 25 and hyr1/hyr1+HYR1 complemented strains were made from SN250 [71] while als3/als3 mutant was originated from SC5314 [72].”
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Cited by
Sorted by citations
Anti-bacterial monoclonal antibodies: Next generation therapy against superbugs
Wang, H., Chen, D., & Lu, H. (2022) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-022-11989-w · Cited by 45 · see citing works
Phan, Q. T., Solis, N. V., Cravener, M. V., Swidergall, M., Lin, J., Huang, M. Y., Liu, H., Singh, S., Ibrahim, A. S., Mazzone, M., et al. (2023) · PLOS Pathogens · doi:10.1371/journal.ppat.1011579 · Cited by 29 · see citing works
Self-citation
- Authors
- Uppuluri, P., Lin, L., Alqarihi, A., Luo, G., Youssef, E. G., Alkhazraji, S., Yount, N. Y., Ibrahim, B. A., Bolaris, M. A., Edwards, J. E., Swidergall, M., Filler, S. G., Yeaman, M. R., & Ibrahim, A. S.
- Affiliations
- University of California, Los Angeles (US)
- Beni-Suef University (EG)
- Corresponding author
- Ibrahim, Ashraf S.
- ORCID
- Venue
- PLOS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2018-05-10
- Volume
- 14
- Issue
- 5
- Pages
- e1007056
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- PMC
- PMC5963808
- OpenAlex
- W2800960099
- Cited by
- 57
- References
- 5
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 4 · 2023: 11 · 2022: 12 · 2021: 8 · 2020: 4 · 2019: 7 · 2018: 1
- FWCI
- 3.78
- Type
- journal article
- Language
- en
- Update notices
- new_version (2018-05-22)
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS Pathogens (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Greater South Information System
- Funders
- National Institute of Allergy and Infectious Diseases (AI 119339; AI 063382)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
- Keywords
- Candida albicans, Acinetobacter baumannii, immunotherapy targets, recombinant antigen, passive immunization, active immunization, polymicrobial biofilms, iron starvation, candidemia, bacteremia, pneumonia, immunocompromised patients, multidrug resistance
- MeSH terms
- Acinetobacter, Acinetobacter Infections, Animals, Anti-Bacterial Agents, Antibodies, Bacterial, Bacteria, Bacterial Infections, Bacterial Outer Membrane Proteins, Bacterial Vaccines, Candida albicans, Fungal Proteins, Immunization, Passive, Immunotherapy, Mice, Inbred BALB C, Vaccination, Biofilms, Acinetobacter baumannii, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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