Structural and functional analysis of EntV reveals a 12 amino acid fragment protective against fungal infections
Open accessAbstract
Fungal pathogens are a continuing challenge due to few effective antifungals and a rise in resistance. In previous work, we described the inhibition of Candida albicans virulence following exposure to the 68 amino acid bacteriocin, EntV, secreted by Enterococcus faecalis. Here, to optimize EntV as a potential therapeutic and better understand its antifungal features, an X-ray structure is obtained. The structure consists of six alpha helices enclosing a seventh 16 amino acid helix (α7). The individual helices are tested for antifungal activity using in vitro and nematode infection assays. Interestingly, α7 retains antifungal, but not antibacterial activity and is also effective against Candida auris and Cryptococcus neoformans. Further reduction of α7 to 12 amino acids retains full antifungal activity, and excellent efficacy is observed in rodent models of C. albicans oropharyngeal, systemic, and venous catheter infections. Together, these results showcase EntV-derived peptides as promising candidates for antifungal therapeutic development.
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A shorter 12-mer peptide derived from EntV maintained inhibitory activity, including against Candida biofilms.
“In a recent study aimed at optimizing its potential anti-Candida therapeutic the authors identified a shorter 12-mer peptide derived from EntV which maintained the inhibitory activity, including against Candida biofilms [62].”
From Antifungal therapy of Candida biofilms: Past, present and future (2023) · cites this paper as [62]
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- Authors
- Cruz, M. R., Cristy, S., Guha, S., De Cesare, G. B., Evdokimova, E., Sanchez, H., Borek, D., Miramón, P., Yano, J., Fidel, P. L., Savchenko, A., Andes, D. R., Stogios, P. J., Lorenz, M. C., & Garsin, D. A.
- Affiliations
- The University of Texas Health Science Center at Houston (US)
- University of Toronto (CA)
- The University of Texas Southwestern Medical Center (US)
- Louisiana State University (US)
- University of Calgary (CA)
- University of Wisconsin–Madison (US)
- Corresponding author
- Lorenz, Michael C.
- Garsin, Danielle A.
- ORCID
- Venue
- Nature Communications
- Published
- 2022-10-13
- Volume
- 13
- Issue
- 1
- Pages
- 6047-6047
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC9562342
- OpenAlex
- W4304943561
- Cited by
- 30
- References
- 60
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 7 · 2023: 11 · 2022: 1
- FWCI
- 3.75
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
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- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Commons-TMC (Texas Medical Center) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- U.S. Department of Health & Human Services | National Institutes of Health (R01DE027608, R01AI073289, HHSN272201700060C, T32AI141349)
- Topics
- Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
- Health Sciences › Medicine › Pharmacology › Microbial Natural Products and Biosynthesis
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Keywords
- bacteriocins, Enterococcus faecalis, Candida albicans, antifungal peptides, Candida auris, Cryptococcus neoformans, oropharyngeal candidiasis, catheter-related infection, X-ray crystal structure, antifungal resistance
- MeSH terms
- Amino Acids, Antifungal Agents, Bacteriocins, Candida albicans, Cryptococcus neoformans, Humans, Microbial Sensitivity Tests, Mycoses
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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