Cited by 30Antimicrobial Peptides and ActivitiesMicrobial Natural Products and BiosynthesisAntifungal resistance and susceptibility

Structural and functional analysis of EntV reveals a 12 amino acid fragment protective against fungal infections

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Cruz, Melissa R., Cristy, Shane, Guha, Shantanu, De Cesare, Giuseppe Buda, Evdokimova, Elena, Sanchez, Hiram, Borek, Dominika, Miramón, Pedro +7 more·2022·Nature Communications

Abstract

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].”

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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.
Venue
Nature Communications
Published
2022-10-13
Volume
13
Issue
1
Pages
6047-6047
ISSN
2041-1723 (ISSN-L)
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
Locations
  • 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

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