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

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.

SUBMITTER: Cruz MR

PROVIDER: S-EPMC9562342 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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

Cruz Melissa R MR Cristy Shane S Guha Shantanu S De Cesare Giuseppe Buda GB Evdokimova Elena E Sanchez Hiram H Borek Dominika D Miramón Pedro P Yano Junko J Fidel Paul L PL Savchenko Alexei A Andes David R DR Stogios Peter J PJ Lorenz Michael C MC Garsin Danielle A DA

Nature communications 20221013 1

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 indi ...[more]

PMID: 36229448

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

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

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