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

Authors

• M.R. Cruz, The University of Texas Health Science Center at Houston, Houston, TX
• S. Cristy, The University of Texas Health Science Center at Houston, Houston, TX
• S. Guha, The University of Texas Health Science Center at Houston, Houston, TX
• G.B. De Cesare, The University of Texas Health Science Center at Houston, Houston, TX
• E. Evdokimova, University of Toronto, Toronto, ON
• H. Sanchez, University of Wisconsin, Madison, WI
• D. Borek, The University of Texas Southwestern Medical Center, Dallas, TX
• P. Miramón, The University of Texas Health Science Center at Houston, Houston, TX
• Junko Yano, LSU Health Sciences Center - New OrleansFollow
• Paul L. Fidel, LSU Health Sciences Center - New OrleansFollow
• A. Savchenko, University of Toronto, Toronto, ON
• D.R. Andes, University of Wisconsin, Madison, WI
• P.J. Stogios, University of Toronto, Toronto, ON
• M.C. Lorenz, The University of Texas Health Science Center at Houston, Houston, TX
• D.A. Garsin, The University of Texas Health Science Center at Houston, Houston, TX

Document Type

Article

Publication Date

10-13-2022

Publication Title

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.

PubMed ID

36229448

Volume

13

Issue

13

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Cruz, M.R.; Cristy, S.; Guha, S.; De Cesare, G.B.; Evdokimova, E.; Sanchez, H.; Borek, D.; Miramón, P.; Yano, Junko; Fidel, Paul L.; Savchenko, A.; Andes, D.R.; Stogios, P.J.; Lorenz, M.C.; and Garsin, D.A., "Structural and functional analysis of EntV reveals a 12 amino acid fragment protective against fungal infections" (2022). School of Dentistry Faculty Publications. 278.
https://digitalscholar.lsuhsc.edu/sod_facpubs/278
10.1038/s41467-022-33613-1