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

• DOI: 10.1038/s41467-022-33613-1
• Publication Date: 2022-10-13T12:07:35Z
• Authors: Melissa R. Cruz; Shane Cristy; Shantanu Guha; Giuseppe Buda De ...; Elena Evdokimova; Hiram Sanchez; Dominika Borek; Pedro Miramón; Junko Yano; Paul L. Fidel; Alexei Savchenko; David R. Andes; Peter J. Stogios; Michael C. Lorenz; Danielle A. Garsin
• Keywords: Enterococcus faecalis

Abstract Fungal pathogens are a continuing challenge due to few effective antifungals and rise in resistance. In previous work, we described the inhibition of Candida albicans virulence following exposure 68 amino acid bacteriocin, EntV, secreted by Enterococcus faecalis . Here, optimize EntV as potential therapeutic better understand its antifungal features, an X-ray structure is obtained. The consists six alpha helices enclosing seventh 16 helix (α7). individual tested for activity using vitro nematode infection assays. Interestingly, α7 retains antifungal, but not antibacterial also against auris Cryptococcus neoformans Further reduction 12 acids full activity, excellent efficacy observed rodent models C. oropharyngeal, systemic, venous catheter infections. Together, these results showcase EntV-derived peptides promising candidates development.