Biochemical Characterization of Recombinant Enterococcus faecalis EntV Peptide to Elucidate Its Antihyphal and Antifungal Mechanisms against Candida albicans .

التفاصيل البيبلوغرافية
العنوان:	Biochemical Characterization of Recombinant Enterococcus faecalis EntV Peptide to Elucidate Its Antihyphal and Antifungal Mechanisms against Candida albicans .
المؤلفون:	Fong JL; School of Chemistry, Chemical Engineering and Biotechnology (CCEB), Nanyang Technological University (NTU), 21 Nanyang Link, Singapore 637371, Singapore., Ong Eng Yong V; Temasek Life Sciences Laboratory, 1 Research Link, Singapore 117604, Singapore., Yeo C; School of Chemistry, Chemical Engineering and Biotechnology (CCEB), Nanyang Technological University (NTU), 21 Nanyang Link, Singapore 637371, Singapore., Adamson C; School of Chemistry, Chemical Engineering and Biotechnology (CCEB), Nanyang Technological University (NTU), 21 Nanyang Link, Singapore 637371, Singapore., Li L; School of Chemistry, Chemical Engineering and Biotechnology (CCEB), Nanyang Technological University (NTU), 21 Nanyang Link, Singapore 637371, Singapore., Zhang D; Temasek Life Sciences Laboratory, 1 Research Link, Singapore 117604, Singapore., Qiao Y; School of Chemistry, Chemical Engineering and Biotechnology (CCEB), Nanyang Technological University (NTU), 21 Nanyang Link, Singapore 637371, Singapore.
المصدر:	ACS infectious diseases [ACS Infect Dis] 2024 Sep 13; Vol. 10 (9), pp. 3408-3418. Date of Electronic Publication: 2024 Aug 13.
نوع المنشور:	Journal Article
اللغة:	English
بيانات الدورية:	Publisher: ACS Publications Country of Publication: United States NLM ID: 101654580 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2373-8227 (Electronic) Linking ISSN: 23738227 NLM ISO Abbreviation: ACS Infect Dis Subsets: MEDLINE
أسماء مطبوعة:	Original Publication: Washington, DC : ACS Publications, [2015]-
مواضيع طبية MeSH:	Candida albicans/drug effects , Enterococcus faecalis/drug effects , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Hyphae/drug effects , Hyphae/growth & development, Recombinant Proteins/pharmacology ; Recombinant Proteins/genetics ; Bacteriocins/pharmacology ; Bacteriocins/chemistry ; Microbial Sensitivity Tests ; Humans ; Fungal Proteins/genetics ; Fungal Proteins/metabolism ; Fungal Proteins/chemistry ; Endocytosis/drug effects
مستخلص:	Candida albicans is a common opportunistic fungus in humans, whose morphological switch between yeast and hyphae forms represents a key virulence trait. Developing strategies to inhibit C. albicans hyphal growth may provide insights into designs of novel antivirulent therapeutics. Importantly, the gut commensal bacterium, Enterococcus faecalis , secretes a bacteriocin EntV which has potent antivirulent and antifungal effects against C. albicans in infection models; however, hampered by the challenges to access large quantities of bioactive EntV, the detailed understanding of its mechanisms on C. albicans has remained elusive. In this work, we biochemically reconstituted the proteolytic cleavage reaction to obtain recombinant EntV ⁸⁸ -His 6 on a large preparative scale, providing facile access to the C-terminal EntV construct. Under in vitro C. albicans hyphal assay with specific inducers, we demonstrated that EntV ⁸⁸ -His 6 exhibits potent bioactivity against GlcNAc-triggered hyphal growth. Moreover, with fluorescent FITC-EntV ⁸⁸ -His 6 , we revealed that EntV ⁸⁸ -His 6 enters C. albicans via endocytosis and perturbs the proper localization of the polarisome scaffolding Spa2 protein. Our findings provide important clues on EntV's mechanism of action. Surprisingly, we showed that EntV ⁸⁸ -His 6 does not affect C. albicans yeast cell growth but potently exerts cytotoxicity against C. albicans under hyphal-inducing conditions in vitro . The combination of EntV ⁸⁸ -His 6 and GlcNAc displays rapid killing of C. albicans , rendering it a promising antivirulent and antifungal agent.
فهرسة مساهمة:	Keywords: Candida albicans; antifungal; bioactive EntV; fluorescent tagging; hyphal inhibition; in vitro proteolytic cleavage
المشرفين على المادة:	0 (Antifungal Agents) 0 (Recombinant Proteins) 0 (Bacteriocins) 0 (Fungal Proteins)
تواريخ الأحداث:	Date Created: 20240813 Date Completed: 20240913 Latest Revision: 20240913
رمز التحديث:	20240916
DOI:	10.1021/acsinfecdis.4c00515
PMID:	39137394
قاعدة البيانات:	MEDLINE

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تدمد:	2373-8227
DOI:	10.1021/acsinfecdis.4c00515