[新發現] 抗生素的新希望 - Ruminococcin C？20191027

Ruminococcin C, a promising antibiotic produced by a human gut symbiont

Steve Chiumento, Clarisse Roblin, Sylvie Kieffer-Jaquinod, Sybille Tachon,

Chloé Leprètre, Christian Basset, Dwi Aditiyarini1, Hamza Olleik, Cendrine Nicoletti,

Olivier Bornet, Olga Iranzo, Marc Maresca, Renaud Hardré, Michel Fons, Thierry Giardina, Estelle Devillard, Françoise Guerlesquin, Yohann Couté, Mohamed Atta, Josette Perrier, Mickael Lafond, Victor Duarte

Abstract

A major public health challenge today is the resurgence of microbial infections caused by multidrug-resistant strains. Consequently, novel antimicrobial molecules are actively sought for development. In this context, the human gut microbiome is an under-explored potential trove of valuable natural molecules, such as the ribosomally-synthesized and post-translationally modified peptides (RiPPs). The biological activity of the sactipeptide subclass of RiPPs remains under-characterized. Here, we characterize an antimicrobial sactipeptide, Ruminococcin C1, purified from the caecal contents of rats mono-associated with Ruminococcus gnavus E1, a human symbiont. Its heterologous expression and post-translational maturation involving a specific sactisynthase establish a thioether network, which creates a double-hairpin folding. This original structure confers activity against pathogenic Clostridia and multidrug-resistant strains but no toxicity towards eukaryotic cells. Therefore, the Ruminococcin C1 should be considered as a valuable candidate for drug development and its producer strain R. gnavus E1 as a relevant probiotic for gut health enhancement.

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從人類腸道菌叢產生的潛力抗生素 - Ruminococcin C

摘要

現今人們的健康所面對的一大挑戰就是具有多重抗藥性的微生物感染的一再發生。為了因應此一現況，針對嶄新的抗生素分子的研究一直都很積極的進行中。在這樣的情況中，人類腸道的菌叢是一個有潛力，卻仍然探索不足的貴重天然分子礦場：例如由核酸醣小體生合成並且經由後轉譯修飾的生肽鏈（RiPPs）。在RiPPs中的肌肽類型生肽的生理功能仍然未曾被分析過。在此，我們分析了從人類腸道共生菌叢中，和大鼠盲腸中Ruminococcin gnavus E有關聯的菌種中，純化出來一個具抗生素效能的肌肽類生肽 -Ruminococcin C1。它的異質性表現與後轉譯修飾需要一個特別的肌肽生成酶並建立一個硫醚網路，最終創造一個雙髮夾的折疊。這個最初的構造給予了抵抗致病的梭俊屬細菌以及多重抗藥性的菌種，但是對於真核細胞沒有任何毒性。因此，Ruminococcin C1應該被當成一個珍貴的新藥研發的候選物質，而對於產生它的菌種 - R. gnavus E1應該被視為一個促進腸道健康的益菌。