瑞士巴塞尔罗氏创新中心Kenneth A. Bradley和Michael A. Lobritz共同合作，近期取得重要工作进展。他们研究发现了一类针对脂多糖转运体的新型抗生素。相关研究成果2024年1月3日在线发表于《自然》上。
据介绍，耐碳青霉烯的鲍曼不动杆菌（CRAB）已成为一种主要的全球病原体，其治疗方案选择有限。鲍曼尼病在50多年前就已经感染了患者。
研究人员报道了对CRAB具有强大抗菌活性的栓系大环肽（MCP）抗生素的鉴定和优化。这类分子的作用机制包括通过抑制LptB2FGC复合物，阻断细菌脂多糖从内膜到外膜的运输。一种来源于MCP类的临床候选药物，zosurabalpin（RG6006），在体外和小鼠感染模型中有效治疗具有高度耐药性的当代CRAB分离株，克服了现有的抗生素耐药性机制。
总之，这一化学类别代表了一种很有前景的治疗模式，适用于目前治疗方案不足的CRAB侵袭性感染患者，并将LptB2FGC确定为抗菌药物开发的一个易处理靶点。
附：英文原文
Title: A novel antibiotic class targeting the lipopolysaccharide transporter
Author: Zampaloni, Claudia, Mattei, Patrizio, Bleicher, Konrad, Winther, Lotte, Thte, Claudia, Bucher, Christian, Adam, Jean-Michel, Alanine, Alexander, Amrein, Kurt E., Baidin, Vadim, Bieniossek, Christoph, Bissantz, Caterina, Boess, Franziska, Cantrill, Carina, Clairfeuille, Thomas, Dey, Fabian, Di Giorgio, Patrick, du Castel, Pauline, Dylus, David, Dzygiel, Pawel, Felici, Antonio, Garca-Alcalde, Fernando, Haldimann, Andreas, Leipner, Matthew, Leyn, Semen, Louvel, Sverine, Misson, Pauline, Osterman, Andrei, Pahil, Karanbir, Rigo, Sbastien, Schublin, Adrian, Scharf, Sebastian, Schmitz, Petra, Stoll, Theodor, Trauner, Andrej, Zoffmann, Sannah, Kahne, Daniel, Young, John A. T., Lobritz, Michael A., Bradley, Kenneth A.
Issue&Volume: 2024-01-03
Abstract: Carbapenem-resistant Acinetobacter baumannii (CRAB) has emerged as a major global pathogen with limited treatment options1. No new antibiotic chemical class with activity against A. baumannii has reached patients in over 50years1. Here we report the identification and optimization of tethered macrocyclic peptide (MCP) antibiotics with potent antibacterial activity against CRAB. The mechanism of action of this molecule class involves blocking the transport of bacterial lipopolysaccharide from the inner membrane to its destination on the outer membrane, through inhibition of the LptB2FGC complex. A clinical candidate derived from the MCP class, zosurabalpin (RG6006), effectively treats highly drug-resistant contemporary isolates of CRAB both in vitro and in mouse models of infection, overcoming existing antibiotic resistance mechanisms. This chemical class represents a promising treatment paradigm for patients with invasive infections due to CRAB, for whom current treatment options are inadequate, and additionally identifies LptB2FGC as a tractable target for antimicrobial drug development.
DOI: 10.1038/s41586-023-06873-0
Source: https://www.nature.com/articles/s41586-023-06873-0
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
