小柯机器人

美国麻省理工和哈佛大学Deborah T. Hung团队在研究中取得进展。他们揭示了耐碳青霉烯的肺炎克雷伯氏菌毒力和持久性的适应性进化。这一研究成果发表在2020年4月13日出版的《自然—医学》上。

研究人员揭示了耐碳青霉烯的肺炎克雷伯氏菌致病性的全球演变。在美国和欧洲，其导致细菌毒力和对碳青霉烯抗性的反复趋同进化，最早可追溯到2009年。

研究人员证明了肺炎克雷伯氏菌可以通过高频发生的功能获得和功能丧失突变这两个相反的感染程序增强其致病性。荚膜生物合成基因wzc中的单核苷酸多态性导致超荚膜产生，这赋予了其对吞噬作用的抗性，增强了在动物模型中的传播并增加了死亡率。

相比之下，破坏荚膜生物合成基因的突变会损害荚膜的产生，从而增加上皮细胞的侵袭、体外生物膜的形成以及尿路感染的持续性。在欧洲和美国，这两种类型的荚膜突变体已经反复和独立地出现，其中包括与血液感染有关的高荚膜突变体与与尿路感染有关的无荚膜突变体。在后一种情况下，耐药性肺炎克雷伯氏菌可以产生潜在不可治愈的持续性感染。

据悉，对碳青霉烯类耐药的肠杆菌科已成为全球最紧急的公共卫生威胁之一，它们对被称为“最后手段”的抗生素产生耐药。在美国和欧洲，耐碳青霉烯类菌株-肺炎克雷伯菌ST258的序列占主导地位，具有流行性并伴有高死亡率。

附：英文原文

Title: Adaptive evolution of virulence and persistence in carbapenem-resistant Klebsiella pneumoniae

Author: Christoph M. Ernst, Julian R. Braxton, Carlos A. Rodriguez-Osorio, Anna P. Zagieboylo, Li Li, Alejandro Pironti, Abigail L. Manson, Anil V. Nair, Maura Benson, Kaelyn Cummins, Anne E. Clatworthy, Ashlee M. Earl, Lisa A. Cosimi, Deborah T. Hung

Issue&Volume: 2020-04-13

Abstract: Among the most urgent public health threats is the worldwide emergence of carbapenem-resistant Enterobacteriaceae1,2,3,4, which are resistant to the antibiotic class of ‘last resort’. In the United States and Europe, carbapenem-resistant strains of the Klebsiella pneumoniae ST258 (ref. 5) sequence type are dominant, endemic6,7,8 and associated with high mortality6,9,10. We report the global evolution of pathogenicity in carbapenem-resistant K. pneumoniae, resulting in the repeated convergence of virulence and carbapenem resistance in the United States and Europe, dating back to as early as 2009. We demonstrate that K. pneumoniae can enhance its pathogenicity by adopting two opposing infection programs through easily acquired gain- and loss-of-function mutations. Single-nucleotide polymorphisms in the capsule biosynthesis gene wzc lead to hypercapsule production, which confers phagocytosis resistance, enhanced dissemination and increased mortality in animal models. In contrast, mutations disrupting capsule biosynthesis genes impair capsule production, which enhances epithelial cell invasion, in vitro biofilm formation and persistence in urinary tract infections. These two types of capsule mutants have emerged repeatedly and independently in Europe and the United States, with hypercapsule mutants associated with bloodstream infections and capsule-deficient mutants associated with urinary tract infections. In the latter case, drug-tolerant K. pneumoniae can persist to yield potentially untreatable, persistent infection.

DOI: 10.1038/s41591-020-0825-4

Source: https://www.nature.com/articles/s41591-020-0825-4

Nature Medicine：《自然—医学》，创刊于1995年。隶属于施普林格·自然出版集团，最新IF：87.241
官方网址：https://www.nature.com/nm/
投稿链接：https://mts-nmed.nature.com/cgi-bin/main.plex