瑞士苏黎世联邦理工学院Wolf-Dietrich Hardt和Médéric Diard课题组合作，发现沙门氏菌会在肠道中促进抗生素耐药性质粒的传播。 相关论文2019年9月4日在线发表于《自然》。
他们研究了持留菌是否也可以促进抗性质粒的传播。与突变相反，抗性质粒的转移需要供体和受体细菌菌株的共同发生。为了研究该问题，研究人员选择了兼性细胞内肠道病原体鼠伤寒沙门氏菌（S. Typhimurium）和大肠杆菌（Escherichia coli），其属于共生微生物群。鼠伤寒沙门氏菌形成在几种宿主组织中抗生素治疗后存活的持留菌。研究显示，组织相关的鼠伤寒沙门氏菌持久性代表质粒供体或受体的长寿储库。鼠伤寒沙门氏菌宿主的储库的形成需要肠道相关组织中的沙门氏菌致病岛（SPI）-1和/或SPI-2，或系统部位的SPI-2。将这些持留菌重新接种到肠腔中使得供体与肠道驻留受体共同发生，从而有利于各种肠杆菌科菌株之间的质粒转移。研究者在重新播种后的两到三天内观察到高达99％的转接合子。数学模型显示，罕见的再播种事件可能足以达到高频率的共轭。在用鼠伤寒沙门氏菌口服感染以及随后的质粒转移后，疫苗接种减少了持留菌库的形成。研究人员发现，即使没有选择质粒编码的抗性基因，病原体持留菌的小储库也可以促进肠道中混杂的抗性质粒的传播。
据了解，通过突变或获得遗传物质（如抗性质粒）的抗生素抗性细菌，代表了一个主要的公共卫生问题。持留菌是通过可逆地调整生理机能，存活于抗生素中的细菌亚群，并且可以促进抗生素抗性突变体的出现。
附：英文原文
Title: Salmonella persisters promote the spread of antibiotic resistance plasmids in the gut
Author: Erik Bakkeren, Jana S. Huisman, Stefan A. Fattinger, Annika Hausmann, Markus Furter, Adrian Egli, Emma Slack, Mikael E. Sellin, Sebastian Bonhoeffer, Roland R. Regoes, Mdric Diard, Wolf-Dietrich Hardt
Issue&Volume: 2019-09-04
Abstract: The emergence of antibiotic-resistant bacteria through mutations or the acquisition of genetic material such as resistance plasmids represents a major public health issue. Persisters are subpopulations of bacteria that survive antibiotics by reversibly adapting their physiology, and can promote the emergence of antibiotic-resistant mutants. We investigated whether persisters can also promote the spread of resistance plasmids. In contrast to mutations, the transfer of resistance plasmids requires the co-occurrence of both a donor and a recipient bacterial strain. For our experiments, we chose the facultative intracellular entero-pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) and Escherichia coli, a common member of the microbiota. S. Typhimurium forms persisters that survive antibiotic therapy in several host tissues. Here we show that tissue-associated S. Typhimurium persisters represent long-lived reservoirs of plasmid donors or recipients. The formation of reservoirs of S. Typhimurium persisters requires Salmonella pathogenicity island (SPI)-1 and/or SPI-2 in gut-associated tissues, or SPI-2 at systemic sites. The re-seeding of these persister bacteria into the gut lumen enables the co-occurrence of donors with gut-resident recipients, and thereby favours plasmid transfer between various strains of Enterobacteriaceae. We observe up to 99% transconjugants within two to three days of re-seeding. Mathematical modelling shows that rare re-seeding events may suffice for a high frequency of conjugation. Vaccination reduces the formation of reservoirs of persisters after oral infection with S. Typhimurium, as well as subsequent plasmid transfer. We conclude thateven without selection for plasmid-encoded resistance genessmall reservoirs of pathogen persisters can foster the spread of promiscuous resistance plasmids in the gut.
DOI: 10.1038/s41586-019-1521-8
Source:https://www.nature.com/articles/s41586-019-1521-8
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
