小柯机器人

美国乔治亚理工学院Marvin Whiteley研究小组发现，一种铜绿假单胞菌小RNA调控慢性和急性感染。2023年5月24日，《自然》杂志在线发表了这项成果。

通过直接检查人源性样本中的细菌基因表达，研究人员发现了一个协调机会型病原体铜绿假单胞菌的慢性和急性感染之间转变的基因。这个基因的表达水平，被命名为sicX，是铜绿假单胞菌在人类慢性伤口和囊性纤维化感染中表达的最高的基因，但在标准的实验室生长过程中，它的表达水平极低。结果表明，sicX编码的小RNA被低氧条件强烈诱导，并在转录后调控厌氧泛醌的生物合成。在多种哺乳动物的感染模型中，删除sicX会导致铜绿假单胞菌从慢性生活方式转为急性生活方式。

值得注意的是，sicX也是这种从慢性到急性转变的生物标志物，因为当慢性感染分散到引起急性败血症时，它是最下调的基因。这项工作解决了几十年来关于铜绿假单胞菌从慢性到急性转换的分子基础的问题，并表明氧气是急性致死的主要环境驱动因素。

据悉，在不同生活方式之间转换的能力使细菌病原体能够在不同的生态环境中繁衍。然而，对它们在人类宿主体内的生活方式变化还缺乏分子了解。

附：英文原文

Title: A Pseudomonas aeruginosa small RNA regulates chronic and acute infection

Author: Cao, Pengbo, Fleming, Derek, Moustafa, Dina A., Dolan, Stephen K., Szymanik, Kayla H., Redman, Whitni K., Ramos, Anayancy, Diggle, Frances L., Sullivan, Christopher S., Goldberg, Joanna B., Rumbaugh, Kendra P., Whiteley, Marvin

Issue&Volume: 2023-05-24

Abstract: The ability to switch between different lifestyles allows bacterial pathogens to thrive in diverse ecological niches1,2. However, a molecular understanding of their lifestyle changes within the human host is lacking. Here, by directly examining bacterial gene expression in human-derived samples, we discover a gene that orchestrates the transition between chronic and acute infection in the opportunistic pathogen Pseudomonas aeruginosa. The expression level of this gene, here named sicX, is the highest of the P.aeruginosa genes expressed in human chronic wound and cystic fibrosis infections, but it is expressed at extremely low levels during standard laboratory growth. We show that sicX encodes a small RNA that is strongly induced by low-oxygen conditions and post-transcriptionally regulates anaerobic ubiquinone biosynthesis. Deletion of sicX causes P.aeruginosa to switch from a chronic to an acute lifestyle in multiple mammalian models of infection. Notably, sicX is also a biomarker for this chronic-to-acute transition, as it is the most downregulated gene when a chronic infection is dispersed to cause acute septicaemia. This work solves a decades-old question regarding the molecular basis underlying the chronic-to-acute switch in P.aeruginosa and suggests oxygen as a primary environmental driver of acute lethality.

DOI: 10.1038/s41586-023-06111-7

Source: https://www.nature.com/articles/s41586-023-06111-7

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/
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