The ability to switch between different lifestyles allows bacterial pathogens to thrive in diverse ecological niches^1,2. 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.

在不同生活方式之间转换的能力允许细菌病原体在不同的生态位^1,2中茁壮成长。然而，缺乏对其在人类宿主内生活方式变化的分子理解。在这里，通过直接检查人源样本中的细菌基因表达，我们发现了一种基因，它可以协调机会性病原体铜绿假单胞菌的慢性和急性感染之间的转变。该基因（此处命名为sicX）的表达水平是人类慢性伤口和囊性纤维化感染中表达水平最高的铜绿 假单胞菌基因，但在标准实验室生长期间其表达水平极低。我们证明sicX编码一种由低氧条件强烈诱导并转录后调节厌氧泛醌生物合成的小 RNA。在多种哺乳动物感染模型中，删除sicX会导致铜绿 假单胞菌从慢性生活方式转变为急性生活方式。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导致急性败血症时，它是下调最多的基因。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变的分子基础的问题，并表明氧气是急性致死性的主要环境驱动因素。