A Pseudomonas aeruginosa small RNA regulates chronic and acute infection

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.

Automated summary

The ability of bacterial pathogens to switch between different lifestyles is essential for their survival in diverse ecological niches. In this study, researchers discover a gene, sicX, that regulates the transition between chronic and acute infection in the opportunistic pathogen Pseudomonas aeruginosa. Expression of sicX is highest in human chronic wound and cystic fibrosis infections, but low during standard laboratory growth. The study reveals that sicX encodes a small RNA that is induced by low-oxygen conditions and regulates anaerobic ubiquinone biosynthesis, leading to the switch from chronic to acute lifestyle in P. aeruginosa.