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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.

This Review highlights how we can build upon the relatively new and rapidly developing field of research into bacterial quorum sensing (QS). We now have a depth of knowledge about how bacteria use QS signals to communicate with each other and to coordinate their activities. In recent years there have been extraordinary advances in our understanding of the genetics, genomics, biochemistry, and signal diversity of QS. We are beginning to understand the connections between QS and bacterial sociality. This foundation places us at the beginning of a new era in which researchers will be able to work towards new medicines to treat devastating infectious diseases, and use bacteria to understand the biology of sociality.

This review highlights how we can build upon the relatively new and rapidly developing field of bacterial communication or quorum sensing (QS). We now have a depth of knowledge about how bacteria use QS signals to communicate with each other and coordinate activities. There have been extraordinary advances in QS genetics, genomics, biochemistry, and diversity of signaling systems. We are beginning to understand the connections between QS and bacterial sociality. This foundation places us at the precipice of a new era where researchers can advance towards development of new medicines to treat devastating infectious diseases, and in parallel use bacteria to understand the biology of sociality.

Bacteria often adopt a sessile biofilm lifestyle that is resistant to antimicrobial treatment. Opportunistic pathogenic bacteria like Pseudomonas aeruginosa can develop persistent infections. To gain insights into the differences between free-living P. aeruginosa cells and those in biofilms, and into the mechanisms underlying the resistance of biofilms to antibiotics, we used DNA microarrays. Here we show that, despite the striking differences in lifestyles, only about 1% of genes showed differential expression in the two growth modes; about 0.5% of genes were activated and about 0.5% were repressed in biofilms. Some of the regulated genes are known to affect antibiotic sensitivity of free-living P. aeruginosa. Exposure of biofilms to high levels of the antibiotic tobramycin caused differential expression of 20 genes. We propose that this response is critical for the development of biofilm resistance to tobramycin. Our results show that gene expression in biofilm cells is similar to that in free-living cells but there are a small number of significant differences. Our identification of biofilm-regulated genes points to mechanisms of biofilm resistance to antibiotics.

Bacteria exhibit many social activities which are coordinated by complex inter-species cell–cell signalling (quorum sensing) systems, but the way that quorum sensing mediates social behaviour is incompletely understood. Experiments with the pathogen Pseudomonas aeruginosa now show that an important cell–cell signal is packaged into outer membrane vesicles, and that these vesicles are critical for communication and group behaviour. Intriguingly, the signal molecule mediates its own packaging into these vesicles. Vesicle-mediated trafficking is common in eukaryotes, but this is the first report of membrane vesicles as mediators of communication in a prokaryote. Many bacteria use extracellular signals to communicate and coordinate social activities, a process referred to as quorum sensing1. Many quorum signals have significant hydrophobic character, and how these signals are trafficked between bacteria within a population is not understood. Here we show that the opportunistic human pathogen Pseudomonas aeruginosa packages the signalling molecule 2-heptyl-3-hydroxy-4-quinolone (pseudomonas quinolone signal; PQS)2 into membrane vesicles that serve to traffic this molecule within a population. Removal of these vesicles from the bacterial population halts cell–cell communication and inhibits PQS-controlled group behaviour. We also show that PQS actively mediates its own packaging and the packaging of other antimicrobial quinolines produced by P. aeruginosa into vesicles. These findings illustrate that a prokaryote possesses a signal trafficking system with features common to those used by higher organisms and outlines a novel mechanism for delivery of a signal critical for coordinating group behaviour in P. aeruginosa.