These paradoxical findings suggest that there may be connections between QS and other key physiological pathways that have yet to be revealed. Despite the importance of cell-cell communication for virulence ( Rumbaugh et al., 2009) and high conservation across divergent phylogenies, key QS regulators in diverse species, such as Pseudomonas aeruginosa, Vibrio cholerae, and Staphylococcus aureus, frequently lose function ( Mould and Hogan, 2021), due to recent missense and nonsense mutations, indels, or genome rearrangements. Quorum sensing (QS) is a mechanism of microbial communication that regulates the expression of a suite of genes in response to diffusible autoinducers in a population ( Schuster and Greenberg, 2007 Schuster et al., 2003).
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This insight could lead to better ways to predict the outcomes of bacterial infections and how to best treat them. Loss of functional LasR changes the way that cells use nutrients, and thus will reshape how they interact with host cells and other bacteria. This work reveals a new connection between quorum sensing genes and nutrient regulation in bacterial cells. aeruginosa switches between different nutrient sources. Further experiments narrowed down the molecular cascade required for the rise of lasR mutants, identifying a pathway that regulates how P. Differences in growth rates and ways to use resources (rather than changes in cell-to-cell interactions) best explained why lasR mutants become more successful. aeruginosa growth to understand how lasR mutant cells evolve. used laboratory evolution experiments and computer models of P.
To investigate this question, Mould et al. Why this is the case – and in fact, why genes associated with quorum sensing often lose function during infection – is still unclear. aeruginosa strains carrying a damaged version of the lasR gene are typically more ill and less likely to recover. aeruginosa with mutations that disable the quorum-sensing signal receptor LasR, a molecular actor that can switch on many other genes in a cell. This is the case for Pseudomonas aeruginosa, which normally lives in the soil but can also cause deadly conditions, especially in hospital settings. However, species of harmful bacteria often lose their quorum sensing abilities when they infect humans. For example, individuals in many bacterial species can start to work together under certain circumstances this ability is underpinned by a system called quorum sensing, which allows cells to detect nearby conspecifics. Editor's evaluationīacteria can evolve quickly, a skill that proves useful in ever-changing environments. We propose that in vivo metabolomes contribute to pathogen evolution, which may influence the progression of disease and its treatment. Our analysis of bronchoalveolar lavage fluid metabolomes identified compounds that negatively correlate with lung function, and we show that these compounds support enhanced growth of LasR – cells in a CbrB-controlled manner. LasR – lineages frequently arise in cystic fibrosis lung infections and their detection correlates with disease severity. The evolution of LasR – lineages in laboratory and clinical isolates depended on activity of the two-component system CbrAB, which modulates substrate prioritization through the catabolite repression control pathway. A model based on the intrinsic growth kinetics for a wild type strain and its LasR – derivative, in combination with an experimental evolution based genetic screen and further genetics analyses, indicated that differences in metabolism were sufficient to explain the rise of these common mutant types. While LasR contributes to virulence through its role in quorum sensing, lasR mutants have been associated with more severe disease.
Here, we show that differences in specific metabolic regulation rather than inter-strain interactions explain the frequent presence of lasR loss-of-function (LOF) mutations in the bacterial pathogen Pseudomonas aeruginosa. Microbes frequently evolve in reproducible ways.
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