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- W2023127566 abstract "<h3>Abstract</h3> <h3>Introduction</h3> <i>Pseudomonas aeruginosa</i> is an opportunistic pathogen with an extraordinary metabolic adaptability and a large repertoire of virulence factors that allow it to cause acute and chronic infections. Treatment of <i>P. aeruginosa</i> infections often fail due to its antibiotic resistance mechanisms, thus novel strategies aim at targeting virulence factors instead of growth-related features. However, there is currently not a clear understanding of the dynamic nature inherent to the wiring of its virulence networks. <h3>Results</h3> In this study, we manually reconstructed the signalling and transcriptional regulatory networks of 12 acute (incl. pyocin and elastase) and 8 chronic virulence factors (incl. biofilm), and the 4 quorum sensing (QS) systems of <i>P. aeruginosa.</i> Using Boolean modelling (BM), we unveiled the important roles that stochasticity and node connectivity play in the networks’ inherent dynamicity and robustness. We showed that both the static interactions, as well as the time when the interactions take place, are important features in the QS network. In addition, we found that the virulence factors of the acute networks are under strict repression, or under an activation that is non-strict or oscillatory, while the chronic networks favour the repression of the virulence factor, with only moderate activation under certain conditions. <h3>Conclusion</h3> In conclusion, our <i>in silico</i>-modelling framework provided us with a system-level view of the <i>P. aeruginosa</i> virulence and QS networks to gain new insights into the various mechanisms that support its pathogenicity and response to stressors targeting these networks. Thus, we suggest that BM provides an invaluable tool to guide the design of new treatments against <i>P. aeruginosa.</i>" @default.
- W2023127566 created "2016-06-24" @default.
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- W2023127566 date "1994-07-31" @default.
- W2023127566 modified "2023-09-23" @default.
- W2023127566 title "”Is Your Alpha Big Enough to Cover Its Taxes?“" @default.
- W2023127566 doi "https://doi.org/10.3905/jpm.1994.96" @default.
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