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<p><i>Pseudomonas aeruginosa</i>, a versatile Gram-negative opportunistic pathogen, relies on multiple virulence mechanisms, including a Type III Secretion System (T3SS) and several Type VI Secretion Systems (T6SS), to establish infections. The bacterial universal second messenger cyclic di-guanylate (c-di-GMP) orchestrates the lifestyle transitions of <i>Pseudomonas aeruginosa</i> between motile and biofilm-associated states and influences the expression of virulence traits. While it is clear that these systems are interconnected, their precise interaction on the single-cell level has remained unclear. In this study, we use single-cell analysis to dissect the role of c-di-GMP in the heterogeneity of virulence factors in <i>P. aeruginosa</i> populations. Our results confirm earlier findings that on the population level, high c-di-GMP levels lead to increased formation and activity of the H1-T6SS, while negatively influencing formation and activity of the T3SS. On the single-cell level, we further characterize the virulence crosstalk within <i>P. aeruginosa</i> populations by presenting a cooperative relationship among T3SS and flagellum and antagonistic relationships between presence of the H1-T6SS and the T3SS as well as the flagellum. Overall, this c-di-GMP-orchestrated heterogeneity and crosstalk of virulence systems suggest a strategy to optimize survival and pathogenicity under varying environmental conditions in the framework of the motile-sessile lifestyle transition.</p>

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Coordination of virulence factors and lifestyle transition in Pseudomonas aeruginosa through single-cell analysis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月16日

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  • Haozhe Chen,
  • Gabriele Malengo,
  • Liyun Wang,
  • Olga Vogler,
  • Mandy Renner,
  • Timo Glatter,
  • Nicole Paczia,
  • Daniel Unterweger,
  • Victor Sourjik,
  • Andreas Diepold

摘要

Pseudomonas aeruginosa, a versatile Gram-negative opportunistic pathogen, relies on multiple virulence mechanisms, including a Type III Secretion System (T3SS) and several Type VI Secretion Systems (T6SS), to establish infections. The bacterial universal second messenger cyclic di-guanylate (c-di-GMP) orchestrates the lifestyle transitions of Pseudomonas aeruginosa between motile and biofilm-associated states and influences the expression of virulence traits. While it is clear that these systems are interconnected, their precise interaction on the single-cell level has remained unclear. In this study, we use single-cell analysis to dissect the role of c-di-GMP in the heterogeneity of virulence factors in P. aeruginosa populations. Our results confirm earlier findings that on the population level, high c-di-GMP levels lead to increased formation and activity of the H1-T6SS, while negatively influencing formation and activity of the T3SS. On the single-cell level, we further characterize the virulence crosstalk within P. aeruginosa populations by presenting a cooperative relationship among T3SS and flagellum and antagonistic relationships between presence of the H1-T6SS and the T3SS as well as the flagellum. Overall, this c-di-GMP-orchestrated heterogeneity and crosstalk of virulence systems suggest a strategy to optimize survival and pathogenicity under varying environmental conditions in the framework of the motile-sessile lifestyle transition.