4.6 Article

Two-Component Signaling Systems Regulate Diverse Virulence-Associated Traits in Pseudomonas aeruginosa

Journal

APPLIED AND ENVIRONMENTAL MICROBIOLOGY
Volume 87, Issue 11, Pages -

Publisher

AMER SOC MICROBIOLOGY
DOI: 10.1128/AEM.03089-20

Keywords

two-component signaling systems; histidine kinase; virulence; Pseudomonas aeruginosa; signal transduction

Funding

  1. NIBIB/NIH [R01-EB017755]
  2. National Science Foundation [PHY-1454673]
  3. U.S. Army Research Office [W911NF-19-2-0026]
  4. NSF Graduate Research Fellowship Program [1745302]
  5. NIH [R01 GM082899]

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Pseudomonas aeruginosa harbors over 60 two-component signaling systems that play a role in pathogenesis, with individual genes controlling multiple virulence traits. Deletion strains lacking histidine kinases were used to confirm functions and uncover new roles in controlling virulence-associated traits, providing insight into the functions of these signaling proteins and offering a resource for future studies.
Pseudomonas aeruginosa is an opportunistic pathogen that can cause problematic infections at different sites throughout the human body. P. aeruginosa encodes a large suite of over 60 two-component signaling systems that enable cells to rapidly sense and respond to external signals. Previous work has shown that some of these sensory systems contribute to P. aeruginosa pathogenesis, but the virulence-associated processes and phenotypic traits that each of these systems controls are still largely unclear. To aid investigations of these sensory systems, we have generated deletion strains for each of 64 genes encoding histidine kinases and one histidine phosphotransferase in P. aeruginosa PA14. We carried out initial phenotypic characterizations of this collection by assaying these mutants for over a dozen virulence-associated traits, and we found that each of these phenotypes is regulated by multiple sensory systems. Our work highlights the usefulness of this collection for further studies of P. aeruginosa two-component signaling systems and provides insight into how these systems may contribute to P. aeruginosa infection. IMPORTANCE Pseudomonas aeruginosa can grow and survive under a wide range of conditions, including as a human pathogen. As such, P. aeruginosa must be able to sense and respond to diverse signals and cues in its environment. This sensory capability is endowed in part by the hundreds of two-component signaling proteins encoded in the P. aeruginosa genome, but the precise roles of each remain poorly defined. To facilitate systematic study of the signaling repertoire of P. aeruginosa PA14, we generated a library of deletion strains, each lacking one of the 64 histidine kinases. By subjecting these strains to a battery of phenotypic assays, we confirmed the functions of many and unveiled roles for dozens of previously uncharacterized histidine kinases in controlling various traits, many of which are associated with P. aeruginosa virulence. Thus, this work provides new insight into the functions of two-component signaling proteins and provides a resource for future investigations.

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