Journal article
Global Regulatory Pathways Converge To Control Expression of Pseudomonas aeruginosa Type IV Pili
mBio, Vol.13(1), pp.e0369621-e0369621
01/25/2022
DOI: 10.1128/MBIO.03696-21
PMCID: PMC8787478
PMID: 35073734
Abstract
The opportunistic pathogen Pseudomonas aeruginosa relies upon type IV pili (Tfp) for host colonization and virulence. Tfp are retractile surface appendages that promote adherence to host tissue and mediate twitching motility, a form of surface-associated translocation. Tfp are composed of a major structural pilin protein (PilA), several less abundant, fiber-associated pilin-like proteins (FimU, PilV, PilW, PilX, and PilE), and a pilus-associated tip adhesin and surface sensor (PilY1). Several proteins critical for Tfp biogenesis and surface sensing are encoded by the
operon. Tfp biogenesis is regulated by the global transcription factor Vfr and its allosteric effector, cyclic AMP (cAMP). Our investigation into the basis for reduced Tfp production in cAMP/
mutants revealed a defect in the expression of the
operon. We found that cAMP/Vfr activation of the
operon occurs via direct binding of Vfr to a specific
promoter sequence. We also refined the role of the AlgZ/AlgR two-component system in
regulation by demonstrating that phosphorylation of the response regulator AlgR is required for maximal binding to the
promoter region
. Vfr also regulates expression of the
operon, revealing an indirect regulatory loop affecting
operon transcription. Overall, these results demonstrate that two linked but independent regulatory systems couple the expression of Tfp biogenesis and surface sensing genes and highlight the regulatory complexity governing expression of P. aeruginosa virulence factors.
Pseudomonas aeruginosa is an opportunistic pathogen responsible for a wide range of infections. An extensive repertoire of virulence factors aid in P. aeruginosa pathogenesis. Type IV pili (Tfp) play a critical role in host colonization and infection by promoting adherence to host tissue, facilitating twitching motility and mediating surface-associated behaviors. The
operon encodes several pilus-associated proteins that are essential for proper Tfp function and surface sensing. In this study, we report that linked but independent regulatory systems dictate Tfp biogenesis. We also demonstrated the importance of different phosphorylation states of the AlgZ/AlgR two-component system and its role in Tfp biogenesis. Overall, this study furthers our understanding of the complex regulatory mechanisms that govern the production of a critical and multifaceted virulence factor.
Details
- Title: Subtitle
- Global Regulatory Pathways Converge To Control Expression of Pseudomonas aeruginosa Type IV Pili
- Creators
- Kimberly A Coggan - University of North Carolina at Chapel HillMatthew G Higgs - University of North Carolina at Chapel HillEvan D Brutinel - University of IowaJeremiah N Marden - University of North Carolina at Chapel HillPeter J Intile - University of IowaHanne C Winther-Larsen - University of OsloMichael Koomey - University of OsloTimothy L Yahr - University of IowaMatthew C Wolfgang - University of North Carolina at Chapel Hill
- Resource Type
- Journal article
- Publication Details
- mBio, Vol.13(1), pp.e0369621-e0369621
- DOI
- 10.1128/MBIO.03696-21
- PMID
- 35073734
- PMCID
- PMC8787478
- NLM abbreviation
- mBio
- ISSN
- 2161-2129
- eISSN
- 2150-7511
- Grant note
- R56 AI055042 / NIAID NIH HHS R01 AI055042 / NIAID NIH HHS R01 AI097264 / NIAID NIH HHS R01 AI069116 / NIAID NIH HHS
- Language
- English
- Date published
- 01/25/2022
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984297434802771
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