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Mimicking the Function of Signaling Proteins: Toward Artificial Signal Transduction Therapy
Published on: September 29, 2016
Diffusible signal factor signaling regulates multiple functions in the opportunistic pathogen Stenotrophomonas
1Wellcome Wolfson Institute for Experimental Medicine, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK. s.an@qub.ac.uk.
Objective:
Stenotrophomonas maltophilia is a Gram-negative bacterium commonly isolated from nosocomial infections. Analysis of the genome of the clinical S. maltophilia isolate K279a indicates that it encodes a diffusible signal factor (DSF)-dependent cell-cell signaling mechanism that is highly similar to the system previously described in phytopathogens from the genera Xanthomonas and Xylella. Our objective was to study the function of DSF signaling in the clinical strain S. maltophilia K279a using genetic and functional genomic analyses.
Results:
We compared the wild-type strain with a mutant deficient in the rpfF (regulation of pathogenicity factors) gene that is essential for the synthesis of DSF. The effects of disruption of DSF signaling were pleiotropic with an impact on virulence, biofilm formation and pathogenesis. The phenotypic effects of rpfF mutation in S. maltophilia could be reversed by addition of exogenous DSF. Taken together, we demonstrate that DSF signaling regulates factors contributing to virulence, biofilm formation and motility of this important opportunistic pathogen.
Insights
Stenotrophomonas maltophilia uses diffusible signal factor (DSF) signaling to regulate virulence and biofilm formation. Disrupting DSF synthesis impacts multiple bacterial functions, highlighting its role in opportunistic infections.
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Molecular Biology
Background:
- Stenotrophomonas maltophilia is a significant cause of hospital-acquired infections.
- Genomic analysis reveals a diffusible signal factor (DSF)-dependent cell-cell signaling system in S. maltophilia K279a, similar to that in plant pathogens.
- Understanding DSF signaling is crucial for combating S. maltophilia infections.
Purpose of the Study:
- To investigate the functional role of DSF-dependent cell-cell signaling in the clinical isolate S. maltophilia K279a.
- To utilize genetic and functional genomic approaches to elucidate DSF signaling pathways.
- To determine the impact of DSF signaling on bacterial virulence and pathogenesis.
Main Methods:
- Comparative analysis of wild-type S. maltophilia K279a and a mutant deficient in the rpfF gene (essential for DSF synthesis).
- Genetic manipulation to create and characterize the rpfF mutant.
- Functional assays to assess virulence, biofilm formation, and motility.
Main Results:
- Disruption of DSF signaling via rpfF mutation led to pleiotropic effects on bacterial phenotype.
- Key virulence factors, biofilm formation, and motility were significantly impacted by the loss of DSF signaling.
- The observed phenotypic changes in the rpfF mutant were reversible upon the addition of exogenous DSF.
Conclusions:
- DSF-dependent cell-cell signaling is a critical regulatory mechanism in S. maltophilia K279a.
- DSF signaling influences multiple aspects of bacterial behavior, including virulence and biofilm development.
- Targeting DSF signaling pathways presents a potential strategy for controlling S. maltophilia infections.
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