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Identification of Host Pathways Targeted by Bacterial Effector Proteins using Yeast Toxicity and Suppressor Screens
Published on: October 25, 2019
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An unbiased method for clustering bacterial effectors using host cellular phenotypes.
Andrea J Dowling1, David J Hodgson
1Biosciences, College of Life & Environmental Sciences, University of Exeter, Cornwall Campus, Penryn, United Kingdom.
Applied and Environmental Microbiology
|December 4, 2013
Summary
We developed a new method for classifying bacterial effector proteins using cell analysis, advancing beyond visual methods. This approach predicts effector functions, aiding research on microbial pathogens like Photorhabdus asymbiotica.
Area of Science:
- Microbiology
- Cell Biology
- Genomics
Background:
- Bacterial effector proteins are crucial virulence factors.
- Identifying effector function is vital for understanding pathogenesis.
- Current methods for effector classification are often qualitative and time-consuming.
Purpose of the Study:
- To introduce a novel, unbiased high-content morphometric cell analysis method for classifying bacterial effector phenotypes.
- To demonstrate the utility of this method in predicting effector functions.
- To investigate effector functions in the pathogen Photorhabdus asymbiotica.
Main Methods:
- Unbiased high-content morphometric cell analysis.
- Statistical cluster analysis of macrophage phenotypes.
- Investigation of effector-modulated phagocytosis.
Main Results:
- Classified 23 antimacrophage effectors from Photorhabdus asymbiotica into three functional groups: adhesins, cytolethal toxins, and cytomodulating toxins.
- Demonstrated that effectors modulate phagocytosis, with the type of modulation linked to their functional cluster.
- Validated the method's ability to predict effector function.
Conclusions:
- The novel cell analysis method provides an objective and efficient way to classify bacterial effector functions.
- This approach facilitates rapid functional follow-up of candidate effectors.
- The method is broadly applicable for analyzing virulence factors across diverse microbial genomes.
