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Automated Separation of C. elegans Variably Colonized by a Bacterial Pathogen
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Diverse gut pathogens exploit the host engulfment pathway via a conserved mechanism
Mahitha Shree Anandachar1, Suchismita Roy2, Saptarshi Sinha2
1Department of Cellular and Molecular Medicine, University of California San Diego, San Diego, California, USA; Department of Pathology, University of California San Diego, San Diego, California, USA.
The Journal of Biological Chemistry
|October 27, 2023
Summary
Pathogens use effector proteins to evade host defenses. Researchers identified a key host protein interaction site targeted by these effectors, revealing a vulnerability that could be exploited for new therapies.
Area of Science:
- Cellular microbiology
- Host-pathogen interactions
- Molecular immunology
Background:
- Macrophages engulf pathogens in phagolysosomes, a crucial defense mechanism.
- Pathogens employ effector proteins with WxxxE motifs to disrupt host cell functions and establish intracellular niches.
- Understanding these molecular interactions is key to combating infectious diseases.
Purpose of the Study:
- To identify the host protein targeted by pathogen WxxxE effectors.
- To elucidate the molecular mechanism of effector binding to the host protein.
- To investigate the functional consequences of disrupting this interaction.
Main Methods:
- Homology modeling and site-directed mutagenesis to identify the binding site.
- Protein-protein interaction network analysis.
- In silico network perturbation and functional assays in host cells.
Main Results:
- A conserved "hot spot" on ELMO1 (Engulfment and Cell Motility protein 1) PH domain binds diverse WxxxE effectors.
- A lysine triad on ELMO1 directly interacts with SifA, IpgB1, IpgB2, and Map.
- Disrupting SifA-ELMO1 interaction reduces Rac1 activity and microbial invasion.
Conclusions:
- The ELMO1-effector interface represents a convergence point for pathogen subversion strategies.
- This interface is a critical site of coevolved molecular adaptations between pathogens and hosts.
- Targeting this interface offers a potential therapeutic strategy against various bacterial infections.
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