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Host-Pathogen Interactions: What the EHEC Are We Learning from Host Genome-Wide Screens?
Jason P Lynch1,2,3, Cammie F Lesser4,2,3
1Department of Medicine, Division of Infectious Diseases, Massachusetts General Hospital, Cambridge, Massachusetts, USA.
Abstract:
Several genome-wide screens have been conducted to identify host cell factors involved in the pathogenesis of bacterial pathogens whose virulence is dependent on type III secretion systems (T3SSs), nanomachines responsible for the translocation of proteins into host cells. In the most recent of these, Pacheco et al. (mBio 9:e01003-18, 2018, http://mbio.asm.org/content/9/3/e01003-18.full) screened a genome-wide CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats with Cas9) knockout library for host proteins involved in the pathogenesis of enterohemorrhagic Escherichia coli (EHEC). Their study revealed an unrecognized link between EHEC's two major virulence determinants (its T3SS and Shiga toxins). We discuss these findings in light of data from three other genome-wide screens. Each of these studies uncovered multiple host cell determinants, which curiously share little to no overlap but primarily are involved in mediating early interactions between T3SSs and host cells. We therefore consider how each screen was performed, the advantages and disadvantages of each, and how follow-up studies might be designed to address these issues.
Insights
Genome-wide screens identified host factors crucial for bacterial pathogenesis. A new study reveals a link between enterohemorrhagic Escherichia coli
Area of Science:
- Microbiology
- Genetics
- Molecular Biology
Background:
- Type III secretion systems (T3SSs) are essential bacterial virulence factors.
- Genome-wide screens identify host factors in bacterial pathogenesis.
Purpose of the Study:
- To identify host cell factors involved in enterohemorrhagic E. coli (EHEC) pathogenesis.
- To investigate the link between EHEC's T3SS and Shiga toxins.
Main Methods:
- Genome-wide CRISPR/Cas9 knockout library screening.
- Analysis of host proteins mediating bacterial-host interactions.
Main Results:
- A novel connection between EHEC's T3SS and Shiga toxins was discovered.
- Multiple host cell determinants were identified, primarily involved in early T3SS-host interactions.
- Limited overlap was observed between different genome-wide screening approaches.
Conclusions:
- Host cell factors play a critical role in EHEC pathogenesis.
- Further research is needed to understand the discrepancies between screening methods and optimize follow-up studies.
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