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A Comparative Approach to Characterize the Landscape of Host-Pathogen Protein-Protein Interactions
Published on: July 18, 2013
Informing plasmid compatibility with bacterial hosts using protein-protein interaction data
Tim Downing1, Min Jie Lee2, Conor Archbold2
1School of Biotechnology, Dublin City University, Dublin, Ireland; The Pirbright Institute, UK.
Abstract:
The compatibility of plasmids with new host cells is significant given their role in spreading antimicrobial resistance (AMR) and virulence factor genes. Evaluating this using in vitro screening is laborious and can be informed by computational analyses of plasmid-host compatibility through rates of protein-protein interactions (PPIs) between plasmid and host cell proteins. We identified large excesses of such PPIs in eight important plasmids, including pOXA-48, using most known bacteria (n = 4363). 23 species had high rates of interactions with four blaOXA-48-positive plasmids. We also identified 48 species with high interaction rates with plasmids common in Escherichia coli. We found a strong association between one plasmid and the fimbrial adhesin operon pil, which could enhance host cell adhesion in aqueous environments. An excess rate of PPIs could be a sign of host-plasmid compatibility, which is important for AMR control given that plasmids like pOXA-48 move between species with ease.
Insights
Computational analysis of protein interactions predicts plasmid-host compatibility, aiding antimicrobial resistance (AMR) control. High interaction rates suggest successful plasmid integration, crucial for understanding AMR spread.
Area of Science:
- Microbiology
- Computational Biology
- Genetics
Background:
- Plasmids are key vectors for antimicrobial resistance (AMR) and virulence genes.
- In vitro screening for plasmid-host compatibility is time-consuming.
- Computational methods can predict plasmid-host interactions.
Purpose of the Study:
- To computationally analyze protein-protein interactions (PPIs) for predicting plasmid-host compatibility.
- To identify potential host cells compatible with significant AMR-carrying plasmids like pOXA-48.
- To understand the role of PPIs in plasmid establishment and AMR dissemination.
Main Methods:
- Analysis of protein-protein interactions (PPIs) between plasmid and host cell proteins.
- Screening of large bacterial datasets (n=4363) for interaction patterns.
- Identification of specific plasmid-host interactions, including those with pOXA-48 and plasmids common in Escherichia coli.
Main Results:
- Identified significant excesses of PPIs for eight key plasmids, including pOXA-48, across numerous bacterial species.
- Found 23 species with high interaction rates for four blaOXA-48-positive plasmids.
- Discovered 48 species with high interaction rates for plasmids prevalent in Escherichia coli, and a link between a plasmid and the pil operon enhancing adhesion.
Conclusions:
- Excessive PPIs indicate potential host-plasmid compatibility, a critical factor in AMR spread.
- Computational PPI analysis offers a scalable approach to predict plasmid-host compatibility.
- Understanding these interactions is vital for developing strategies to control AMR.
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