Informing plasmid compatibility with bacterial hosts using protein-protein interaction data

Abstract

The compatibility of plasmids in a new host cell is of broad significance, largely due to these plasmids' role in spreading antimicrobial resistance (AMR) and virulence factor genes. Such horizontal gene transfer can transform the host cell phenotypes, but only if the plasmid genes can be replicated, expressed and work synergistically in the new host cell. In vitro screening to evaluate this is laborious and can be informed by efficient computational analyses of plasmid-host compatibility through rates of protein-protein interactions (PPIs) between plasmid and host cell proteins. We identified instances of large excesses of such PPIs in eight plasmids of public health concern, including pOXA-48, using the PPI data of samples representative of most known bacteria (n=4,363). This identified 23 species with high rates of PPIs with four blaOXA-48-positive plasmids, such as Pseudomonas aeruginosa. This approach also identified 48 species with high compatibility with four plasmids common in Escherichia coli infections. We found a strong association of one plasmid with the fimbrial adhesin operon pil, which could enhance host cell adhesion in water environments. Our work on eight plasmids demonstrated that an excess rate of PPIs could be a sign of host-plasmid compatibility, which is important for AMR control because plasmids like pOXA-48 can jump between species with apparent ease. This compatibility could also be a sign of long-term co-evolution and therefore compensation by the host cell, implying the plasmids could be retained even in the absence of antibiotic pressure.