Interaction of F Plasmids could minimise spread of AMR genes in bacterial infections

Horizontal gene transfer via conjugation plays an extremely important role in bacterial evolution. Bacterial conjugation was first described by Lederberg and Tatum in the 1940s following the discovery of the F plasmid, which is also known as the fertility (F) factor. When bacteria join together, a plasmid is transferred from donor to recipient bacteria, moving in a single direction.

In F-like plasmids, efficient DNA transfer is mediated by close association between donor and recipient bacteria. Examples of F-like plasmids can be found in Salmonella enterica, E. coli and Klebsiella pneumoniae . This process, known as mating pair stabilization (MPS), is mediated by interactions between the plasmid-encoded outer membrane (OM) protein TraN in the donor and chromosomally-encoded OM proteins in the recipient.

Researchers from Research Complex at Harwell (Dr Konstantinos Beis and Chloe Seddon) and Imperial College London (Professor Frankel and Dr Low) have worked together to continue their research on the existence of seven TraN sequence types, which are grouped into four structural types they named - TraNα, TraNβ, TraNγ, TraNδ. During their previous study, their research revealed specific pairing between many of these structural types. While the focus of conjugation studies over the last decades has been on the donor, it has become apparent that rather than being a bystander, the recipient plays a major role in MPS formation and efficient DNA transfer. Recipients cannot avoid conjugation. MPS, while playing a role in increasing conjugation efficiency, is not essential for transfer to occur.

In a new paper published in the Journal of Bacteriology, the team have found that although structurally similar, TraNα, when encoded by the Salmonella enterica pSLT plasmid (TraNα2), binds to the outer membrane porin OmpW in both E. coli and Citrobacter rodentium, while when TraNα is encoded by the R100-1 plasmid (TraNα1), it only binds OmpW of E. coli. Predictions suggested that this specificity is mediated by a single amino acid difference. Moreover, it was revealed that single amino acids insertions into loop 3 of OmpK36 affect the conjugation efficiency of the Klebsiella pneumoniae resistance plasmid pKpQIL.

The understanding of MPS not only explains conjugation specificity, but it could have important applications to clinical medicine, as it could enable the design of conjugation inhibitors that would minimise the spread of antimicrobial-resistant (AMR) genes and development of conjugation based plasmid delivery into specific recipients.


The Interaction of the F-Like Plasmid-Encoded TraN Isoforms with Their Cognate Outer Membrane Receptors, W.W. Low, C. Seddon, K. Beis and G. Frankel, Journal of Bacteriology, 205, 4 (2023)