Origins of transfer establish networks of functional dependencies for plasmid transfer by conjugation

Abstract

Plasmids can be transferred between cells by conjugation, thereby driving bacterial evolution by horizontal gene transfer. Yet, we ignore the molecular mechanisms of transfer for many plasmids because they lack all protein-coding genes required for conjugation. We solved this conundrum by identifying hundreds of plasmids and chromosomes with conjugative origins of transfer in Escherichia coli and Staphylococcus aureus. These plasmids (pOriT) hijack the relaxases of conjugative or mobilizable elements, but not both. The functional dependencies between pOriT and other plasmids explain their co-occurrence: pOriT are abundant in cells with many plasmids, whereas conjugative plasmids are the most common in the others. We systematically characterized plasmid mobility in relation to conjugation and alternative mechanisms of transfer and can now propose a putative mechanism of transfer for ∼90% of them. In most cases, plasmid mobility seems to involve conjugation. Interestingly, the mechanisms of mobility are important determinants of plasmid-encoded accessory traits, since pOriTs have the highest densities of antimicrobial resistance genes, whereas plasmids lacking putative mechanisms of transfer have the lowest. We illuminate the evolutionary relationships between plasmids and suggest that many pOriT may have arisen by gene deletions in other types of plasmids. These results suggest that most plasmids can be transferred by conjugation.

Annotating Metagenomically Assembled Bacteriophage from a Unique Ecological System using Protein Structure Prediction and Structure Homology Search

“…The consistency in size distribution for most subgenomic sized ACCs across samples could either be due to a particular set of selectively advantageous genes, or even type of plasmid mobility. Previous studies that have also observed bi-modal distribution of plasmids within species observed correlations between mobility type and plasmid sizes (12). Additionally, it is possible that size constraints can result from bacteriophage transduction of plasmids which are limited by size compatibility -and similar to the observation of bacteriophage and plasmid size distributions made in the study by (12).…”

“…Previous studies that have also observed bi-modal distribution of plasmids within species observed correlations between mobility type and plasmid sizes (12). Additionally, it is possible that size constraints can result from bacteriophage transduction of plasmids which are limited by size compatibility -and similar to the observation of bacteriophage and plasmid size distributions made in the study by (12). Interestingly, the largest peak in our putative bacteriophage ACCs matches the largest of the two peaks observed for all ACCs at approximately 42 kbp.…”

A diverse repertoire of anti-defense systems is encoded in the leading region of plasmids

“…These will allow studying additional plasmids and specifically investigating early expressed genes in small plasmids encoding only an oriT . Such small plasmids are important to study, as they have been shown to carry numerous antimicrobial resistance genes (ARGs) and make up at least half of all plasmids 5,8 .…”

“…Our analyses were restricted to conjugative elements with a relaxase and a known oriT sequence, which were required to determine the transfer directionality. However, a large portion of the relaxase-containing sequences lacked a known oriT sequence, hampering our ability to comprehensively study potential conjugative elements 8,12 . Further, numerous small plasmids do not encode for relaxases and undergo transfer by exploiting the relaxosome of other conjugative elements in trans 85,6 .…”

“…Such elements, termed "mobilizable plasmids", can be transferred by exploiting the conjugation machinery of a co-residing conjugative element 6,7 . We will refer to both conjugative and mobilizable elements as "potential conjugative elements", as they all have the potential to be transferred to another cell by conjugation 8 .…”