Towards solving the conundrum of plasmid mobility: networks of functional dependencies shape plasmid transfer

Abstract

Plasmids are key drivers of bacterial evolution by transferring genes between cells via conjugation. Yet, half of the plasmids lack all protein coding genes for this process. We searched to solve this conundrum by identifying conjugative origins of transfer over thousands of plasmids and chromosomes of Escherichia coli and Staphylococcus aureus. We found that plasmids carrying these sequences are very abundant and have the highest densities of antimicrobial resistance genes. They are hyper-parasites that directly hijack conjugative or mobilizable elements, but not both. These functional dependencies explain the co-occurrence of each type of plasmid in cells and illuminate the evolutionary relationships between the elements. We characterized systematically the genetic traits of plasmids in relation to conjugation and alternative mechanisms of transfer, and can now propose a confident putative mechanism of transfer for ca. 90% of them. The few exceptions could be passively mobilized by other processes. We conclude there is no conundrum concerning plasmid mobility.

Phylogenomics of globally spread Clonal Groups 14 and 15 of Klebsiella pneumoniae

“…The high occurrence of non-conjugative/non-mobilizable plasmids is not surprising (50), and implies either the high recombination of the mobile genetic elements in high-risk clones, with frequent deletion and acquisition events and/or the need of helper entities (e.g. conjugative plasmids, ICEs) for their mobilisation (53–55). Carriage of genes encoding adaptive functions (antimicrobial resistance, metal tolerance, thermoresistance, amongst others) reflects a history of exposure to disparate selection pressures (54).…”

“…It is also of note the high heterogeneity of small plasmids (essentially ColE1-type) long evolving in Enterobacterales, some of them particularly abundant and linked to CG15 (ColpVC, ColRNAI_rep1987). Col plasmids have been implicated in extraintestinal virulence and/or gastrointestinal colonisation in E. coli (53, 58). Their occurrence in Kp and their function are largely unknown but they contribute to the dissemination of antimicrobial resistance determinants and other host adaptive factors (cell metabolism, virulence, defence from phages or heavy metal resistance) as well as to plasmidome plasticity and evolution through events mediated by common transposases ( IS26, IS4321 , Tn 3 -like) (21, 53, 59, 60)(this study).…”

The Plasmidomic Landscape of Clinical Methicillin-Resistant Staphylococcus aureus Isolates from Malaysia

“…Besides replicon classification, staphylococcal plasmids can also be classified according to their potential for horizontal transfer, i.e., self-transmissible (conjugative), mobilizable, and non-mobilizable plasmids [ 28 , 29 , 70 ]. Staphylococcal plasmids exhibit several mobility mechanisms that may facilitate their dissemination, and these were identified from the sequences of the Malaysian MRSA plasmids as described below and summarized in Figure 4 .…”

Segregational instability of multicopy plasmids: A population genetics approach

“…In particular, we considered a small multicopy plasmid that lacks an active partitioning mechanism and therefore segregates randomly upon cell division. Multicopy plasmids are prevalent in clinical bacteria and usually carry antimicrobial resistance genes that can be transferred between neighboring bacterial cells (Ares‐Arroyo et al, 2022 ), as well as other evolutionary benefits that go well beyond horizontal transfer (Rodríguez‐Beltrán et al, 2021 ). For instance, as multicopy plasmids are present in numerous copies per cell, the mutational supply increases proportionately and, once a beneficial mutation appears, its frequency can be amplified during plasmid replication.…”