The extended mobility of plasmids

Abstract

Plasmids play key roles in the spreading of many traits, ranging from antibiotic resistance to varied secondary metabolism, from virulence to mutualistic interactions, and from defense to antidefense. Our understanding of plasmid mobility has progressed extensively in the last few decades. Conjugative plasmids are still often the textbook image of plasmids, yet they are now known to represent a minority. Many plasmids are mobilized by other mobile genetic elements, some are mobilized as phages, and others use atypical mechanisms of transfer. This review focuses on recent advances in our understanding of plasmid mobility, from the molecular mechanisms allowing transfer and evolutionary changes of plasmids to the ecological determinants of their spread. In this emerging, extended view of plasmid mobility, interactions between mobile genetic elements, whether involving exploitation, competition, or elimination, affect plasmid transfer and stability. Likewise, interactions between multiple cells and their plasmids shape the latter patterns of transfer through transfer-mediated bacterial predation, interference, or eavesdropping in cell communication, and by deploying defense and antidefense activity. All these processes are relevant for microbiome intervention strategies, from plasmid containment in clinical settings to harnessing plasmids in ecological or industrial interventions.

Graphical Abstract

Figure 1.

Plasmid distribution in the RefSeq database. The NCBI RefSeq database (release 229, 3 March 2025) includes 47 368 complete bacterial genome sequences, of which 21 801, distributed across 28 phyla, contain a total of 58 156 plasmids (A). For the 10 bacterial phyla with the highest number of plasmid-containing members, the abundance of genomes with and without plasmids is shown (B). The number of plasmids per bacterial host ranges from 0 to 28 and decreases exponentially (C). Plasmid size exhibits a bimodal distribution (when log-transformed) (D).

Figure 2.

Association between relaxase MOB classes and MPF systems. Left panel: The schematic phylogenetic tree illustrates the evolutionary relationships between MPF types based on the VirB4 phylogeny, highlighting their diversification within diderms and subsequent transfer to monoderms. Examples of conjugative systems representing each MPF type are displayed at the right. The phylogenetic tree was adapted from [58]. Right panel: The chord diagram displays a ring featuring the nine relaxase MOB classes and eight MPF types. The width of each sector corresponds to the abundance of MOB or MPF in an NCBI dataset of 12 148 plasmids. Links indicate co-occurrence of MOB and MPF within the same plasmid. The data were taken from Supplementary Table S1 of [27].

Figure 3.

(A) Mechanism of mobility of phage-plasmids. (B) Distribution of plasmids per type in Bacteria and in E. coli (as described in [102]): conjugative (pCONJ), mobilizable with a relaxase (pMOB), mobilizable having an oriT (pOriT, only represented for E. coli), and phage-plasmid. “?” represents other, mostly uncharacterized, plasmids. Frequency of each type among all plasmids is proportional to the surface of the rectangle. (C) Comparison of plasmid mobility by conjugation (left) or within phage particles (right). P-Ps can produce very large progeny, but at the cost of cell death. Conjugative plasmids usually have broader host ranges than temperate phages and are more tolerant to extensive gene gain or loss. P-Ps may disperse faster, especially in aquatic environments, since their transfer does not require cell-to-cell contact.

Figure 4.

Mechanisms allowing the mobility of plasmids that do not encode a complete machinery for self-transfer. Mechanisms of transfer may involve mobilization by a conjugative element (top three rows) where a hitcher plasmid recruits an MPF and eventually also a relaxase from other plasmids. Phages may transfer plasmids by transduction either because they make generalized transduction and randomly package bacterial DNA in some of their capsids or because plasmids have evolved sequences to favor recognition by the phage packaging system. Plasmids may also transfer by other processes such as conduction (co-integration in a transferable plasmid), natural transformation, or within vesicles (although the latter mechanism is yet poorly understood).

Figure 5.

Interacting partners that promote targeted conjugation. The left part of the panels represents conditions where conjugation is promoted, while the right part includes scenarios where conjugation is impeded. The upper panel shows the interaction between TraN and a specific Omp versus nonspecific partner. The middle panel depicts the interaction of a specific PilV adhesin with a compatible LPS versus an incompatible LPS. The lower panel illustrates the plasmid transfer to an empty recipient versus a recipient already containing a copy of the plasmid.

Figure 6.

Antiplasmid defense systems and plasmid antidefense systems. The first panel illustrates the action of plasmid-encoded methylases (left) and antirestriction proteins (right) in protecting the transferred DNA from the restriction activity of R–M systems in the recipient cell. The second panel depicts the antiplasmid immunity activity of CRISPR-Cas systems (left) and the antidefense activity of Acr proteins (right). The third panel shows the defense systems pAgo/DmdDE and DmdABC (Lamassu) (left) and the fertility inhibition activity exerted by a plasmid against the transfer of a co-resident plasmid (right). The fourth panel represents the counterattack deployed by T6SS against bacteria harboring conjugative plasmids (left) and the repression of chromosome-encoded T6SS by a transcription factor encoded in the conjugative plasmid (right).

Figure 7.

Key mechanisms of genetic change in plasmids (top panel) and transitions in terms of mobility for plasmids mobilizable by conjugation (lower panel). Plasmids genomes may change by several mechanisms (top), including fusions and fissions of plasmids, recombination, translocation of transposable elements and mutations and deletions of genetic material. Successions of gene gains and losses may result in transitions between types of mobility (lower panel). Those resulting in more limited mobility are more frequent because they only require gene deletions, but available evidence suggests they are counter-selected [27].