Biology subjects

de Quinto, I.

Publications and source records attributed to de Quinto, I..

3 recordsLinked to original sources

bioRxiv2026

Multireplicon plasmids emerge under predictable rules and drive the spread of antimicrobial resistance across bacterial hosts

Plasmids are DNA molecules that replicate independently of the bacterial chromosome and are typically associated with the spread of antimicrobial resistance (AMR) and virulence determinants, among other relevant traits. Fusion events between plasmids generate larger, complex backbones that carry two or more replication systems, known as multireplicon plasmids. Despite decades of study, we are still far from understanding how multireplicon plasmids arise, persist, and shape the evolution of AMR. Here, we analyzed 24,000 non-redundant plasmids across bacterial genera and found that more than 30% of them encoded multiple replicons. Compared to single-replicon plasmids, multireplicon plasmids were larger, were enriched in genes encoding antimicrobial, metal, and biocide resistance as well as virulence factors, and showed higher mobility and a broader host range. We also found that multireplicon assembly is not random. Some replicon pairs repeatedly merge into stable multireplicon plasmids, while other pairs rarely fuse even when they commonly coexist intracellularly. We also show that replicon pairs tend to be localized either in close proximity to one another or on opposite poles of the plasmid. We further highlight that multireplicon plasmids can be broadly classified into two groups: long-term coevolving replicon pairs and transient associations that lack a shared evolutionary history. Finally, we reveal the molecular mechanisms underlying multireplicon formation and highlight the role of insertion sequences in their formation and maintenance. Together, our work sheds light on the abundance, gene content, evolutionary patterns, and formation dynamics of multireplicon plasmids and pinpoints their relevance to bacterial evolution and human health.

microbiology↗

bioRxiv2025

Plasmids promote bacterial evolution through a copy number-driven increase in mutation rate

Plasmids are autonomously replicating DNA molecules that stably coexist with chromosomes in bacterial cells. These genetic elements drive horizontal gene transfer and play a fundamental role in bacterial ecology and evolution. Theory suggests that plasmids might evolve faster than chromosomes, as the mutation rate per gene should proportionally increase with plasmid copy number. However, the segregation of plasmid copies to daughter cells is random, introducing an additional layer of genetic drift, known as segregational drift, that might delay plasmid evolution. The interplay between plasmid mutational supply and segregational drift determines the evolutionary rate of plasmid-encoded genes, yet the relative contribution of these opposite forces in plasmid evolution remains unclear. Here, we took a classical population genetics framework to devise a mathematical approximation that predicts the fate of plasmid mutations in bacterial populations. We then validate these predictions by integrating computational, experimental, and bioinformatic approaches. Our findings show that plasmid mutation rates scale logarithmically with copy number: while increasing copy number elevates the mutation rate, the effect diminishes at higher copy numbers, where additional copies yield only marginal increases. Nonetheless, the supply of new mutations consistently surpasses the impact of segregational drift across all copy number levels. These results underscore plasmids as powerful platforms for bacterial evolvability and help explain their remarkable prevalence across microbial phylogeny.

microbiology↗

bioRxiv2024

Universal rules govern plasmid copy number

Plasmids -autonomously replicating DNA molecules- exhibit a broad range of replication and mobility strategies, genetic repertoires, host ranges, sizes, and copies per cell. However, the determinants of plasmid copy number (PCN) remain poorly understood. Here, we use extensive DNA sequencing data to analyse the copy number of thousands of diverse bacterial plasmids in a comprehensive manner. We find that PCN is highly variable, spanning nearly three orders of magnitude, and that it is intrinsically robust against changes in genomic context. We further show that PCN variability is tightly associated with plasmid lifestyles, and propose the concept of replicon dominance to explain interactions in widespread multi-replicon plasmids. Finally, we uncover a universal scaling law that links copy number and plasmid size across bacterial species, indicating that pervasive constraints modulate the PCN-size trade-off.

microbiology↗