Staphylococcal phages and pathogenicity islands drive plasmid evolution

Suzanne Humphrey,R Craig Maclean,Álvaro San Millán,Alejandra Flor-Duro,John Chen,Carles Ubeda,Macarena Toll-Riera,John Connolly,José R Penadés

doi:10.1038/s41467-021-26101-5

Abstract

Conjugation has classically been considered the main mechanism driving plasmid transfer in nature. Yet bacteria frequently carry so-called non-transmissible plasmids, raising questions about how these plasmids spread. Interestingly, the size of many mobilisable and non-transmissible plasmids coincides with the average size of phages (~40 kb) or that of a family of pathogenicity islands, the phage-inducible chromosomal islands (PICIs, ~11 kb). Here, we show that phages and PICIs from Staphylococcus aureus can mediate intra- and inter-species plasmid transfer via generalised transduction, potentially contributing to non-transmissible plasmid spread in nature. Further, staphylococcal PICIs enhance plasmid packaging efficiency, and phages and PICIs exert selective pressures on plasmids via the physical capacity of their capsids, explaining the bimodal size distribution observed for non-conjugative plasmids. Our results highlight that transducing agents (phages, PICIs) have important roles in bacterial plasmid evolution and, potentially, in antimicrobial resistance transmission.

Highlights

Conjugation has classically been considered the main mechanism driving plasmid transfer in nature
Additional analysis of the 243 plasmids using CONJscan[20] revealed a strikingly low frequency of conjugative plasmids among the dataset, with only 2% (5/243) of plasmids classified as conjugative, while an additional 5 plasmids were identified as having incomplete conjugation systems, suggesting that these could be mobilisable plasmids or are formerly-conjugative plasmids that have lost components
Horizontal transfer of plasmids by conjugation, either autonomously or facilitated in trans, is often considered to be the major mechanism of plasmid transmission, yet horizontally-acquired plasmids have been shown to impose a fitness cost upon their host cell[37,38,39,40,41], indicating that the benefits of horizontal transfer for these plasmids may be somewhat mitigated by a cost to their vertical transmission, though the accessory genes carried by these large plasmids may determine that this cost is still of net-benefit to the host cell under certain conditions

Summary

Introduction

Conjugation has classically been considered the main mechanism driving plasmid transfer in nature. Bacteria frequently carry so-called non-transmissible plasmids, raising questions about how these plasmids spread. We show that phages and PICIs from Staphylococcus aureus can mediate intra- and inter-species plasmid transfer via generalised transduction, potentially contributing to non-transmissible plasmid spread in nature. Since ARGs are mostly carried by plasmids, we must decipher how these mobile genetic elements (MGEs) spread these genes in natural populations of bacteria, promoting the emergence of multi-resistant clones. It has been classically assumed that conjugation is the main mechanism driving plasmid transfer, and drugs blocking this process are currently proposed as an alternative strategy to combat antibiotic resistance[2,3]. Despite the ability of many plasmids to self-transfer and their tendency to confer multi-drug resistances upon their host cell, frequently bacterial pathogens do not carry these elements, implying an inherent cost associated with their carriage[6]. The size distribution of the mobilisable plasmids shows a predominant peak compatible with the size of the phage genomes[10]

Methods

Results

Conclusion