Mosaic plasmids are abundant and unevenly distributed across prokaryotic taxa

Mitchell W Pesesky,Rayna Tilley,David A.C Beck

doi:10.1016/j.plasmid.2019.02.003

Abstract

Mosaic plasmids, plasmids composed of genetic elements from distinct sources, are associated with the spread of antibiotic resistance genes. Transposons are considered the primary mechanism for mosaic plasmid formation, though other mechanisms have been observed in specific instances. The frequency with which mosaic plasmids have been described suggests they may play an important role in plasmid population dynamics. Our survey of the confirmed plasmid sequences available from complete and draft genomes in the RefSeq database shows that 46% of them fit a strict definition of mosaic. Mosaic plasmids are also not evenly distributed over the taxa represented in the database. Plasmids from some genera, including Piscirickettsia and Yersinia, are almost all mosaic, while plasmids from other genera, including Borrelia, are rarely mosaic. While some mosaic plasmids share identical regions with hundreds of others, the median mosaic plasmid only shares with 8 other plasmids.When considering only plasmids from finished genomes (51.6% of the total), mosaic plasmids have significantly higher proportions of transposase and antibiotic resistance genes. Conversely, only 56.6% of mosaic fragments (DNA fragments shared between mosaic plasmids) contain a recognizable transposase gene, and only 1.2% of mosaic fragments are flanked by inverted repeats. Mosaic fragments associated with the IS26 transposase gene are 3.8-fold more abundant than any other sequence shared between mosaic plasmids in the database, though this is at least partly due to overrepresentation of Enterobacteriaceae plasmids.Mosaic plasmids are a complicated trait of some plasmid populations, only partly explained by transposition. Though antibiotic resistance genes led to the identification of many mosaic plasmids, mosaic plasmids are a broad phenomenon encompassing many more traits than just antibiotic resistance. Further research will be required to determine the influence of ecology, host repair mechanisms, conjugation, and plasmid host range on the formation and influence of mosaic plasmids. Author summaryPlasmids are extrachromosomal genetic entities that are found in many prokaryotes. They serve as flexible storage for genes, and individual cells can make substantial changes to their characteristics by acquiring, losing, or modifying a plasmid. In some pathogenic bacteria, such as Escherichia coli, antibiotic resistance genes are known to spread primarily on plasmids. By analyzing a database of 8592 plasmid sequences we determined that many of these plasmids have exchanged genes with each other, becoming mosaics of genes from different sources. We next separated these plasmids into groups based on the organism they were isolated from and found that different groups had different fractions of mosaic plasmids. This result was unexpected and suggests that the mechanisms and selective pressures causing mosaic plasmids do not occur evenly over all species. It also suggests that plasmids may provide different levels of potential variation to different species. This work uncovers a previously unrecognized pattern in plasmids across prokaryotes, that could lead to new insights into the evolutionary role that plasmids play.

Highlights

Plasmids are an important source of prokaryotic genetic variation, though they play different roles for different clades
We define a plasmid as mosaic if it contains a region of 500 bp or longer with 100% identity to the sequence of another plasmid, and where those two plasmids have less than 93.90% global sequence identity
We explored two main hypotheses: 1) transposases increase the rate of mosaic plasmid formation, and mosaic plasmids will be enriched for transposases compared to non-mosaic plasmids; and 2) antibiotics create selection pressure for antibiotic resistance gene spread via mosaic plasmids, and mosaic plasmids will be enriched for antibiotic resistance genes compared to non-mosaic plasmids

Summary

Introduction

Plasmids are an important source of prokaryotic genetic variation, though they play different roles for different clades. In the pathogenic members of the Enterobacteriaceae, for instance, plasmids are highly variable and provide their hosts with the opportunity to acquire new genes. In Borrelia, on the other hand, the number of plasmids and their genetic content seem far more consistent between strains (1). These different plasmid roles have important effects on the evolution of these organisms, including the separate pathways by which they can become resistant to antibiotics. Many recently emerged antibiotic resistance genes are primarily found on plasmids, including cephalosporinases such as CTX-M, carbapenemases such as KPC, aminoglycoside acetylases such as aac6’-1b (2), and the colistin resistance gene

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