Gene and cell survival: lessons from prokaryotic plasmid R1

Abstract

Plasmids are units of extrachromosomal genetic inheritance found in all kingdoms of life. They replicate autonomously and undergo stable propagation in their hosts. Despite their small size, plasmid replication and gene expression constitute a metabolic burden that compromises their stable maintenance in host cells. This pressure has driven the evolution of strategies to increase plasmid stability-a process accelerated by the ability of plasmids to transfer horizontally between cells and to exchange genetic material with their host and other resident episomal DNAs. These abilities drive the adaptability and diversity of plasmids and their host cells. Indeed, survival functions found in plasmids have chromosomal homologues that have an essential role in cellular responses to stress. An analysis of these functions in the prokaryotic plasmid R1, and of their intricate interrelationships, reveals remarkable overall similarities with other gene-and cell-survival strategies found within and beyond the prokaryotic world. Keywords: plasmid R1; stability system; parD; toxin-antitoxin pair; RNA decay EMBO reports (2007) 8, 458-464. doi:10.1038/sj.embor.7400957 R1 architecture: a winning design for DNA survival Plasmid R1 is a good example of how the need to be stably maintained in host cells shapes the architecture and building blocks of extrachromosomal elements. Four properties can be distinguished in R1, all of which contribute to plasmid survival: antibiotic-resistance genes, horizontal DNA transfer genes, stability systems and the basic replicon (Fig 1A;Womble & Rownd, 1988).R1 carries ampicillin-(bla), chloramphenicol-(cat), kanamycin-(aph), streptomycin/spectinomycin-(aad ) and sulfonamide-(sul ) resistance genes. These are clustered in the R-determinant, which contains three insertion sequences and a transposon, Tn4. Insertion sequences are minimal transposable elements that encode functions involved in insertion events, and they are found in plasmids and in the chromosomes of prokaryotes, eukaryotes and archaea (Mahillon & Chandler, 1998). They mediate various DNA rearrangements, including the integration of R1 into host chromosomes, which can also influence the transcription of neighbouring genes. Genes flanked by two identical insertion sequences become transposable elements; therefore, antibiotic-resistance genes in R1 can be mobilized as transposons in different combinations.R1 can also move horizontally into plasmid-free cells by conjugation. To achieve this, R1 induces the synthesis of a pilus that attaches the donor to a recipient cell. One DNA strand of R1 is then cleaved at oriT (origin of transfer) and transferred through the pilus to the recipient cell, in which it is re-circularized and converted into double-stranded DNA. Most genes required for transfer are encoded in the tra operon. In R1, a regulatory network inhibits expression of this operon, limiting the frequency of conjugation to 1×10 -3 per R1 copy. However, once transfer occurs, the absence of the limiting regulatory factors in recipient ...

Conjugative plasmids: vessels of the communal gene pool

“…(b) Organization of conjugative plasmids Plasmids have long been considered to be modular in nature since they often contain discrete regions of genes, clustered together in functional groups, that are responsible for various aspects of plasmid maintenance and propagation (Thomas, 2000;de la Cueva-Méndez & Pimentel 2007). Plasmids are therefore said to consist of a 'backbone' of plasmid-selfish modules (figure 4), often combined with a block of 'accessory elements' containing mosaics of translocative elements and operative elements that encode beneficial traits for the host cell and, potentially, other resident prokaryotes, within specific environmental niches (Eberhard 1990).…”

Engineering of a Highly Efficient Escherichia coli Strain for Mevalonate Fermentation through Chromosomal Integration

“…Although plasmid-based production of mevalonate achieved high yields, the disadvantages of plasmid-based fermentation pose significant challenges for large-scale fermentation (11)(12)(13)(14)(15). First, the replication of plasmid and expression of the genes residing on the plasmid result in extra metabolic burden, which reduces the allocation of nutrient and energy resources for the desired product (12).…”

Toxin Kid uncouples DNA replication and cell division to enforce retention of plasmid R1 in Escherichia coli cells

“…Alternatively, some TA pairs may stabilize plasmids by mechanisms different from PSK, and their grouping might not necessarily reflect functional redundancy (18).…”