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Review
. 2011 Jul;79(7):2502-9.
doi: 10.1128/IAI.00127-11. Epub 2011 May 9.

Prevalence and significance of plasmid maintenance functions in the virulence plasmids of pathogenic bacteria

Manjistha Sengupta  1 , Stuart Austin
Affiliations
Review

Prevalence and significance of plasmid maintenance functions in the virulence plasmids of pathogenic bacteria

Manjistha Sengupta et al. Infect Immun. 2011 Jul.

Abstract

Virulence functions of pathogenic bacteria are often encoded on large extrachromosomal plasmids. These plasmids are maintained at low copy number to reduce the metabolic burden on their host. Low-copy-number plasmids risk loss during cell division. This is countered by plasmid-encoded systems that ensure that each cell receives at least one plasmid copy. Plasmid replication and recombination can produce plasmid multimers that hinder plasmid segregation. These are removed by multimer resolution systems. Equitable distribution of the resulting monomers to daughter cells is ensured by plasmid partition systems that actively segregate plasmid copies to daughter cells in a process akin to mitosis in higher organisms. Any plasmid-free cells that still arise due to occasional failures of replication, multimer resolution, or partition are eliminated by plasmid-encoded postsegregational killing systems. Here we argue that all of these three systems are essential for the stable maintenance of large low-copy-number plasmids. Thus, they should be found on all large virulence plasmids. Where available, well-annotated sequences of virulence plasmids confirm this. Indeed, virulence plasmids often appear to contain more than one example conforming to each of the three system classes. Since these systems are essential for virulence, they can be regarded as ubiquitous virulence factors. As such, they should be informative in the search for new antibacterial agents and drug targets.

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Figures

Fig. 1.
Fig. 1.
(A) The Cre/loxP multimer resolution system of P1 has a loxP site 434 bp upstream of the cre gene (green box). It consists of two inversely oriented 13-bp recombinase binding motifs (red solid arrows) flanking an asymmetrical 8-bp sequence. (B) Genetic organization of PSK loci. The pAD1 par system consists of the fst gene (yellow box) encoding RNA I. RNA II is transcribed convergently and shares a bidirectional terminator sequence (gray solid arrows) and direct repeats at 3′ and 5′ ends (blue arrowheads). RNA II and I (dashed arrows) form a stable pair and inhibit fts translation. In plasmid-free cells, RNA II degrades rapidly, causing expression of the toxic Fst protein and resulting in cell death. The ccd system of the F plasmid consists of two genes, ccdB, encoding the killer, and ccdA, encoding the antidote. CcdA binds to CcdB and inhibits cell killing. In the case of plasmid loss, CcdA is rapidly degraded, causing CcdB-mediated cell death. The operon is autoregulated by the protein complex. (C) Genetic organization of the different types of partition systems found in plasmids. The green boxes and the orange boxes represent the centromere-binding protein and the motor protein, respectively. The centromere sequence has been marked by purple boxes. Red arrows mark the direction of transcription. Transcriptional repression and centromere binding have been marked in each case.
Fig. 2.
Fig. 2.
How plasmid maintenance systems combine to achieve stable plasmid inheritance. The cell cycle of typical cells (blue cells) containing a low-copy-number plasmid is represented on the left. Plasmid replication doubles the number of plasmids in each cell. Some cells contain plasmid dimers formed by generalized recombination. These are reduced to monomers by the multimer resolution system. The replicated plasmids are subjected to active partition to opposite cell halves, ensuring that cell division produces two cells, each of which contains at least one plasmid copy. The gray cells represent those rare cells where the replication, multimer resolution, or partition system of the plasmid has failed to function properly. In each case, cell division produces one plasmid-containing cell that is returned to the general population and one that has no plasmid copy. Postsegregation killing is triggered in the latter cells, killing them and thus ensuring that all viable cells in the population retain the plasmid.
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