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Quantification of Plasmid-Mediated Antibiotic Resistance in an Experimental Evolution Approach
Published on: December 14, 2019
Prevalence and significance of plasmid maintenance functions in the virulence plasmids of pathogenic bacteria
Manjistha Sengupta1, Stuart Austin
1Gene Regulation and Chromosome Biology Laboratory, National Cancer Institute, CCR,NCI-Frederick, Frederick, Maryland 21702-1201, USA.
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.
Insights
Large low-copy-number plasmids use three essential systems to ensure stable inheritance in bacteria. These plasmid-encoded maintenance systems are crucial virulence factors and potential antibacterial targets.
Area of Science:
- Bacteriology
- Molecular Biology
- Genetics
Background:
- Pathogenic bacteria utilize large, low-copy-number plasmids to carry virulence factors, reducing metabolic load.
- These plasmids face segregation challenges during cell division, risking loss.
- Plasmid maintenance systems counteract loss by ensuring inheritance and eliminating plasmid-free cells.
Purpose of the Study:
- To investigate the essentiality of plasmid-encoded systems for stable maintenance of large, low-copy-number plasmids.
- To establish these systems as ubiquitous virulence factors.
- To highlight their potential as targets for novel antibacterial agents.
Main Methods:
- Review and analysis of well-annotated virulence plasmid sequences.
- Comparative genomics to identify conserved plasmid maintenance systems.
- Literature review on plasmid replication, multimer resolution, partition, and postsegregational killing.
Main Results:
- Three key systems—replication, multimer resolution, and partition—are essential for stable plasmid maintenance.
- These systems are frequently found on large virulence plasmids, often with multiple examples.
- Postsegregational killing systems eliminate any resulting plasmid-free cells.
Conclusions:
- Plasmid partition, multimer resolution, and postsegregational killing systems are indispensable for large, low-copy-number plasmid stability.
- These systems function as ubiquitous virulence factors.
- Targeting these essential plasmid maintenance systems offers a promising strategy for developing new antibacterial therapies.
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