Virulence Plasmids of Spore-Forming Bacteria
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Published on: June 25, 2016
Vicki Adams1, Jihong Li2, Jessica A Wisniewski1
1Australian Research Council Centre of Excellence in Structural and Functional Microbial Genomics, Department of Microbiology, Monash University, Clayton, Vic 3800, Australia.
Abstract:
Plasmid-encoded virulence factors are important in the pathogenesis of diseases caused by spore-forming bacteria. Unlike many other bacteria, the most common virulence factors encoded by plasmids in Clostridium and Bacillus species are protein toxins. Clostridium perfringens causes several histotoxic and enterotoxin diseases in both humans and animals and produces a broad range of toxins, including many pore-forming toxins such as C. perfringens enterotoxin, epsilon-toxin, beta-toxin, and NetB. Genetic studies have led to the determination of the role of these toxins in disease pathogenesis. The genes for these toxins are generally carried on large conjugative plasmids that have common core replication, maintenance, and conjugation regions. There is considerable functional information available about the unique tcp conjugation locus carried by these plasmids, but less is known about plasmid maintenance. The latter is intriguing because many C. perfringens isolates stably maintain up to four different, but closely related, toxin plasmids. Toxin genes may also be plasmid-encoded in the neurotoxic clostridia. The tetanus toxin gene is located on a plasmid in Clostridium tetani, but the botulinum toxin genes may be chromosomal, plasmid-determined, or located on bacteriophages in Clostridium botulinum. In Bacillus anthracis it is well established that virulence is plasmid determined, with anthrax toxin genes located on pXO1 and capsule genes on a separate plasmid, pXO2. Orthologs of these plasmids are also found in other members of the Bacillus cereus group such as B. cereus and Bacillus thuringiensis. In B. thuringiensis these plasmids may carry genes encoding one or more insecticidal toxins.
Insights
Spore-forming bacteria like Clostridium and Bacillus use plasmid-encoded toxins for virulence. Understanding how these bacteria maintain toxin-encoding plasmids is crucial for disease control.
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Molecular Biology
Background:
- Spore-forming bacteria, including Clostridium and Bacillus species, utilize plasmid-encoded virulence factors, primarily protein toxins, for pathogenesis.
- Clostridium perfringens produces various toxins (e.g., enterotoxin, epsilon-toxin, beta-toxin, NetB) involved in histotoxic and enterotoxin diseases.
- Toxin genes are typically located on large conjugative plasmids with conserved replication, maintenance, and conjugation regions.
Purpose of the Study:
- To investigate the role of plasmid-encoded virulence factors in spore-forming bacteria.
- To explore the mechanisms of plasmid maintenance in Clostridium perfringens, particularly the stable maintenance of multiple toxin plasmids.
- To examine the genetic basis of toxin production in other medically relevant bacteria like Clostridium tetani, Clostridium botulinum, and Bacillus anthracis.
Main Methods:
- Genetic studies to determine the role of toxins in disease.
- Analysis of plasmid replication, maintenance, and conjugation regions.
- Comparative genomics of toxin-encoding plasmids across different bacterial species.
Main Results:
- Plasmid-encoded protein toxins are common virulence factors in Clostridium and Bacillus species.
- Genes for toxins like C. perfringens enterotoxin, epsilon-toxin, beta-toxin, and NetB are plasmid-borne.
- While conjugation loci are understood, plasmid maintenance mechanisms, especially for multiple plasmids in C. perfringens, require further investigation.
- Toxin gene location varies in neurotoxic clostridia; Bacillus anthracis virulence is plasmid-determined (pXO1 for toxins, pXO2 for capsule).
Conclusions:
- Plasmid-encoded toxins are central to the virulence of many spore-forming bacteria.
- Understanding plasmid maintenance is key to explaining the stable co-existence of multiple virulence plasmids in pathogens like C. perfringens.
- Plasmid and chromosomal elements contribute to virulence across diverse spore-forming genera.
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