Replication of IncB and other plasmids

Funded Activity Summary

Plasmids are additional mini-chromosomes carried by many bacteria. They carry information that enables their hosts to prosper in otherwise hostile environments. Plasmids spread rapidly between bacteria, efficiently disseminating plasmid-borne information throughout bacterial populations. Many plasmids carry information that increases the virulence of their host. The emergence of multi-drug resistant bacteria and the rapid spread of the information enabling bacteria to withstand most antibiotics available today, were mediated by plasmids. Plasmids also carry information that ensures their own survival. Consequently, their hosts retain the plasmids even when it is no longer beneficial for them to do so. For example, plasmids mediating resistance to antibiotics are not lost when bacterial hosts are grown in the absence of those antibiotics. That is because plasmids have control systems, which ensure both that replication of the plasmid keeps pace with that of its host, and that the plasmid does not produce so many copies of itself that it overwhelms its host or places it at a competitive disadvantage amongst other bacteria. This project examines the intricate regulatory system that enables two groups of antibiotic-resistance plasmids to ensure that, on average, each plasmid molecule is replicated once per bacterial cell cycle. This system uses a tertiary RNA structure as a molecular switch, an antisense RNA as the regulator of this switch, and a protein that interacts with DNA sequences on the plasmid and with a bacterial protein, to initiate replication. Information gained from studies of plasmid systems is essential to the development of treatments for the elimination of antibiotic-resistance and virulence-contributing plasmids from populations of pathogenic bacteria. Antisense RNAs are not only a powerful research tool, but are also being developed for therapeutic use. Understanding how these RNAs interact with their targets will increase their effectiveness.

Funded Activity Details

Start Date: 01-01-2004

End Date: 01-01-2006

Funding Scheme: NHMRC Project Grants

Funding Amount: $399,750.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Allergy

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

Antisense RNA | Antisense technology | Bacterial plasmids | Basic science | DNA replication | Gene expression | Plasmid-borne virulence genes | Prevention of antibiotic resistance development | Protein expression | Protein-protein interaction

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