Novel compounds for use as inhibitors of virulence of human pathogens

Funded Activity Summary

There is growing concern over the emergence of multi-drug resistant strains of bacteria which are no longer treatable with the current generation of antibiotics. This highlights the urgent need for development of the next generation of therapeutic agents to supplement or replace the current antibiotics. Our research team has identified a class of compounds which are naturally produced by a marine alga that may be effective in the control of bacterial pathogens. These compounds work by interfering with the way many pathogens regulate the production of virulence traits. Some bacteria are able to signal members of their population by the specific uptake and recognition, through a receptor protein, of chemical cues they secrete into the environment. Accumulation of these cues or signals triggers expression of the genes that code for the virulence traits. Moreover, one particular class of these signal response proteins has been identified in many pathogens and has been shown to regulate protease production and production of a protective extracellular slime layer called a capsule. If one or more of these traits can be blocked, then the virulence of the bacterium can be reduced. We have preliminary data which demonstrates that the algal compounds do in fact prevent the expression of virulence traits and thus should be useful as new agents for the treatment of disease. The causative agents of cholera and severe gatroenteritis, Vibrio cholerae and V. parahaemolyticus respectively, have one or the other of these virulence traits, but the pathogen Vibrio vulnificus has all three and therefore is an excellent model pathogen. We propose to explore the ability of the algal compounds to specifically shut down expression of virulence factors with a long term aim for the development of these compounds as novel antimicrobial therapies for the post-antibiotic era.

Funded Activity Details

Start Date: 01-01-2003

End Date: 01-01-2005

Funding Scheme: NHMRC Project Grants

Funding Amount: $220,500.00

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

Anti-microbial therapy | Bacterial pathogens | Cell-cell communication | Inhibition of virulence factor expression | Inter-cellular signalling | Multi-drug resistance | Novel therapeutic agents | Pathogenic bacteria | Regulationo of virulence in pathogens

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