ScienceWise - May/Jun 2008

Keeping one step ahead

In search of a new drug for antibiotic resistant bacteria

Since the dawn of time humans have made use of plants and animals that have natural medicinal properties. Nature provides us with a vast array of potentially useful chemicals, so it’s no surprise that researchers in pharmaceuticals often take a special interest in natural things.

One such researcher is PhD student Kerrie Austin. Kerrie completed her undergraduate studies at the University of Auckland obtaining a first class honours in chemistry. During the summer of her third year, Kerrie visited ANU to undertake a Summer Scholarship at the Research School of Chemistry and enjoyed the experience so much that after completing her honours year in Auckland, she returned to Australia to begin her PhD in the synthesis of compounds found in native flora and fauna.

Kerrie says “I think it’s a good experience to work in many different labs, it increases your knowledge and brings you into contact with other researchers from around the world.” “As a New Zealander moving to Australia, the process is very simple, I was even eligible to apply for an Australian Postgraduate Award Scholarship to fund my studies. It also gave me the chance to do research at a really good university without being too far from home”

Part of her research concerns a natural antibiotic called platencin which is found in some soil microorganisms. Kerrie explains “In the course of this work, we are trying to understand how we can effectively synthesise this molecule from simple and readily available building blocks.

But if compounds like platencin occur naturally, why is it necessary to synthesise them? Often the concentrations of naturally occurring compounds are incredibly low so to extract a few milligrams requires tonnes of raw material. More importantly, many naturally occurring compounds with powerful medicinal qualities have undesirable and even dangerous side effects preventing them from being directly used. But as Kerrie explains “ If we can understand how to synthesise these compounds from scratch, we can usually also design similar compounds called chemical analogues, that have the same benefits without the bad side effects.”

One example of this is the anti acne drug Isotretinoin marketed as Roaccutane. Isotretinoin is chemically similar to vitamin A but modified so that it can be administer in doses that would be toxic or even fatal if the natural vitamin were used. Kerrie has similar hopes for platencin-based antibiotics. “We hope that the work carried out in our group may lead to a marketable antibiotic.”

This kind of research is increasingly important as more and more strains of bacteria are becoming antibiotic resistant. Unfortunately this is an area where nature works against science. When a drug kills 99.999% of a colony of bacteria, the survivors left to breed the next generation are the ones with be best natural resistance. As this process is repeated, the strain evolves an immunity to a particular treatment. The problem is compounded when patients fail to take a complete course of antibiotics as this leaves more surviving bacteria.

Until recently vancomycin was our last line of defence, treating infections caused by resistent strains. However, in the past couple of decades, vancomycin resistant bacteria have been evolving. Platencin offers a different action pathway to most other antibiotics giving it the potential to create a new last line of defence.

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