Searching remote regions to find new ways to fight Infection

Bioactive Natural Products

John Sorensen and Michele Piercey-Normore, researchers in the departments of Chemistry and Biological Sciences, are studying bioactive natural products made by lichens in a collaborative search to find new antibiotics that can be used to fight infection.

One of the best known bioactive natural products is the antibiotic penicillin G, which is produced by various species of the Penicillium fungus.  However, because of the well-known problems with resistance to penicillin, and the emergence of superbugs, there is an urgent need to find new sources of antibiotics.

Finding the Fungi

A first step in the research is identifying fungi that can produce unique natural products, and this is where Piercey-Normore’s lichens come in.  Lichens are the result of a symbiotic relationship between a fungal partner and algal partner, and Piercey-Normore is the curator of an extensive and unique collection of lichens sampled from across North America, including the sub-arctic regions of Manitoba. 

In addition to collecting the lichens, Piercey-Normore studies the fungal partner in the lichen to understand how the natural products are produced at the cellular level, and what type of environmental changes affect their production. Sorensen samples the attached soil beneath the lichen, which has the potential to contain new strains of fungi that possess the ability to produce new antibacterial natural products.

The soil and lichen fungi under study are important for two reasons. First, they have been collected from regions in Manitoba, like Wapusk National Park near Churchill MB, that are isolated and geographically unique.  Piercey-Normore flies into this remote area on board a Parks Canada helicopter, accompanied by a park warden, armed with a shotgun, binoculars, and knowledge of northern animal behaviour – like polar bears!  Some of the soil and lichen fungi may be unusual in this geographic region and will potentially produce unique natural products with new biological activities.

Second, the fungi have adapted to survive in cold environments and in the presence of slow-growing organisms. This process results in the creation of an ecological micro-environment where lichen and soil fungi have learned to survive, making unique, and increasing numbers of undiscovered natural products.

Studying Fungi in the Lab

Researchers in Sorensen’s lab take these naturally occurring fungi, and grow them in fermentation cultures in their lab, with the goal of finding novel natural products that have potent antibacterial activity and that could ultimately be developed into new sources of treatment for infections.  To accelerate the process, Sorensen is expecting the delivery of $400,000 of equipment funded by the Canada Foundation for Innovation and the Manitoba Research and Innovation Fund.

Students in Piercey-Normore's lab study the genes that produce these compounds. Large clusters of genes produce these compounds but little is known about how they are regulated or what types of environmental conditions will increase production of the compounds. The expression of these genes is studied by examining RNA transcripts and the natural products from fungi that are grown under different nutrient and light conditions. If optimal conditions can be identified from these studies, we can trick the fungi into producing larger quantities of the compounds and better understand the genetic regulation of expression of the genes that produce natural products.

Even though the research is at an early stage for industry, they are making scientific progress, publishing their work, and making unexpected additional discoveries, such as a fungus that converts amino acids into alcohols and the presence of many copies of the genes in the same organism. The projects include a number of undergraduate and graduate students participating directly in the research, one of whom is part of an invention disclosure, which is the first step towards a patent.

We gratefully acknowlege Parks Canada for their support in providing access to Wapusk National Park where collections of lichens have been gathered.

Helicoptor

Michele Piercey-Normore in Wapusk National Park


 Sorensen

John Sorensen, Chemistry, Michele Piercey-Normore, Biological Sciences


How common are natural products drugs?

Over 25 % of all prescription drugs in current use are natural products. The biologically active molecules are purified directly from the large-scale fermentation culture of the producing organism.

The beta-lactam family of antibiotics, of which penicillin is a member, is still one of the most widely used classes of natural product-derived drugs. The carbapenems, also a member of the beta-lactam family, are often used as a ‘last resort’ to treat infections resistant to other antibiotics


What's the fuss about "superbugs"

The newly identified “superbugs” – those that possess the NDM-1 gene – are a major concern because they are resistant to these carbapenem antibiotics. This means that there are only a limited number of antibiotics that can be used to treat infections with NDM-1 superbugs.


Why fungi?

Fungi have developed the ability to produce antibiotics as a means to provide a competitive advantage in the environment. Killing of their bacterial competitors means that the fungi do not have to compete for resources such as nutrients in the environment. These natural antibiotics represent one of the most promising places to look for new treatments for infection.

Lichen fungi are known to produce more than 800 compounds that are uniquely produced only by fungi that form lichen associations. No other organism is known to produce these natural products.

Many of the natural products produced by lichen fungi are produced by the same biosynthetic pathway that produces penicillin and are, therefore, thought to have similar antibacterial and other biologically active properties.