Volume 95 Issue 17 | News of The Week
Issue Date: April 24, 2017 | Web Date: April 19, 2017

Fungal duo isolated from toxic lake produce novel antibiotic

Berkeley Pit fungi grown together make an antibiotic that fights MRSA
Department: Science & Technology
News Channels: Environmental SCENE, Biological SCENE, Organic SCENE
Keywords: antibiotics, Berkeley Pit, natural product, macrolide, fungus, extremophiles
Montana’s Berkeley Pit is an abandoned mining site with pH 2.5 water.
Credit: Shutterstock
Montana’s Berkeley Pit
Montana’s Berkeley Pit is an abandoned mining site with pH 2.5 water.
Credit: Shutterstock

Two species of fungi isolated from an abandoned mining pit in Montana, when cultured together, produce a compound that kills four antibiotic-resistant strains of Staphylococcus aureus bacteria (J. Nat. Prod. 2017, DOI: 10.1021/acs.jnatprod.7b00133). Although its structure resembles a known class of antibiotics, the compound appears to kill bacteria in a new way, the researchers say.

After companies suspended copper mining at the Berkeley Pit outside of Butte, Mont., in 1983, runoff and groundwater collected in the pit and created a lake. Oxidized rock exposed by mining acidified the water to pH 2.5, and heavy metals including iron, copper, arsenic, and cadmium leached into the water. The water is so toxic that last winter, several thousand snow geese died after waiting out a snowstorm in the pit during their annual migration.

Microbial life, however, finds the pit more hospitable. In extreme environments, such as acidic pH and high metal concentrations, microbes often produce molecules with interesting biological activity. For almost 20 years, Andrea A. Stierle and Donald B. Stierle, both natural products chemists at the University of Montana, have been studying compounds produced by individual fungi isolated from the water and sediment at the Berkeley Pit. They have found molecules that slow inflammation, cell death, and cancer metastasis. But until now, the researchers had not found antibiotics.

The Stierles wondered whether culturing together two different species of Penicillium fungus, originally isolated from the same sample, would produce new bioactive compounds that neither strain makes when grown by itself. They started growing one fungus in a liquid broth and introduced the other species a day later. After the two fungi grew together for six days, the researchers collected the organic molecules the cells produced, extracting them from the broth with chloroform. They used a protein inhibition test the team had developed previously to identify molecules with potential biological activity and then determined the structures of those molecules using various spectroscopic methods. The researchers found a variety of 16-membered macrolides—molecules with a lactone ring—that were not produced when either fungus was grown alone.

Because these structures resembled known antibiotics such as erythromycin, the Stierles and their colleagues tested several of the isolated compounds for antibiotic properties. One compound, Berkeleylactone A, was active against four strains of methicillin-resistant S. aureus.

Structural differences and biochemical tests indicate that this molecule could work differently than similar macrolide antibiotics, Andrea Stierle says. Berkeleylactone A lacks sugars or a double bond, two structural features thought to be important to the antibiotic properties of other 16-member macrolides isolated from bacteria or fungi. And although its exact method of action is unknown, it does not inhibit protein synthesis or stall ribosome activity like other macrolide antibiotics do.

Lesley-Ann Giddings, a natural products chemist at Middlebury College, thinks it’s interesting to co-culture two fungi, because most researchers who have used this strategy to identify new molecules have grown a bacterium and a fungus simultaneously. Co-culturing microorganisms establishes a competition for resources that can trigger one microbe to express otherwise inactive genes and produce compounds that kill the other.

This article has been translated into Spanish by Divulgame.org and can be found here.

Chemical & Engineering News
ISSN 0009-2347
Copyright © American Chemical Society
Joseph J. Lewis (Wed Apr 19 21:14:57 EDT 2017)
It would be interesting to note what biological activity would result from the products of other known macrolide antiobiotics should their double bonds be reduced and/or sugars be removed.
A (Thu Apr 20 17:29:56 EDT 2017)
Better living through toxins?
Sherry Gaddy (Wed Apr 26 10:01:39 EDT 2017)
Wow! This is very cool. I hope this study reaps huge benefits.
Faizunnahar D. (Sat Apr 29 22:08:15 EDT 2017)
What a promising discovery! The dedication of the researchers in studying the compounds from the Berkeley Pit for nearly two decades is truly admirable, and I hope they have many more new, exciting innovations as these.
David R Thomas (Sun Apr 30 08:24:55 EDT 2017)
Very interesting donniker on the Copper mining's behalf. I hope that this will also give weight to the argument of open hazardous pits and wildlife hazards. But with that said, It is good to see science studying these waist lands and waters see who what when where there experiment may be of use. I hope maybe one day that perhaps something of this nature could help the scourge of millions of Tick borne related disease sufferers.
The Lyme and coinfections related to this scourge has only just begun and we are going to watch our children bury their children because of ill practices of our science communities. Perhaps we could start thinking things through, before we create monsters.
Robert C. Reynolds (Sun Apr 30 14:20:55 EDT 2017)
Where did my comment go?
Damon Kelley (Sun May 07 11:10:06 EDT 2017)
Breakthrough water equipment developed by really smart people that listened to environmental activists about fracking concerns will soon be deployed and cleaning up those messes. We're talking about heat so intense, it breaks molecular bonds and carbonizes everything inert. This recently verified, patented technology was studied by Texas A&M's Physical and Environmental Science's own department chairman and has the ability to clean and purify ANY contaminated water ANYWHERE in the world. It also desalinates heavy brine water and sea water. Our machine is so efficient, it even heats water at one-third the cost of conventional equipment. Big change is coming via sonic cavitation.....soon!
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