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ANTIBIOTICS
Fungal duo from toxic lake produces novel antibiotic
CREDIT: SHUTTERSTOCK
Berkeley Pit fungi grown together make a compound that fights antibiotic-resistant bacteria Two species of fungi isolated from an sample, would produce new bioactive abandoned mining pit in Montana, when compounds that neither strain makes when cultured together, produce a grown by itself. They started compound that kills four antibigrowing one fungus in a liquid otic-resistant strains of Staphy- HO broth and introduced the other lococcus aureus bacteria (J. Nat. species a day later. After the O Prod. 2017, DOI: 10.1021/acs. two fungi grew together for six O jnatprod.7b00133). Although its days, the researchers collected O S structure resembles a known the organic molecules the cells class of antibiotics, the comproduced, identified molecules OH C pound appears to kill bacteria in HO with potential biological activa new way, the researchers say. ity, and then determined the O After companies suspended structures of those molecules Berkeleylactone A copper mining at the Berkeley using various spectroscopic Pit outside Butte, Mont., in 1983, runoff and methods. The researchers found a variety groundwater collected in the pit and creatof 16-membered macrolides—molecules ed a lake. Oxidized rock exposed by mining with a lactone ring—that were not proacidified the water to pH 2.5, and heavy duced when either fungus was grown alone. metals including iron, copper, arsenic, and Because these structures resembled cadmium leached into the water. Also in known antibiotics such as erythromycin, the 1983, it was designated a Superfund site. Stierles and their colleagues tested several 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. 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 species of Penicillium fungus, originally isolated from the same
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 and a double bond, two structural features thought to be important to the antibiotic properties of other 16-membered 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 see the results of a coculture of two fungi. Coculturing microorganisms establishes a competition for resources that can trigger one microbe to express otherwise inactive genes and produce compounds that kill the other.—MELISSAE
FELLET, special to C&EN
Montana’s Berkeley Pit is an abandoned mining site with pH 2.5 water.
APRIL 24, 2017 | CEN.ACS.ORG | C&EN
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