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New chemical from Antarctic sponge extract kills MRSA biofilm
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Recent findings by University of South Florida and University of Alabama at Birmingham researchers showed that an extract from a sponge in Antarctica called Dendrilla membranosa emits a newly discovered chemical that destroys 98% of MRSA cells and is effective toward the biofilm form of the pathogen. The researchers have named the chemical darwinolide.
“When we screened darwinolide against MRSA, we found that biofilms were fourfold more sensitive than free-living bacterial cells,” Bill J. Baker, PhD, professor of chemistry and director of the University of South Florida (USF) Center for Drug Discovery and Innovation, said in a press release. “This suggests that darwinolide may be a good foundation for an urgently needed antibiotic effective against biofilms.”
Bill J. Baker
Figure 1. This is Dendrilla membranosa, near Palmer Station, Antarctica.
Source: Bill J. Baker, PhD
Bacterial biofilms, formed by pathogens such as Staphylococcus aureus, cause up to 80% of all infections and “are recalcitrant to therapeutic intervention,” the researchers wrote. Because MRSA is becoming increasingly resistant to its first-line treatment vancomycin, the researchers sought to develop a new anti-biofilm agent to treat it.
At Palmer Station, Antarctica, USF and UAB researchers studied the local chemical ecology by retrieving marine invertebrates in waters near the station. They retrieved a D. membranosa sponge, which was freeze-dried and subjected to extraction. The researchers purified the extract to yield four natural products, three of which were already known spongian diterpenes. The fourth was a new, rearranged spongian diterpene, which they called darwinolide. Spongian diterpenes tend to be bioactive, so the researchers tested it against MRSA.
According to Baker and colleagues, only 1.6% of MRSA cells were able to grow in vitro against darwinolide, with an IC50 value of 33.2 µM toward the biofilm. In addition, they found that J774 macrophage cells could grow in vitro against darwinolide, with an IC50 value of 73.4 µM, suggesting that darwinolide would not harm humans. They compared darwinolide with other biofilm inhibitors and found that it was less potent, but more selective for biofilm over planktonic cells.
Based on darwinolide’s fourfold selectivity for MRSA over planktonic cells and its low mammalian cytotoxicity, the researchers suggested that darwinolide could become a template for new antibiotics.
“Biofilms, formed by many pathogenic bacteria during infection, are a collection of cells coated in a variety of carbohydrates, proteins and DNA,” Lindsey N. Shaw, PhD, associate professor in the department of cell biology, microbiology and molecular biology at USF, said in the release. “We desperately need new anti-biofilm agents to treat drug-resistant bacterial infections like MRSA.” – by Will Offit
Disclosure: The researchers report no relevant financial disclosures.
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