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Sea squirts against fungi; keeping mice up all night; 3D COVID-19 cells

A new antifungal compound from the microbiomes of a sea squirt that can help combat drug-resistant strains of fungi was discovered by a team of scientists from the University of Wisconsin-Madison.

SNL Image

Scientists are exploring the Florida Keys as part of a mission to find previously-undiscovered antimicrobials in different ecosystems.
Source: John M Lund Photography Inc/DigitalVision via Getty Images

Many disease-causing fungi have evolved to be resistant to drugs, which researchers said has caused people to die from previously-treatable diseases like yeast infections or aspergillosis, an infection caused by mold.

The scientists discovered the compound in the Florida Keys as part of a mission to find previously-undiscovered antimicrobials in different ecosystems. Scientists collected ocean-dwelling invertebrates in the Florida Keys between 2012-2016 and then identified and grew nearly 1,500 strains of actinobacteria. The scientists then tested 174 of these strains against a drug-resistant strain of the fungus Candida.

In lab experiments, the antifungal from the sea squirt, dubbed turbinmicin, was found to be the most effective. In the lab, it halted or killed nearly all fungal strains at a low concentration.

"Bacteria in particular are rich sources of molecules. But a lot of the terrestrial ecosystems have been pretty heavily mined for drug discovery," said Tim Bugni, a professor in the UW–Madison School of Pharmacy who led the turbinmicin project. "There's immense bacterial diversity in the marine environment and it's barely been investigated at all."

Additional tests in mice infected with drug-resistant strains of the fungi Candida auris and Aspergillus fumigatus showed that turbinmicin was not only effective in attacking the strains but was also not toxic in the mice even at doses 1,000 times greater than the minimum dose. In adults, turbinmicin could be effective at a much lower dosage than many other antibiotics.

The researchers have filed a patent for turbinmicin and are making small alterations to make it an effective drug.

Up all night

Researchers from the Perelman School of Medicine at the University of Pennsylvania identified a group of neurons in mice that can keep them from falling asleep and even wake them from anesthetics.

"Our findings add to evidence that the neural circuits regulating wakefulness may also be important for the exit from general anesthesia," Max Kelz, senior author and professor at Penn Medicine, said in a Nov. 18 statement.

In the study, published in Current Biology on Nov. 13, a group of mice were given a chemical called CNO that allowed the Tac1 neurons in the preoptic area of the brain to be turned on for a few hours. Researchers then observed the mice over a four-hour session. While the control mice slept for about 40% of that time, the POA Tac1-activated mice stayed awake for most of the recorded period.

Researchers then ran further tests that demonstrated the POA Tac1-activated mice required higher doses of general anesthesia to become unconscious and were able to wake from general anesthesia at levels that would previously have kept them unconscious.

The findings could potentially help create drugs to speed up the wakening process after a patient receives anesthesia or for patients who suffer from narcolepsy, a chronic sleep disorder that causes patients to fall asleep suddenly at any hour of the day.

COVID-19 under the microscope

SNL Image
Cells that are infected with the SARS-CoV-2 virus die within 24 to 48 hours after infection.
Source: Andriy Onufriyenko/Moment via Getty images

A team of researchers from the European Molecular Biology Laboratory and Heidelberg University created 3D images of cells infected with COVID-19 to see how the virus changes them.

Cells infected with the virus die quickly, within 24 to 48 hours after infection. The researchers therefore wanted to examine how the virus reprograms cells to reproduce itself. Professor Ralf Bartenschlager of Heidelberg University said creating therapies that can suppress this replication is key to understanding and combating the virus' replication cycle.

The 3D images revealed "massive" changes to the cells' endomembrane systems. When infected by the virus, compartments are created in the membrane where the viral genome can replicate. After replication, the viral genomes are released to become part of new virus particles.

"We saw how and where the virus replicates within the cell, and how it hijacks its host machinery to be released after multiplication," the team said in a Nov. 23 statement.

The team has made the 3D structural information available for other researchers and scientists.