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Remodeled antibiotic molecules used to battle drug-resistant bacteria

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Sept. 23 (UPI) — Every year, drug-resistant strains of common bacteria cause thousands of premature deaths, and the problem is getting worse, according to researchers.

Drug-resistance has rendered many old treatments obsolete, but new classes of antibiotics have been slow to materialize. To tackle the problem, researchers at the University of California, San Francisco decided to redesign existing antibiotic molecules, instead of inventing new ones.

Scientists described the new approach in a paper published Wednesday in the journal Nature.

“The aim is to revive classes of drugs that haven’t been able to achieve their full potential, especially those already shown to be safe in humans,” lead study author Ian Seiple said in a news release.

“If we can do that, it eliminates the need to continually come up with new classes of drugs that can outdo resistant bacteria. Redesigning existing drugs could be a vital tool in this effort,” said Seiple, an assistant professor of pharmaceutical chemistry at the UCSF School of Pharmacy.

Researchers tested their novel approach on a class of antibiotics called streptogramins, which, until recently, was an effective weapon against Staphylococcus aureus infections. Unfortunately, the bacteria evolved resistance to the antibiotics, forcing doctors to mostly sideline the drugs.

Streptogramins work by attacking a bacteria’s ribosome, preventing the bacteria from synthesizing proteins. Staphylococcus aureus eventually grew wise to the strategy.

Now, drug-resistant strains of the bacteria produce proteins called virginiamycin acetyltransferases, or Vats, which recognize and chemically disarm the drug molecules upon entering the bacterial cell.

Like many antibiotics, streptogramins are made by tweaking naturally occurring antibiotic molecules, which are typically produced by other types of bacteria. Scientists hypothesized that additional designs change might help the antibiotic evade Vats.

Instead of augmenting streptogramin molecules, researchers decided to entirely rebuild the antibiotic. To simplify the process, they created seven molecular modules, or streptogramin prototypes, that could be further customized.

“This system allows us to manipulate the building blocks in ways that wouldn’t be possible in nature,” said Seiple. “It gives us an efficient route to re-engineering these molecules from scratch, and we have a lot more latitude to be creative with how we modify the structures.”

Once researchers had some basic molecular building blocks to work with, they used computer models to visually understand how they might fit together and tweak them in order to create a new and effective antibiotic molecule.

“My lab’s contribution was to say, ‘Now that you’ve got the seven pieces, which one of them should we modify and in what way?'” said study co-author James Fraser, professor of bioengineering and therapeutic sciences in the UCSF School of Pharmacy.

Visual modeling helped Seiple, Fraser and their colleagues figure out which parts of the streptogramin molecules are essential to its antibiotic qualities and which non-essential parts could be manipulated to prevent Vats interference.

Using what they learned, researchers synthesized several new streptogramin molecules and tested them against drug-resistant S. aureus in infected mice. The most promising candidate was ten times more effective than traditional streptogramin drugs.

According Seiple, the team’s research can serve as a blueprint for modifying other classes of antibiotics.

“We learned about mechanisms that other classes of antibiotics use to bind to the same target,” he said. “In addition, we established a workflow for using chemistry to overcome resistance to antibiotics that haven’t reached their potential.”

Ultimately, scientists hope that by studying the molecular mechanics of previously effective antibiotics, they can design more effective drugs.

“It’s a never-ending arms race with bacteria,” said Fraser. “But by studying the structures involved — before resistance arises — we can get an idea of what the potential resistance mechanisms will be. That insight will be a guide to making antibiotics that bacteria can’t resist.”



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NASA’s OSIRIS-REx touches down on asteroid Bennu to nab sample

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Oct. 20 (UPI) — NASA’s OSIRIS-REx touched down on asteroid Bennu on Tuesday evening in a mission to scoop a sample of rocks and dirt.

The spacecraft — the Origins, Spectral Interpretation, Resource Identification, Security, Regolith Explorer — made soft contact with the asteroid at 6:12 p.m. EDT.

The historic “touch and go” event featured animation displaying OSIRIS-REx’s sample collection activities in real time. It takes time for real images of the touchdown to travel back to the Earth, so they won’t be released to the public until Wednesday.

The craft executed a series of maneuvers over the course of several hours before making soft contact with the surface of the asteroid to collect regolith, or rocks and dirt.

“It will be four and a half hours of anxiousness,” Beth Buck, OSIRIS-REx mission operations manager at Lockheed Martin Space, said in a news conference ahead of the event.

Buck made a comparison to the descent of a spacecraft on Mars, when there is typically “seven minutes of terror.”

The goal is to learn more about the solar system’s history and help “planetary defense” engineers with missions to protect earth from rogue asteroids. Bennu is believed to be a window into the solar system’s past since it’s a pristine, carbon-rich body carrying building blocks of both planets and life.

At around 1:50 p.m. EDT, the spacecraft left orbit around the asteroid before executing a series of burns to position itself over a sampling area nicknamed Nightingale.

Once in position, the craft began its approach to the asteroid at 5:50 p.m. EDT. It then spent about 15 seconds attempting to collect the regolith sample before backing away again.

The area, which is 52 feet in diameter, will make for a more demanding landing than expected, Kenneth Getzandanner, OSIRIS-REx flight dynamics manager at the NASA Goddard Space Flight Center in Maryland, said in the news conference.

The original mission called for a landing “zone” about 150% larger than Nightingale, at 82 feet, but that changed because Bennu was more rocky than expected.

The goal was to collect at least 1.7 ounces of fine-grained material, but the spacecraft can carry up to 4.4 pounds, Heather Enos, OSIRIS-REx deputy principal investigator at the University of Arizona said.

“I would love for that capsule to be completely full,” Enos said.

Though early images from the asteroid should hint at whether the mission succeeded, it will take engineers roughly 10 days to compare and analyze the mass before and after the maneuver to actually know how much dirt is inside the OSIRIS-REx.

If it failed, the spacecraft has enough fuel to attempt two more touch downs to collect material.

The spacecraft is expected to return to Earth, with the regolith sample from Bennu, in 2023.



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SpaceX scrubs Starlink launch until Thursday, if weather cooperates

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Oct. 21 (UPI) — Just three days after sending 60 more Starlink satellites into orbit, SpaceX is aiming to launch another batch of broadband satellites into space from Florida.

If the weather cooperates, Thursday’s launch will be SpaceX’s 15th Starlink mission.

Liftoff had been scheduled for 12:29 p.m. EDT Wednesday aboard a Falcon 9 rocket at Launch Complex 40 at Cape Canaveral Air Force Station, but controllers scrubbed the launch due to weather and rescheduled for 12:14 p.m. on Thursday.

With a launch Sunday, SpaceX increased the size of their Starlink constellation to nearly 800 satellites. The 15th mission will see another 60-odd satellites join the network.

“The goal of Starlink is to create a network that will help provide Internet services to those who are not yet connected, and to provide reliable and affordable Internet across the globe,” according to the Kennedy Space Center.

Weather for Wednesday’s planned launch had looked so-so and the Space Force’s 45th Weather Squadron predicted a 60 percent chance of favorable conditions.

“A mid-level inverted trough and associated easterly wave currently across the Bahamas will meander into the state over the next few days, bringing enhanced moisture, cloud cover, and instability with a higher coverage of showers and storms,” Space Force forecasters wrote.

They said Thursday’s forecast looks quite similar to Wednesday’s.

Earlier this month, SpaceX founder and CEO Elon Musk tweeted that Starlink’s constellation was big enough to begin beta-testing the Internet service system in both the United States and southern Canada.

SpaceX has already offered Starlink Internet services to emergency responders in wildfire-stricken areas of Washington State.

Washington’s Hoh tribe is also using the Internet service to provide their members online education and telehealth services.



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Chernobyl-level radiation harms bumblebee reproduction

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Oct. 21 (UPI) — Bees are more sensitive to radiation than scientists thought. Scientists found the reproduction rates of bumblebees declined significantly when exposed to Chernobyl-level radiation.

The research, published Wednesday in the journal Proceedings of the Royal Society B: Biological Sciences, suggests radiation in Ukraine’s Chernobyl Exclusion Zone could impair pollination services, triggering wider ecological consequences than previously estimated.

Humans are not allowed to live in the Chernobyl Exclusion Zone, the disaster area more directly impacted by the 1986 nuclear accident, the worst in history. However, the destroyed nuclear reactors are surrounded by forests that are populated by robust populations of birds, bears, bison, lynx, moose, wolves and more.

Efforts to gauge the effects of radiation contamination on insects have yielded mixed results in the past. While some studies have suggested insects are relatively radiation-resistant, others have demonstrated significant impairment.

When researchers exposed bumblebees in the lab to radiation dose of 100 µGyh-1, an amount approximating exposure inside the Chernobyl Exclusion Zone, reproduction rates among the bees dropped between 30 and 45 percent.

Researchers found a direct correlation between the size of the radiation dose and reproduction rate declines. Lower levels of radiation had a smaller effect, while larger doses yielded greater declines.

Scientists were surprised to find they were able to detect reproductive rate declines at very small levels of radiation exposure.

“Our research provides much needed understanding as to the effects of radiation in highly contaminated areas and this is the first research to underpin the international recommendation for the effects of radiation on bees,” lead study author Katherine Raines, environmental scientist at the University of Stirling in Scotland, said in a news release.



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