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Hijacked Bacteria Reveal New Compounds, New Drug Candidates

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More than half of all new drugs in the U.S. are made from compounds found in nature. These so-called secondary metabolites are produced in the cells of plants and microorganisms like bacteria. You certainly know the most famous ones: household names like caffeine, aspirin and penicillin. There’s the lycopene in tomatoes, resveratrol in grapes, and don’t forget the cocaine in coca leaves or the morphine found in poppies. Now, scientists have figured out a new way to tap into a major source of these compounds, which could hold promise for future drug development. The new method has already revealed nine new compounds, one of which has strong antiviral properties.

In nature, secondary metabolites are produced for some biological function. They can give a flower a red color that attracts hummingbirds, give a plant a bad taste so it won’t get eaten, or provide bacteria with a powerful weapon against rival bacteria. The latter is where many antibiotics come from.

Sometimes, an organism produces these secondary metabolites only some of the time, if it’s triggered by something. In these cases, the organism has the instructions on how to make the compound in its DNA, but it’s switched off. Until something happens to it that turns it on.

Unlocking Hidden Bacteria Compounds

Before this new development, scientists could only study these “silent” secondary metabolite compounds through complex genetics work. For example, they might have to start by sequencing an entire bacterial genome. From there, they could figure out which genes had unknown functions. Then to study the mystery genes, they could transfer them, one by one, into a different bacteria and try to turn them on. This process was incredibly slow and arduous.

That’s why chemists Fei Xu and Yihan Wu wondered if they could speed this up. The Princeton University group recently published their work in Nature Chemical Biology.

They built on a method developed in 2014 by Mo Seyedsayamdost, the leader of the research group, called elicitor screening. Put simply, it’s a way of exposing bacteria to various compounds to see what elicits a response.

“The limitation is sometimes we find elicitors and can activate the gene pathways … but it’s hard for us to find the real products, the real compounds” says Xu. He explains that simply figuring out how to “turn on” the gene doesn’t give a straightforward answer on what secondary metabolites will be produced.

“So to solve this problem, so we wanted to find a new method that can just skip this step,” says Xu. In other words, without doing any genetics work, just trigger the genes to turn on and measure the compounds that get made at the end.

So they ramped the elicitor screening idea way up. They figured out a way to throw 500 of these potential gene triggers at multiple strains of bacteria, individually and in combination, and then screen for all the secondary metabolite compounds the bacteria produced in response.

A New Source for Potential Drugs

It not only worked — it was incredibly fruitful. The group identified nine new secondary metabolites. That’s nine compounds new to science, that already-known bacteria were capable of making all along. Scientists had just never triggered them in the right way.

What’s more, they found that one of the new compounds tested well as an anti-viral against respiratory syncytial virus (RSV). You’ve probably had RSV before — it’s an incredibly common source of illness that causes cold-like symptoms and can be particularly problematic for infants and the elderly.

The next steps, says Seyedsayamdost, will be twofold. They’ll crank through additional bacteria strains to see if they find even more compounds. And, of course, there’s much more to do to “explore the bioactivities of the compounds we already discovered toward potential therapeutic applications.”

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Ecology

Globe Climate: Canada’s resource reckoning is coming

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Good afternoon, and welcome to Globe Climate, a newsletter about climate change, environment and resources in Canada.

This afternoon, the Alberta government announced that it is restoring a coal mining policy it revoked last spring. At the time, the move provoked a widespread public backlash detailed by The Globe. The original decision, which opened up more than 1.4 million hectares to exploration, was made without public consultation. Premier Jason Kenney previously defended the changes.

Lots more on coal and Canada’s resources industry in this week’s newsletter edition.

Now, let’s catch you up on other news.

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Ecology

‘Incredibly destructive’: Canada’s Prairies to see devastating impact of climate change

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As the climate continues to warm at an alarming rate, experts warn if dramatic steps to mitigate global warming are not taken, the effects in Canada’s Prairie region will be devastating to the country’s agriculture sector.

According to Environment and Climate Change Canada, the country is warming, on average, about double the global rate.

Scientists with the National Oceanic and Atmospheric Administration in the U.S. recently found 2020 was earth’s second-hottest year on record, with the average land and ocean surface temperature across the globe at 0.98 of a degree C above the 20th-century average.

However, the agency found the northern hemisphere saw its hottest year on record, at 1.28 degrees C above the average.

“(In Canada) we are looking at about 6.4C degrees of warming this century, which isn’t much less than one degree per decade, which is just a terrifying rate of warming,” Darrin Qualman, the director of climate crisis policy and action at the National Farmer’s Union said.

Qualman said there is “massive change coming” to Canada’s Prairies, which will be “incredibly destructive.”

“It’s not going too far to say that if we made that happen, parts of the Prairies wouldn’t be farmable anymore,” he said.

According to the federal government, in 2018 Canada’s agriculture and agri-food system generated $143 billion, accounting for 7.4 per cent of the country’s GDP.

The sector employed 2.3 million people in 2018. The majority of the 64.2 million hectares of farmland in Canada is concentrated in the Prairies and in southern Ontario.

The effects of climate change are already being felt on the ground in the Prairies, Qualman said, adding that the NFU has already heard from farmers complaining of “challenging weather.”

“People are sharing pictures of flattened crops and buildings, et cetera, that have been damaged,” he said. “And we’re still at the beginning of this.”

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Ecology

Insect-based dog food aims to cut your pet’s carbon pawprint

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Meat has an enormous carbon footprint, with livestock liable for about 15 per cent of worldwide emissions, as we have beforehand mentioned on this e-newsletter. That is prompted specialists to suggest consuming much less meat for sustainability (and well being) causes.

However what about your pet? One research discovered that the methane and nitrous oxide emissions generated by canine and cat meals within the U.S. alone had been equal to about 64 million tonnes of CO2, or roughly the quantity produced by 13.6 million automobiles. And it might be getting worse, with a development towards feeding pets “human-grade” meat.

That is prompted some pet meals makers to look to lower-carbon protein sources — together with bugs.

Research present that producing insect-based meals requires far much less feed, land and water and generates far fewer greenhouse fuel emissions per kilogram than meats comparable to beef, pork or rooster.

That is one of many causes increasingly more pet meals containing insect protein are hitting the market. Purina, a model owned by multinational Nestlé, launched a line of canine and cat meals containing black soldier fly larvae in Switzerland in November.

In Canada, Montreal-based Wilder Harrier began promoting canine treats made with cricket protein in 2015 and pet food made with black soldier fly larvae in 2019. It plans to broaden to launch a line of insect-based cat treats later this yr and cat meals in 2022 due to “a ton of demand,” mentioned firm co-founder Philippe Poirier.

Wilder Harrier initially labored with animal nutritionists on insect-based merchandise to unravel a unique downside — specifically, the founders’ canines had allergy symptoms to frequent meats utilized in canine meals. Poirier mentioned now about half its prospects hunt down the product due to their pets’ allergy symptoms and about half for environmental causes.

Dr. Cailin Heinze, a U.S.-based veterinary nutritionist licensed by the American School of Veterinary Vitamin, has written concerning the environmental influence of pet meals. She mentioned we’re typically “not as involved as we probably ought to [be]” concerning the environmental footprint of pets.

Alternatively, she famous that the longer-term influence of newer diets, comparable to vegan meals and people containing bugs, hasn’t been nicely examined in comparison with conventional pet meals.

Maria Cattai de Godoy, an assistant professor of animal sciences on the College of Illinois who research novel proteins for pet meals (together with bugs, yeast and plant-based substances), mentioned such substances are rigorously examined to find out their security and diet earlier than being added to pet meals. 

“This can be a very extremely regulated trade,” she mentioned, however admitted it is also evolving.

Relating to bugs, she mentioned constructive information “reveals promise in direction of utilizing them increasingly more in pet meals.” Insect-based proteins have additionally earned the endorsement of the British Veterinary Affiliation, which says some insect-based meals could also be higher for pets than prime steak.

However Godoy famous that there isn’t any one-size-fits-all resolution, and pet homeowners ought to take into consideration the wants of their very own particular person pet and analysis whether or not a specific weight loss plan can be appropriate.

She mentioned that other than the kind of protein, issues like packaging and manufacturing strategies may also make a distinction. For instance, utilizing meat byproducts that may in any other case turn into waste would not drive elevated meat manufacturing the identical approach as utilizing human-grade meat.

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