New class of antibiotics discovered in soil gives hope in battle against drug-resistant pathogens

Finding new drugs to treat life-threatening antibiotic-resistant infections is critical to human health, but only one new class – teixobactin – has been discovered in the last 33 years. The World Health Organization has labeled development of such drugs a high priority and in 2015, the Obama administration released an action plan to combat antibiotic-resistant bacteria.

Scientists trawling through thousands of soil samples have discovered a whole new class of antibiotics capable of killing drug-resistant bacteria. The chemical, which has been named malacidin, appears to be non-toxic in humans and is effective in tackling several multidrug-resistant bacteria such as Meticillin-resistant Staphylococcus aureus (MRSA), raising hopes that it could be used to develop new lines of  treatment in the never-ending war against antibiotic-resistant pathogens.

Petridish with hospital superbug MRSA. SISIRAT/Shuttershock

The most effective antibiotic drugs so far have come from organisms in the environment that produce antibiotics naturally to defend against bacteria. For instance, penicillin was discovered from a fungus and vancomycin was found in bacteria that lives in dirt. Soil is a good place to look for antibiotics as it is an environment where multiple types of bacteria naturally compete for resources and use a range of exotic chemical compounds to kill each other.

“Environmental microbes are in a continuous antibiotic arms race that is likely to select for antibiotic variants capable of circumventing existing resistance mechanisms,” the authors wrote.

The malacidin chemical, identified by Dr Sean Brady and his laboratory at Rockefeller University, New York, works by attacking a fundamental step in bacterial growth, essentially interfering with a major building block that the bacteria use to build and repair their outer membrane. Initial tests showed that malacidin was not toxic to human cells, and did not induce resistance in S. aureus bacteria, even after 20 days. By comparison, bacteria in the lab have developed antibiotic resistance to the drug rifamycin in a single day.

In their study, published in the journal Nature Microbiology, the authors cautioned that it is only effective against gram-positive bacteria, species that have a very thick cell wall, and therefore, would not be effective against gram-negative bacteria. Nonetheless, the breakthrough suggests there may be more similar compounds  like malacidin yet to be discovered in our natural environment.

Research on malacidin has just begun and bringing them to pharmacies will require years of additional research and clinical trials. “The ability to tap into the world’s microbiome in a systematic way could lead to the discovery of new natural products, which historically have been the most productive source of antibiotics so far,” said Brady.

It is also a promising sign that this new class follows closely after the 2015 discovery of teixobactin. Prior to that there had been a 30-year drought, prompting dire warnings of a post-antibiotic apocalypse if bacteria continued to adapt and develop resistance to antibiotics.

 

 

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Origami-inspired artificial robot muscles can lift 1,000 times their own weight

Research into soft robotics has progressed immensely over the last decade as researchers around the world have experimented with different materials and designs, with the aim of allowing once rigid machines with limited robotic range of motion to bend, flex, and move more like living organisms than industrial hardware. However, till date, increased flexibility and dexterity had a trade-off of reduced strength, as softer materials are generally not as strong or resilient as inflexible ones, which limits their use.

All this is set to change now that researchers at the Wyss Institute at Harvard University and MIT’s Computer Science and Artificial Intelligence Laboratory (CSAIL) have created origami-inspired artificial muscles that add strength to soft robots, allowing them to lift objects that are up to 1,000 times their own weight using only air or water pressure. The study is published in Proceedings of the National Academy of Sciences (PNAS).

The study suggests that the muscles could be used to provide extraordinary strength to robots, yet allowing them to operate with precision and dexterity.

“We were very surprised by how strong the actuators [aka, “muscles”] were. We expected they’d lift a higher maximum functional weight than ordinary soft robots, but we didn’t expect a thousand-fold increase. It’s like giving these robots superpowers,” says Daniela Rus, Ph.D., Professor of Electrical Engineering and Computer Science at MIT and one of the senior authors of the paper.

“Artificial muscle-like actuators are one of the most important grand challenges in all of engineering,” adds Rob Wood, Ph.D., corresponding author of the paper and founding core faculty member of the Wyss Institute. “Now that we have created actuators with properties similar to natural muscle, we can imagine building almost any robot for almost any task.”

Each artificial muscle consists of an inner “skeleton” that can be made of various materials, such as a metal coil or a sheet of plastic folded into a certain pattern, surrounded by air or fluid and sealed inside a plastic or textile bag that serves as the “skin.” A vacuum applied to the inside of the bag initiates the muscle’s movement by causing the skin to collapse onto the skeleton, creating tension that drives the motion. Incredibly, no other power source or human input is required to direct the muscle’s movement; it is determined entirely by the shape and composition of the skeleton.

Origami-inspired artificial muscles are capable of lifting up to 1,000 times their own weight, simply by applying air or water pressure. Credit: Shuguang Li / Wyss Institute at Harvard University

“One of the key aspects of these muscles is that they’re programmable, in the sense that designing how the skeleton folds defines how the whole structure moves. You essentially get that motion for free, without the need for a control system,” says first author Shuguang Li, Ph.D., a Postdoctoral Fellow at the Wyss Institute and MIT CSAIL. This approach allows the muscles to be very compact and simple, and thus more appropriate for mobile or body-mounted systems that cannot accommodate large or heavy machinery.

“When creating robots, one always has to ask, ‘Where is the intelligence – is it in the body, or in the brain?’” says Rus. “Incorporating intelligence into the body (via specific folding patterns, in the case of our actuators) has the potential to simplify the algorithms needed to direct the robot to achieve its goal. All these actuators have the same simple on/off switch, which their bodies then translate into a broad range of motions.”

Not only can the artificial muscles move in many ways, they do so with impressive resilience. They can generate about six times more force per unit area than mammalian skeletal muscle can, and are also incredibly lightweight; a 2.6-gram muscle can lift a 3-kilogram object, which is the equivalent of a mallard duck lifting a car. Additionally, a single muscle can be constructed within ten minutes using materials that cost less than $1, making them cheap and easy to test and iterate.

These muscles can be powered by a vacuum, a feature that makes them safer than most of the other artificial muscles currently being tested. “A lot of the applications of soft robots are human-centric, so of course it’s important to think about safety,” says Daniel Vogt, M.S., co-author of the paper and Research Engineer at the Wyss Institute. “Vacuum-based muscles have a lower risk of rupture, failure, and damage, and they don’t expand when they’re operating, so you can integrate them into closer-fitting robots on the human body.”

“In addition to their muscle-like properties, these soft actuators are highly scalable. We have built them at sizes ranging from a few millimeters up to a meter, and their performance holds up across the board,” Wood says. This feature means that the muscles can be used in numerous applications at multiple scales, such as miniature surgical devices, wearable robotic exoskeletons, transformable architecture, deep-sea manipulators for research or construction, and large deployable structures for space exploration.

It seems like the robots of the future are going to be much more life-like in their appearance and range of movement than even the T-800s of Terminator fame.

PhD student discovers a way to fight drug-resistant superbugs without antibiotics

The possibility of a superbug spelling mankind’s doom, once the realm of gory science fiction, is fast becoming a horrifying reality with the rise of mankind’s worst nightmare: antibiotic-resistant superbugs.

Superbugs are bacteria or fungi that are resistant to two or more types of antibiotics, and consequently tougher to get rid off. Scientists warn that the day is not far off that one or more strains of superbugs might acquire immunity against even the most powerful of antibiotics in mankind’s arsenal. The threat is so dire that recently the United Nations declared superbugs a “fundamental threat” to global health.

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          The lethal Methicillin-resistant Staphylococcus aureus (MRSA) (Photo: Getty)

The misuse of antibiotics (such as taking them when you don’t need them or not completing a full prescribed course of antibiotic medicine) is the single leading factor contributing to this problem. The U.S. Centers for Disease Control and Prevention has released  released a list of drug-resistant bacterial and fungal infections, labeling each as “urgent,” “serious” or “concerning,” on the basis of how dangerous they are, their prevalence, and difficulty of treatment.

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                                                                               Superbugs explained

Antibiotic-resistant bacteria already kill around 700,000 people each year, but a recent study suggests that number could rise to around 10 million by 2050.

Until now, the tried and tested method to combat superbugs was to develop even more powerful antibiotics, research into which has considerably slowed down since the 1980s.

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Stagnation in antibiotic research. Image credit: Reactgroup.org

However, while scientific research continued to explore how humans could stay ahead of bacteria, interest from drug companies dwindled because antibiotics, like all other drugs, are expensive to develop.

On average, pharmaceutical companies spend $5 billion in research and testing for each new drug they bring to the market. Because about 80 percent of the drugs emerging from labs fail in safety or efficacy testing, pharmaceutical companies need to recoup billions from each new drug that makes it to the market.

Unlike antibiotic drugs, which are increasingly losing their effectiveness in the long run with the rise of superbugs, pharmaceutical companies can make greater profits on drugs that can be used regularly without losing effectiveness- such as antidepressants, statins, and anti-inflammatory medications.

It is in light of this bleak scenario that the science world was caught unawares when a 25 year old PhD student just came up with a way to fight drug-resistant superbugs- without antibiotics.

Shu Lam, a Malaysian Chinese PhD student at the University of Melbourne in Australia, has developed a star-shaped polymer that can kill six different superbug strains without antibiotics, simply by ripping apart their cell walls.

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Melbourne University PhD student Shu Lam. (Photo: Telegraph.co.uk)

“We’ve discovered that the polymers actually target the bacteria and kill it in multiple ways,” Lam told Nicola Smith from The Telegraph. “One method is by physically disrupting or breaking apart the cell wall of the bacteria. This creates a lot of stress on the bacteria and causes it to start killing itself.”

The research has been published in Nature Microbiology, and according to Smith, it’s already being hailed by scientists in the field as “a breakthrough that could change the face of modern medicine”.

“Nowadays we already see a lot of people admitted to hospital or dying from bacterial infections that used to be quite easy to treat but aren’t anymore. What I’ve discovered is a class of new antimicrobial agents. We hope that these will be replacements for antibiotics,” says Shu Lam.

She believes her method of killing bacteria using tiny star-shaped molecules, built with short chains of protein units called peptide polymers, is a ground-breaking alternative to failing antibiotics.

Lam builds the star-shaped molecules at Melbourne’s prestigious school of engineering. Each star has 16 or 32 “arms” made from peptide polymers, a process she likens to putting together small blocks of Lego.

When unleashed, the polymers attack the superbugs directly, unlike antibiotics, which create a toxic swamp that also destroys nearby healthy cells.

Not only are they really good at killing superbugs, so far they’ve been relatively non-toxic to the body.

“Well, obviously we need to do more research to assess if these molecules have any other side-effects on the body, but currently, the preliminary results are showing that they kill the bacteria but not the healthy cells of the body,” Shu says.

Is this a game-changer?

Shu’s discovery is significant because it’s an alternative to antibiotics, not a new version of the same treatment.

So far, Lam has tested her star-shaped polymers on six strains of drug-resistant bacteria in the lab, and on one superbug in live mice.

In all experiments, they’ve been able to kill their targeted bacteria – and more significantly, unlike with conventional antibiotics, generation after generation of antibiotic-resistant bacteria don’t seem to develop resistance to the polymers.

The polymers – which they call SNAPPs, or structurally nanoengineered antimicrobial peptide polymers – work by directly attacking, penetrating, and then destabilizing the cell membrane of bacteria.

Unlike antibiotics, which ‘poison’ bacteria, and can also affect healthy cells in the area, the SNAPPs that Lam has designed are so large that they can’t enter or affect healthy cells at all.

Lam hopes her “innovative” research will encourage pharmaceutical companies to invest. “I hope it will attract some interest, because what we have discovered is quite different from antibiotics,” she says.

“Some people have been telling me ‘Please work harder, so that we can have a solution and put it out on the market.’ But with research, you need to have a lot of patience because we still have quite a long way to go.”

Professor Greg Qiao, her PhD supervisor, says that Lam’s project is one of the biggest scientific breakthroughs he had seen in his 20 years at Melbourne university. But he cautions that it is still in its early stages, and will need at least another five years to develop, unless millions of pounds of investment can be found to speed the process. Cross-discipline work is still required to further reduce toxicity and work out the best way to administer the treatment, whether by tablet or injection.

Prof Qiao says: “The really good news about this is that, at the moment, if you have a superbug and you run out of antibiotics, there’s not much you can do. At least now, you can do something.”

 

 

 

Internal Combustion engine 2.0?

The quest to replace the internal combustion engine as the primary driver of road transportation has been making some serious headway since the turn of the century, driven by an industry wide push led by visionary automakers such as Tesla, and sustained efforts on the parts of governments and environmental activists  to counter the deleterious effects of climate change on our planet.

Today, electric cars having largely made the crucial cultural transition from nerd oddity to mainstream acceptance, aided by the many inherent advantages of electric motors such as over 90% energy efficiency, and instantaneous torque delivery even at 0 RPM, and the cool factor that Tesla has brought into the mix. However, the limitations of portable energy storage technology has been holding it back from completely ridding the field of internal combustion engines.

To add to what might prove to be a complete resurgence of fossil-fuel based transportation technology, an Israeli start-up firm, Aquarius Engines, claims that it has completely reinvented the internal combustion engine.

The company claims that their new engine will completely rewrite the classic design of the internal combustion engine with its multiple thrusting pistons, replacing them with a single piston that moves from side-to-side. It has fewer than 20 parts and powers the vehicle through this single side-to-side action of the solitary piston, the company said.

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Gal Fridman, co-founder of Aquarius Engines, believes the firm’s single-piston car engine had “the highest efficiency you will probably meet”.

The fewer number of moving parts and reduced engine complexity makes production much easier and less expensive. It also reduces the power demands on the engine.

Fewer parts also means less wear and tear, less chances of breakdowns, and overall improvement in the life of the engine, thereby drastically reducing cost-of-ownership.

In tests by the German engineering company FEV, the Aquarius engine’s efficiency was more than double that of traditional engines.

Such efficiency is vital as countries seek to reduce their dependence on fossil fuels for their transportation needs, the burning of which is a main cause of climate change.

“It is the highest efficiency you will probably meet,” co-founder Gal Fridman told AFP at the company’s offices near the Israeli commercial capital of Tel Aviv.

Aquarius also states that its engine has an, “exceptionally high power-to-weight/size ratio.

According to a report by AFP, Aquarius Engines is already in talks with the French auto manufacturer Peugeot to sell it their engines which are being priced at only $100 per unit.”It has the lowest emissions and the highest power-to-weight ratio.” A Peugeot spokesman said: “We are discussing with them, as with many other start-ups, without obligation or a specific project.”

For Peugeot and others, the engine could help them compete with the growing popularity of electric cars, John German, senior fellow at the International Council on Clean Transportation, said.

He said the engine would work best as part of a plug-in hybrid system, with manufacturers looking at “the idea of putting a smaller, inexpensive, range extender” alongside a battery and motor.

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Shaul Yakobi, inventor and co-founder of Aquarius Engines, poses next to the single piston Aquarius combustion engine.

The radical new design of the Aquarius engine would necessitate a stark divergence in conventional engine manufacturing techniques. It remains to be seen whether the company would be able to bring it to the market in a cost-effective manner in time to keep pace with the rapid innovations being done to eliminate the one major Achilles heel of electric car technology: limited battery capacity.

A full 120 years after internal combustion engines replaced the humble horse as the driving force for automotive transportation, the race is on. Once again.

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