Aladdin and the magic lamp: Turn the desert to find new antibiotics

Deep in Mainland China, where the Gobi desert flows into the Tibetan Plateau rises a vast expanse of rippling sand dunes and barren rocky mountains. Called the desert, but the winter here is really harsh.

Temperatures can drop below -25 degrees Celsius and rainfall is so low that only the most drought-tolerant plants and animals on the planet can survive. Yet for nearly a decade, scientists have been coming here continuously.

They toiled to flip the dunes, endure the drought and the cold of the Gobi only to find a very special life, a creature that is a treasure that can save the lives of millions of people every year around the world. gender.

In the harsher conditions, more organisms are forced to evolve and adapt to survive“, said Professor Paul Dyson, a molecular microbiologist from Swansea University School of Medicine, UK.

So, in theory, you would find in this area the most fiercely competitive bacteria for survival. To occupy the living space, water resources and meager food sources, they will secrete chemicals to destroy each other.

That’s exactly what Professor Dyson wanted when he traveled to Gobi – an antibiotic of bacteria in the barren desert that would be powerful enough to destroy the antibiotic-resistant superbugs raging around the world. .

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Remember the last time you had a scratch on your hand? And what if it gets infected? In the 21st century, a dose of antibiotics can easily solve your anxiety.

But going back more than 3,000 years from the time of Ancient Egypt all the way to the 1940s, such a scratch could eventually lead to amputation or even death if bacteria got in. blood.

Treatments for bacterial infections before people had antibiotics were basically ineffective. For thousands of years, doctors relied on a very rudimentary theory to fight bacteria.

They suggest that the symptoms of infection are due to an imbalance of four body fluids (including blood, phlegm, black bile, and yellow bile). Treating an infection therefore requires draining the blood around the wound, as quickly as possible.

Aladdin and the magic lamp Turn the desert to find new antibiotics | Living

The work can be done with cups, incision and compression of blood vessels or even the use of leeches. The scientific basis unwittingly backs this approach, which is because in the early stages of infection, some bacteria need iron to multiply and reproduce.

Because iron is transported on heme, a component of red blood cells, in theory having less blood means easier bacteria control.

It was not until after the 18th century, especially during the American Civil War (1861-1865), that the need to treat war wounds met with the development of modern medicine that led doctors to several discovery. They began to know how to use some topical drugs to treat wounds and necrosis caused by infection.

These medicines mainly contain iodine, bromine or mercury. They have the effect of inhibiting the multiplication of bacteria, but on the other hand, they are also toxic and harmful to healthy human tissues.

By the first half of the 20th century, arsphenamine, an arsenic derivative, was also added to the arsenal of bacterial infections. Although it is effective, the side effects of arsenic are terrible, ranging from rash, convulsions, fever, to kidney and optic nerve damage.

Aladdin and the magic lamp Turn the desert to find new antibiotics | Living

In general, until 1928, humans were almost always subjected to a battle against bacteria. The leading cause of death in the world then was not cancer or cardiovascular disease, but infection.

Just one strain of Streptococcus pyogenes is responsible for half of all maternal deaths and is a major cause of burn deaths. Staphylococcus aureus causes death in 80% of people with infected wounds, and tuberculosis bacteria along with pneumonia become well-known killers.

Everything changed only after August 29, 1928, when Alexander Fleming discovered penicillin – the first antibiotic for humans.

Aladdin and the magic lamp Turn the desert to find new antibiotics | Living

Alexander Fleming (1881-1955) was a Scottish physician and microbiologist. It is said that that year, when Fleming was doing experiments with Staphylococcus aureus bacteria at St Mary’s Hospital, Paddington, London, he took a vacation.

Before leaving, Fleming was lazy and forgot to wash a culture dish. Five days after he returned to the lab, Fleming suddenly found that an area of ​​bacteria in the culture dish had been destroyed.

So funny“, he thought and began to find out what happened. The results showed that in the area of ​​​​the test dish where Staphylococcus aureus was killed, there were Penicillium filaments present. Possibly spores of the fungal strain. These were hovering in the air until they landed in petri dishes and began to colonize them.

Aladdin and the magic lamp Turn the desert to find new antibiotics | Living

Penicillium secretes an antibacterial compound, later known as penicillin, which inhibits peptidoglycan on the cell wall of gram-positive bacteria. From there, penicillin penetrates the cell wall, leaking the cytoplasm and killing the bacteria.

Since human cells do not have peptidoglycan, penicillin alone has no effect on the patient itself. This mechanism of killing bacteria is therefore considered a miracle, compared to previous infection therapies.

As long as you get penicillin into the bloodstream, whether injected or orally, or even applied to the skin, you can kill the bacteria that are multiplying in your body. It is exactly like a silver bullet compared to all the other risky infection therapies.

Penicillin ushered in a golden age of antibiotics, where capsules could help with everything from simple skin infections to gonorrhea.

Aladdin and the magic lamp Turn the desert to find new antibiotics | Living

The development of antibiotics continued to be spurred by the Second World War, when the need to treat battlefield wounds led to the introduction of a wide range of new antibiotics.

It turns out that in the 20th century, finding a new antibiotic was not difficult at all. The word “antibiotics” itself means substances that an antagonistic organism produces to destroy organisms living in the same space as it.

Therefore, you can easily find antibiotics in natural environments containing bacteria. Scientists simply repeat Fleming’s experiment, growing microorganisms isolated from soil or plants in the laboratory and waiting for them to be destroyed by a natural enemy.

And because bacteria are everywhere, they simply go to the back of the garden, take some soil, put it in a culture vessel, and put it in an incubator. Heat and humidity accelerate the growth of fungi or bacteria, which secrete new antibiotic compounds, which humans then simply extract and collect.

By this simple way, scientists in the 1940s-1970s found dozens of antibiotics ranging from penicillins, cephalosporins, aminoglycosides, rifamycins, tetracyclines to glycopeptides.

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The explosion of magic pills is likened to consecutive wishes with a magic lamp. It has helped people to reverse infection, the leading cause of death in the 20th century.

As a result, from 1944-1972, the average lifespan of humans increased to 8 years. Antibiotics have become a solid pillar of medicine, underpinning the treatment of a wide range of bacterial infections, not only caused by wounds but also during surgery and childbirth.

Aladdin and the magic lamp Turn the desert to find new antibiotics | Living

The miracle of antibiotics once made people think that the miracle would last forever. “Maybe we should close the books on infectious diseases“, said William Stewart, chief surgeon general in the United States.

However, bacteria is not an easy enemy to deal with. Hundreds of millions of years before humans appeared on this planet, bacteria haveLearn how to fight the chemicals that target them.

Initially, large numbers of bacteria in a population can be killed by an antibiotic. But as long as a few bacteria in it survive, they can develop biochemical strategies to combat the drugs humans use.

Studies have shown that Four mechanisms by which bacteria do this, what they now call antibiotic resistance. The bacteria will then pass on its antibiotic resistance genes to the next generation, and from then on that strain will no longer be destroyed by antibiotics.

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Alexander Fleming himself warned of this prospect: “People who abuse penicillin today, they are responsible for the death of patients infected with bacteria resistant to penicillin later“, he said after the first commercial doses of penicillin hit the market, earning Fleming a Nobel Prize in Medicine in 1945.

That same year, penicillin-resistant bacteria emerged. But doctors and the pharmaceutical industry simply ignored that warning. They think that if a bacteria becomes resistant to penicillin, then switch to a new antibiotic.

There was basically no shortage of antibiotics in those days: Rub a magic lamp, get out in the backyard and you’ll have a new antibiotic. “Needs bacteria to be resistant to antibiotics? Choose our new drug,” was a defiant advertisement from Abbott after they discovered erythrocin in 1954.

And because antibiotics are such a profitable drug, drug companies also encourage doctors to prescribe them indiscriminately. The message sent to doctors is “Pre-order first and calculate later“Patients are given antibiotics even before the test results are available, and even when they have the flu – a viral illness where antibiotics only attack bacteria.

As a result, constantly new strains of bacteria that have adapted to antibiotics have emerged. Penicillin was introduced in 1943, but by 1945, penicillin-resistant bacteria had appeared.

Vancomycin, an antibiotic was developed in 1972, by 1988, bacteria resistant to vancomycin developed again. Similarly, Imipenem was born in 1985, by 1998, this drug was resistant.

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One of mankind’s newest antibiotics, daptomycin, was released in 2003 when doctors discovered that patients were carrying bacteria that were resistant to it in 2004. The story was repeated with ceftaroline in 2010 and bacteria resistant to ceftaroline in 2011.

Everything is likened to a sheep jumping game. When bacteria become resistant to an antibiotic, people have to find a new antibiotic. But unlike in the 1970s, when antibiotics could be easily found, the later pharmaceutical companies lost their breath in the race against bacteria.

These tiny microorganisms only take 20 minutes to reproduce and evolve, while pharmaceutical companies now need a decade to find a new antibiotic.

That’s because the antibiotics that are easiest for humans to find have been found. Like an apple tree where all the apples near the ground have been picked, we have to go higher and higher to pick the remaining apples.

More and more, the magic lamp becomes more and more sacred, the times we rub it, the god no longer appears to give humanity a new antibiotic.

Aladdin and the magic lamp Turn the desert to find new antibiotics | Living

Right at this moment, man has amassed in his arsenal about 100 antibiotics. Most of them, however, are older drugs that have been developed since the 20th century, which bacteria have had enough time to evolve to resist.

In 2000, the first American patient was confirmed by the US Centers for Disease Control and Prevention (CDC) to be resistant to all but two antibiotics. In 2008, Swedish doctors were faced with the case of an Indian patient with an infection that was resistant to all antibiotics except for one.

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The decade of 2010 was followed by a succession of patients resistant to all currently available antibiotics. In 2017, the World Health Organization (WHO) published a list of the 12 most dangerous multi-drug resistant superbugs in the world. Three of these are superbugs that are resistant to all the drugs humans have to treat them.

The prognosis of patients infected with these strains is always the worst, meaning that they can die from sepsis at any time.

According to a study published in the Lancet in January, antibiotic resistance is increasingly becoming a major nightmare for humanity. Each year, strains of superbugs directly kill more than 1.2 million people and indirectly kill another 4.95 million.

New data from our study reveal the true scale of drug resistance worldwide.”said Chris Murray, a health economist at the University of Washington who authored the study published in The Lancet.

Right now, antibiotic resistance has killed more people than the HIV/AIDS pandemic and the cold sores combined. “Previous estimates have predicted that by 2050, there will be about 10 million deaths annually due to antibiotic resistance. But now we know for sure that we are closer to that number than we ever thought“, said Murray.

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Ignoring the numbers, you can also tell if the nightmare has come to you if you have ever had an infection. In the past, a respiratory infection such as a sore throat or a urinary tract infection could be completely cured with a short course of antibiotics. Now, you always have to take a combination of two to three antibiotics to treat it.

Children born after the year 2000 are at risk of being in the 25% group of children with UTIs that require three different antibiotics. The remaining 25% must be treated with 2 drugs and only half of the children can be cured with a single drug.

The loss of effectiveness of antibiotics is pushing people back to the time before the magic pills were born. It is a post-antibiotic era, scientists warn, where a pillar of medicine is collapsing.

We will lose all defenses for people with weak immune systems. They include cancer patients, people living with HIV, premature babies… This means the death of all these people.

Next, the human surgical technique was disabled. Many surgeries require the use of prophylactic antibiotics. When antibiotics lost their effectiveness, the hospital’s operating room was like no roof.

We will not be able to operate on hearts, transplant kidneys, give catheters to stroke patients… Doctors cannot operate even simply to correct the knee joint. Caesarean section is not possible, and even in the most modern hospitals, 1 in 100 women will die.

Aladdin and the magic lamp Turn the desert to find new antibiotics | Living

Infection causes fear from trivial diseases. Strep throat causes heart failure. Pneumonia kills 3 in 10 children with the disease. Skin infections mean amputation surgery.

Then what else do you dare to do when any injury can kill people. Do you dare to ride a motorbike, roller-skate, climb ladders to fix the roof or let your children play as they please in the park, where they can trip and scratch their heads at any moment?

Aladdin and the magic lamp Turn the desert to find new antibiotics | Living

The failure of antibiotics has even led many scientists to think that they should look for a new way to treat infections. Which is actually old, methods such as phage – using viruses to infect and kill bacteria – are just a way of treating infections in a renewed pre-antibiotic age.

Some really modern approaches involve making gold nanorobots, capable of finding and killing viruses in the blood. However, all of these methods are very complicated, requiring patients to stay in the hospital and be monitored for a long time. On top of that, they’re still in beta.

An old recipe, “old but gold“It’s still about finding a new antibiotic to replace the antibiotics that have lost their effectiveness, and from now on use it carefully. Because after all, nothing is simpler than a chemical packaged in a container. a capsule, which you can take home and take to control the bacteria in your body.

However, finding a new antibiotic in the 21st century is no longer a simple task. Friend Remember the example of apples? When its fallen and low-growing fruits have been picked, sweet fruit is only found in high places and dangerous places.

Aladdin and the magic lamp Turn the desert to find new antibiotics | Living

The discovery of a new antibiotic has gone from being simple, when a scientist just takes a handful of soil in their backyard, to having to travel to the most remote and inhospitable places on the planet, where there are organisms that secrete compounds against bacteria to which they are not yet resistant.

Paul Dyson and his colleagues at the Chinese Academy of Sciences began that journey in 2013. In an area called the Alxa Plateau located at the southernmost tip of the Gobi Desert, they found a completely new bacterium of the genus Streptomyces.

Streptomyces is a genus that includes more than 500 known species of bacteria. They are found in abundance in the soil, so much so that the molecules produced by Streptomyces are what give the soil its distinctive scent.

But more importantly, Streptomyces is an extremely important source of biomedical bacteria. More than two-thirds of the natural antibiotics used in clinical practice today are derived from this genus of bacteria, which are compounds that they secrete to kill other strains of bacteria competing for space. in nature.

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However, the fact that a strain of bacteria secretes an antibiotic does not mean it can be exploited in practice. Like a chemical factory, bacteria also have to pass productivity and output tests.

Laura Piddock, scientific director of the Global Antibiotic Research & Development Partnership (GARDP) in Geneva, Switzerland said:Research on new antibiotics is often hampered by low yields. Plus, sometimes bacteria have the potential to make useful substances, but their genetic machinery is turned off so no antibiotics are made.”

However, the new strain of Streptomyces that Professor Dyson found in the Gobi Desert is different, it can both secrete an antibiotic and can guarantee the production of that chemical. The secret lies in a molecule of this bacterium’s tRNA.

tRNAs are transport RNA molecules, which allow organisms to read their genetic material and, by doing so, build other molecules they need to survive.

Sequencing the genome of Streptomyces, the scientists found that its tRNA is capable of turning on a molecular switch that controls the amount of antibiotics the strain produces. From there, Streptomyces in the Gobi desert can increase antibiotic production much more effectively than other antibiotic-secreting bacteria.

Aladdin and the magic lamp Turn the desert to find new antibiotics | Living

Knowing this, Professor Dyson and his colleagues came up with an idea. They wanted to take the tRNA gene from Streptomyces bacteria found in the Gobi desert and transplant it to other strains of Streptomyces bacteria.

The team’s hypothesis was that genes from fast-growing bacteria would boost antibiotic production for these older bacteria. And that’s exactly what happened. When Streptomyces Gobi tRNAs were transferred to common Streptomyces, they produced antibiotic compounds within 2-3 days.

The time period is shortened to only half that of other common Streptomyces species. Streptomyces tRNA found in the Gobi desert is like a new wish for a magic lamp.

Because from now on, if scientists find a new type of bacteria that can secrete antibiotics but don’t make the usual dose, they now have a tool to boost their productivity. and turn that bacteria into a new source of antibiotics.

Aladdin and the magic lamp Turn the desert to find new antibiotics | Living

“I really believe this is a very simple strategy, and it can be integrated into any new antibiotic discovery program.”said Professor Dyson.

Piddock agrees. She says catching bacteria produces large amounts of antibiotics.”This is something that is of great interest to researchers in this field.” “This will allow them to discover new antibiotics, drugs that can lay the groundwork for a new era in the treatment of diseases. treat infections”.

Aladdin and the magic lamp Turn the desert to find new antibiotics | Living

The Gobi Desert is just one of the nooks and crannies of the planet, where scientists are looking to explore life in the most extreme places. In addition, they also dive into the deep sea, find the craters, glaciers, and even the coldest highlands in Ireland …

In these habitats, temperature, pH, pressure and even salinity are always at one end of the spectrum. The bacteria living in isolation there have to compete more fiercely, leading to the stronger antibiotic compounds they secrete.

Scientists hope that there will exist ways to help people get out of the current antibiotic resistance crisis.

A few years ago, Professor Dyson also participated in an expedition to the Boho Highlands in Northern Ireland. The site is famous for its high biodiversity, in an environment as harsh as the Gobi Desert.

Aladdin and the magic lamp Turn the desert to find new antibiotics | Living

Boho has limestone areas interspersed with acid marshes, patched with alkaline grasslands. The changing landscape constantly challenges the bacteria here to become hardy and strong.

For centuries, villages occupied by the Druids 1,500 years ago were rumored to be a mystical land, home to sacred soils with healing powers.

There are always such legends, about local healers who have a precious remedy. They just passed that remedy on to their children, from generation to generation with very strict laws“, said Gerry Quinn, a scientist on the team who used to live in Boho.

You must not sell that remedy to anyone, you must not use it to cheat, you must apply it according to what you have been taught.”

There was an old man in Quinn’s family who worked as a healer himself. He is known for his ability to cure many infections. Recalling that story, Quinn went back to his hometown to collect microorganisms that lived in the soil.

With the help of Professor Dyson, he found strains of bacteria named Streptomyces sp. Myrophorea. These soil bacteria in Boho are secreting powerful antibiotics that can fight four of the top six drug-resistant pathogens on the WHO list, including staph MRSA.

Aladdin and the magic lamp Turn the desert to find new antibiotics | Living

However, it is important to note that the newly discovered bacteria are only the first of many further steps that need to be taken to help people acquire new antibiotics.

Very few of these new findings make it to the final stage, passing clinical trials into treatment. One of the barriers, as studies have shown, is that the amount of antibiotics that bacteria can produce is too low.

Now, Professor Dyson hopes that with the new tRNA gene he has discovered in Streptomyces bacteria in Gobi, it will be a solution to the problem. If tRNA could be transplanted to any bacteria, it would restart searches in the home garden, opening the door for older strains of bacteria to release more powerful antibiotics.

Streptomyces’ tRNA could then become a gift of the desert, a new wish from the genie to help humanity once again overcome the antibiotic crisis. It’s clearly a promising future, and there’s much to look forward to from these scientific journeys into the desert.

Refer Wired, Theconversation, Nature, SciencealertOpenmind, Mosaic

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