Are there antibiotics for all bacteria somewhere in the earth?

Are there antibiotics for all bacteria somewhere in the earth?

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When I read about Penicillin, I found that it came from a green mold to protect itself.

If all bacteria and/or molds in competition to survive, can we believe that there is an antibiotic for each bacterium somewhere in the earth?

In other words, just like bad bacteria change themselves to resist against the existing antibiotics, could good bacteria/molds produce antibiotics against the bad bacteria?

If so, can we use them like Penicillin, or should we still develop most of them?

The number of antibiotics that remain undiscovered is huge, but is estimated to be tens of thousands of compounds.

The number of bacteria that remain undiscovered is also huge, but is estimated to be perhaps millions of species.

Resistance to antibiotics is developed by bacteria in response to other bacteria and human antibiotic use, but in theory all antibiotics should work on previously unexposed bacteria. In practice there are resistance mechanisms that operate on whole classes of antibiotics at once(drug exporters, for instance). So there might be a bacterium that happens to be actively or passively resistant to every antibiotic on the planet, but it's a question of statistics. I think it's pretty unlikely but there are a lot of bacteria, so it's theoretically possible. (It wouldn't be a dangerous pathogen, that amount of drug-resistance genes would 'weigh down' the genome and make it slow to divide, and all those transporters would be great immune system targets. The human immune system would eat it for breakfast.)

What is true is for every bacteria, there are at least some antibiotics it's already resistant to. Furthermore, some antibiotics aren't useful because they aren't selective enough and they are simply poisons. (We use them for chemotherapy agents sometimes, but they're not useful antibiotics).

Some fun examples: Vancomycin-resistant S. aureus is completely immune to nearly every antibiotic, including the last line of defense(methicillin) and the toxic really really last line of defense (vancomycin). It's susceptible to trimethoprim-sulfamethoxazole, one of the oldest antibiotics out there(~80 years old). On the other hand, the organism that causes tularemia is naturally immune to trimethoprim-sulfamethoxazole and always has been. It, in turn, is susceptible to nearly all other antibiotics.

Tiny Earth: Advancing antibiotic discoveries through undergraduate research 1

More and more bacteria are becoming resistant to traditional antibiotics, and this resistance has become a focal point of research at many universities. Common infections like pneumonia, tuberculosis and salmonellosis are becoming harder to treat with today’s antibiotic medicines – creating an urgent need for new antibiotics.

Tiny Earth was launched in June of 2018 to address this problem. Jo Handelsman created the program at Yale University and soon brought it to the University of Wisconsin–Madison when she returned to direct the Wisconsin Institute for Discovery.

“The program’s goals are intertwined because it is participating in addressing a global health problem that is so inspiring to the students,” says Handelsman.

The mission of Tiny Earth is twofold: to address the antibiotic crisis and to counter the shortage of professionals in science, technology, engineering and math, or STEM, disciplines. To accomplish this, the initiative offers a class to undergraduate students that allows them to gain substantial laboratory experience while exploring their scientific interests.

“Not only are students learning scientific research practices, they’re also actually working toward solving a major health crisis,” says Josh Pultorak, WID researcher and instructor for the undergraduate Tiny Earth course. “Recruiting students to focus on the issue is a way to collect a lot more data useful for compound discovery while also being educationally beneficial.”

In the course at UW-Madison, students are encouraged to develop their own ideas for finding which variables influence antibiotic production in bacteria. The students form small groups and choose a variable to study. One group in this semester’s class decided to manipulate the temperature at which the bacteria are cultured, while others introduced stimuli like caffeine to investigate how bacteria react.

One student group decided to manipulate the temperature in which the bacteria were cultured. Photo by Tyler Fox.

At each biweekly meeting, the students return to their bacterial cultures and note any new developments. Their findings will be combined into their final research paper and poster report, which is displayed at the Introductory Biology research symposium at the end of the semester.

The course, which is offered and supported by the Departments of Integrative Biology and Plant Pathology under Professor Doug Rouse, is composed of freshmen and sophomores, and it satisfies their Independent Project requirement for Introductory Biology (Bio 152). For many of the students, the class presents a unique opportunity to explore their interests in research and the medical field early in their college path.

“It’s a great foot in the door for medical school, and it’d be cool to make a notable finding while in this class,” says Alec Brenner, a sophomore in the spring semester class.

Many of the students were enthusiastic about how the class is arranged, sharing their excitement about the chance to choose their own area to focus on and gain hands-on experience in that topic. This type of instruction, referred to as Course-based Undergraduate Research Experiences (CUREs), has proven to be more effective for teaching science than traditional lectures.

“Rather than sitting and listening passively to a lecturer, the students are actively participating and having opportunities to try new things, fail and try again,” says Pultorak. “The students are getting more comfortable learning around their peers and asking questions.”

Josh Pultorak, instructor for the course, is a WID researcher and thoroughly enjoys teaching students critical thinking and laboratory skills. Photo by Emma Byers.

Pultorak adds that the CURE model has been successful in encouraging students to pursue additional research opportunities and careers after they complete their coursework.

“I’m hoping this class can propel me into more research on campus,” says Jessica Dable, a sophomore. “I’m on the pre-health track, and the skills I’m learning are diverse and applicable to many other areas of science.”

Ultimately, the exploratory research of the students contributes reams of data to the Tiny Earth project, and the students gain valuable lab experience which they can take into their future careers as scientists and STEM professionals.

“All the institutions that are implementing Tiny Earth are doing antibiotic discovery research, but here at UW–Madison, we’re taking it one step further in that the students are asking research questions and making their own discoveries,” says Pultorak. “And there’s a growing number of students that have completed the course and reported that they really enjoyed it, so we’re seeing some pretty positive word-of-mouth feedback too.”

Header photo by Kim Leadholm.

Show/hide words to know

Antibiotic: a substance that weakens or destroys bacteria.

Penicillin: one of the first antibiotics, medicine that kills bacteria. more

Petri dish: a small round dish that scientists use to grow bacteria.

Receptor: a molecule on the surface of a cell that responds to specific molecules and receives chemical signals sent by other cells.

Resistance: to withstand the force or effect of something for example, the ability to protect against parasites by killing or limiting the growth of the parasite.

A new antibiotic to combat drug-resistant bacteria is in sight

More and more bacterial pathogens of infectious diseases become resistant to customary antibiotics. Typical hospital germs such as Escherichia coli and Klebsiella pneumoniae have become resistant to the most -- and in some cases even all -- currently available antibiotics. Their additional external membrane makes these bacteria difficult to attack. It protects the bacteria particularly well by preventing many substances from getting into the cell interior. Especially for the treatment of diseases caused by these so-called gram negative bacteria, there is a lack of new active substances. An international team of researchers, with the participation of scientists from Justus Liebig University Giessen (JLU), has now discovered a novel peptide, that attacks gram negative bacteria at a previously unknown site of action.

"Since the 1960s scientists have not succeeded in developing a new class of antibiotics effective against gram negative bacteria, but this could now be possible with the help of this peptide," said Prof. Till Schäberle from the Institute of Insect Biotechnology at JLU and project leader at the DZIF. His research group is involved in the discovery. The researchers use a screening, a classical approach from the natural product research. Thereby the team of Prof. Kim Lewis, Northeastern University in Boston, Massachusetts (USA), tested extracts of bacterial symbionts of insect-pathogenic nematodes to verify the activity against E. coli. Thus, the researchers were able to isolate a peptide that they have called Darobactin.

Darobactin consists of seven amino acids and shows structural characteristics. Several amino acids are linked via unusual ring closures. The substance shows no cell toxicity -- a prerequisite for the use as an antibiotic. "We have already been able to gain insights about how the bacteria synthesize this molecule," said Prof. Schäberle. "Currently we are working in the field of natural product research at the Institute of Insect Biotechnology of the JLU to increase the production of this substance and to generate analogues."

The researchers also determined the site of action of Darobactin. They found that Darobactin binds to the BamA protein, located in the external membrane of gram negative bacteria. As a result, the establishment of a functional external membrane is disrupted and the bacteria die off. "It is particularly interesting to note that this previously unknown weak point is located on the outside of the bacteria where substances can easily reach it," explains Prof. Schäberle.

Darobactin exhibited an excellent effect in the case of infections with both wild-type, as well as antibiotic-resistant Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae strains. Thus, Darobactin presents a very promising lead substance for the development of a new antibiotic. The urgency of this matter is also emphasised by the fact that the World Health Organisation (WHO) has attributed the necessity of research and development against resistant pathogens the highest priority for human health.

As more bacteria grow resistant to antibiotics, scientists are fighting back

Scottish bacteriologist Alexander Fleming's discovery of penicillin, the world's first antibiotic, saved countless lives. But even as the bacteria killer first hit the U.S. market—in the closing months of World War II—Fleming warned the world about what penicillin might unleash.

Misuse of the antibiotic could result in an explosion of resistant bacteria, he cautioned in his 1945 Nobel Prize speech. His words proved prophetic.

Today, less than 100 years after their debut, antibiotics are losing the war against germs. Antibiotics are meant to quash bacteria and certain fungi, but superbugs have evolved to survive them. Germs built their potent defenses thanks in large part to the overuse of antibiotics in humans and animals. In this new era, these drugs have rapidly become less effective at fighting infection.

"We did not recognize how quickly we could lose what we have in our toolbox," says Neha Nanda, medical director of infection prevention and antimicrobial stewardship at Keck Medicine of USC. "We know the history. Why are we letting history repeat itself in a way that will harm us today?"

The Centers for Disease Control and Prevention (CDC) calls antibiotic resistance "one of the biggest public health challenges of our time." Each year, about 2.8 million people in the U.S. are infected with antibiotic-resistant bacteria or fungi. More than 35,000 of them die, among an estimated 700,000 deaths worldwide.

At USC, scientists are working to build new lines of defense against the rise of powerful bacteria and fungi. They've turned the university into an epicenter for research as they race to develop new strategies and tools to counteract the growing threat.

How Does Antibiotic Resistance Occur? A Prescription for Trouble

"Antibiotic resistance is a naturally occurring phenomenon—it's been happening before we humans walked the earth. We're just making it worse," says Adam Smith, an environmental engineer at the USC Viterbi School of Engineering who studies the presence of antibiotic-resistant bacteria in our water supply. Microbes have gained such resilience through adaptation, he adds, that "we're quickly reaching a post-antibiotic world."

Used properly, antibiotics can knock out many bacterial infections, from strep throat to urinary tract infections. But the CDC estimates that at least 30% of antibiotic prescriptions in emergency rooms, hospitals and clinics are inappropriate. They're doled out for virus-caused health issues they can't fix, such as the flu or a common cold.

Says Nanda: "What's disappointing is why this has happened—the absence of a disciplined restriction around prescribing antibiotics."

If you take an antibiotic for the flu, the drug won't touch the virus. But it will destroy other bystanders, like good bacteria that digest food, keep us healthy and attack infection. Any surviving germs left in your body get tougher. These survivors multiply and swap their drug-resistant genes like trading cards. The more patients take antibiotics, the more this can happen.

Because antibiotics are used so often in hospitals, and because bacteria thrive in such settings, these facilities can sometimes harbor resistant germs.

That means chronically ill and immunocompromised people, who are more likely to need intense medical care, are at especially high risk. Increasingly, doctors are forced to tell their hospitalized patients there is no antibiotic to treat them or "they're down to a drug of last resort," Nanda says.

Adding to the challenge is that prescribing an antibiotic has become what Nanda calls "a social act." Physicians want to help patients—"to do something," she says—and patients often insist on an antibiotic prescription when they feel sick.

Jason Doctor, an expert in physician behavior and psychology at the USC Price School of Public Policy, calls prescribing antibiotic drugs a gray area because it's so often a judgment call. The best course of action to treat a patient may be unclear, he says, which can open the door to physician overprescribing.

A 2019 national survey by Doctor and other researchers illuminates the challenge. It found that 91% of primary care physicians believe inappropriate antibiotic prescribing is an issue in outpatient settings, but only 37% agree it takes place in their practice. "Clinicians recognize there is a problem," he says, "but they don't see that they're responsible for it."

Much of his research focuses on how to persuade physicians to reduce antibiotic prescribing. One strategy that works: Giving them a performance goal. If you show physicians that their colleagues hit a benchmark for writing fewer inappropriate prescriptions, Doctor says, "they want to change their behaviors to emulate their peers."

The Bacterial Baddies at the Heart of Antibiotic Resistance

Who are the supervillains of the superbug universe? Gram-negative bacteria. They block infection-fighting white blood cells and drugs with their protective outer capsule. Examples of these bad bugs include Escherichia coli (commonly known as E. coli), guilty of causing respiratory infections, diarrhea and more, as well as Salmonella and its food-borne illnesses.

Don't forget the fungi. Charles McKenna, director of the Center for Drug Discovery at the USC Dornsife College of Letters, Arts and Sciences, has been on a global hunt for new approaches to antifungal treatments. Currently on his radar is the aggressive yeast-like fungus Candida auris. This emerging threat causes blood, wound and ear infections, and it repels most antibiotics, he says. "It potentially could resist all of them, and we'd be out of options."

As McKenna explains, superbugs got their name because they're indifferent to many drugs. "If we had decent drugs, they wouldn't be superbugs anymore—they'd be out of business," he says. The solution is to improve drug discovery.

The drug discovery process worldwide is too slow and costly, he says, and "viruses and bacteria can mutate more rapidly than we can make a new drug." It takes 10 years or more to develop and approve a new antibiotic. But McKenna is hopeful. If his predictions prove true, artificial intelligence will soon accelerate the discovery of new medicines. Robots aren't finding germ-killing drugs yet, but he sees them on the horizon.

As McKenna looks to the future, microbiologist Brian Luna looks to the past in his quest against a life-threatening supervillain: Acinetobacter baumannii. Strains of this highly drug-resistant bacteria typically infect vulnerable patients in hospitals.

Along with his colleagues at the Keck School of Medicine of USC and other institutions, Luna scoured 12,000 drugs already approved for other conditions to see if one might work against A. baumannii. The USC team found an answer among the classics: rifabutin, a drug discovered in 1975 and originally used to treat tuberculosis.

Now the researchers look to recruit other old antibiotics to perform new duties. "It's always going to be an uphill battle," Luna says. "Bacteria have had an evolutionary head start of several millions of years."

Environmental Pressures Play Key Role in Resistant Bacteria

Hospitals and clinics aren't the only home turf for superbugs. In the U.S., about 70% of all antibiotics deemed "medically important"—drugs that can be used to treat human disease—are sold for use in livestock. Farmers and veterinarians rely on them not just to treat sick cows, pigs and chickens, but also to prevent disease in healthy animals (a practice largely banned in California).

The CDC estimates 20% of antibiotic-resistant infections in humans annually are linked to agriculture. When people eat chicken and steak, they also might be eating drug-resistant bacteria if the food is tainted from poor processing or preparation during its farm-to-fork journey. But Marlène Maeusli, a Ph.D. candidate at the Keck School of Medicine, warns: "You can't think, 'I'm a vegetarian, so I'm safe.' Superbugs are everyone's responsibility—and risk."

Maeusli led a recent study that showed how eating plants carries its own dangers. The researchers exposed lab-grown lettuce to E. coli, then fed the lettuce to mice and tracked the resistant bacteria as it colonized the rodents' intestines.

In fields far outside the lab, animal manure used in fertilizer for crops can seep into irrigation water—and this contaminated water spreads bacteria onto plants. "Our findings highlight the importance of tackling foodborne antibiotic resistance from a complete food-chain perspective," Maeusli says.

That food chain includes water, says Smith, the water quality researcher from USC Viterbi. He and other USC researchers have found evidence of bacteria becoming genetically resistant to antibiotics in wastewater treatment plants, where water is recycled for irrigation, car washes, firefighting and even drinking. Bits of DNA that make microbes resistant can then get into groundwater, where other bacteria can pick them up and grow stronger.

A concerned Smith thinks solutions need to come from two directions: Engineers have to come up with answers to protect the water supply, whereas health care pros need to safeguard against the spread of bacteria and inappropriate antibiotic use.

To Stop Antibiotic Resistance, Experts Keep a Closer Watch

The World Health Organization and others have called on hospitals and medical centers to adopt antimicrobial stewardship programs that promote appropriate use of the drugs and improve patient outcomes.

At USC, Nanda and a cross-disciplinary team monitor antibiotic use in the Keck Medicine hospital system. Some antibiotics can only be prescribed by Keck Medicine's infectious disease specialists, whereas others get special scrutiny once administered. Though Nanda sees progress, "changing behaviors doesn't happen overnight."

In the meantime, she wants medical science to explore alternative bacteria fighters, including advanced immunotherapies. Scientists are investigating the powers of bacteriophages, which are viruses that specialize in infecting and destroying bacteria. Chemists and engineers have their eyes on antimicrobial polymers that can kill drug-resistant bacteria in minutes, along with nanoparticles that selectively target certain bacteria.

The public has a role in prevention, too. Practice good hygiene. Demand healthier food practices. Avoid antibiotic overuse and get vaccinated. "Everyone can be their own best advocate," Nanda says. "Help create a culture of accountability and awareness."

Researchers have found bacteria with antibiotic resistance genes in Antarctic environments untouched by humans.

Antibiotic resistance is a major public health crisis worldwide as bacteria develop the ability to defend themselves against many, sometimes all, of the antibiotics we have at our disposal. Infections caused by these bacteria are often life-threatening. In order to continue fighting these infections, we have to figure out how antibiotic resistance develops, evolves, and spreads.

Many people think that antibiotic resistance developed from the irresponsible use of antibiotics for illnesses like colds or the flu (antibiotics can not cure a viral infection), and that’s not wrong. We do have a huge part to play in the rise of the “superbug,” another name for antibiotic-resistant bacteria, but human antibiotic use is not the reason bacteria started becoming resistant to antibiotics.

It turns out they always have been.

Many microorganisms have been producing antibiotics for millions (potentially billions) of years. Antibiotics serve many purposes in nature and where there are antibiotics, there is antibiotic resistance.

All of the drugs we have currently are either natural products or derived from natural products, meaning that the genes encoding resistance to these drugs probably already exist somewhere. Bacteria can also mutate their genes when they are under stress in order to make new resistance genes that help them survive when antibiotics are present. Whether they already had a resistance gene or just developed it, they can share those genes with other bacteria in the population, through a process called horizontal gene transfer.

Knowing what resistance genes are already present in the environment is an important part of predicting how bacterial communities might react to the antibiotics we dump into the environment. This knowledge is crucial for planning out how to deal with infections and prevent outbreaks.

One of the best ways to figure out which antibiotic resistance genes are present in an environment that has not been influenced by humans is to study one, which is exactly what a group of researchers at the University of Pretoria, South Africa, did.

Researchers took soil samples from 17 sites in Antarctica that had no known exposure to human usage of antibiotics. They looked at the genes present in the samples using a process called “shotgun metagenomics,” in which DNA is extracted from environmental samples (in this case, from Antarctic soils). These bits of DNA are analyzed to reconstruct the genes carried by each species in the sampl e. For the first time in a pristine environment, the group used this method to describe the group of resistance genes, called the “resistome,” and identified the different bacteria present in each sample.

Across their 17 sites, researchers found 177 antibiotic resistance genes representing all of the known types of bacterial antibiotic resistance. They also found that the bacteria carrying the most resistance genes also carried genes for the production of the antibiotics they were resistant to, and these bacteria were found in less diverse populations. This means that bacteria could be actively using the production of antibiotics in the soil for a competitive advantage. The researchers also argue that the ancestral bacteria probably obtained their antibiotic resistance through horizontal gene transfer, but that the modern bacteria inherited it directly from their parent cells.

These findings are important because antibiotics end up in the environment through our trash, our agriculture, and our wastewater. This generates new genes and stimulates the transfer of old and new genes within microbial communities. Gene sharing produces an environmental “resistome,” a collection of resistance genes that many bacteria can use. Studying this resistome could help scientists inform doctors of what to expect in the clinic and help policy makers create effective strategies for combating infections caused by antibiotic-resistant bacteria.

Inside the slimy underground hunt for humanity's antibiotic saviour

The first time Naowarat Cheeptham ventured down into the Iron Curtain Cave, one day in 2011, the darkness was all-consuming. Turning away from the steel ladder – the only route back to the small square of sunlight far overhead – the biologist forced herself to continue forward.

Cheeptham, 48, who is known by her friends as Ann, did not stumble upon the Iron Curtain herself. The cave, located in the hills of Chilliwack, in British Columbia, Canada, were discovered in 1993 by Rob Wall, a local construction contractor and amateur caver. Wall was exploring the hills in search of uncharted caverns he might open up and explore for his own pleasure. A great deal of caves in this area of Canada are actually closed sinkholes. As such, Wall’s search involved a process called, unsurprisingly, digging, in which promising, sunken areas of ground are excavated. One day, Wall was walking through the woods and tripped into such a hole. He returned the next day with a friend and a shovel. The pair dug for three hours, uncovering a hole ten metres deep, with two small rooms at the bottom. It was everything Wall had been looking for.

It wasn’t until six months later, in the autumn of 1993, when Wall was showing off his discovery to a group of friends, that one of them noticed a breeze blowing through from the back of the cave. The group investigated, shifting rocks until they opened up an entrance to half a kilometre of pristine caves. The underground network shone with gypsum crystal, the walls and floor bristling with stalagmites and stalactites. Not human being had been there before. “It was beautiful,” Wall says.

Wall was approached by Cheeptham in 2011. The biologist was on the lookout for local caves to explore and Wall invited her to give a presentation to the Chilliwack River Valley Cavers (CRVC), explaining her project. Cheeptham explained that the dark, dank subterranean caves are teeming with life in the form of largely uncharted extremophiles – organisms that thrive in conditions that would be geochemically hostile to most life forms on earth. For Cheeptham and her colleagues from Thompson Rivers University Department of Biological Sciences, spelunking in search of these extremophiles is no mere hobby, but a last-ditch attempt to find a solution to one of the biggest global threats facing humanity today: antibiotic resistance.

While extremophiles are not the only avenue in the search for new antibiotics, their ability to not only survive but thrive in habitats where other bacteria would die suggests their chemical secretions are particularly potent. Caves are a rich source of less-studied bacteria because of their natural biodiversity, and seclusion from other environments in which bacteria usually develop.

It is not actually the bacteria themselves that are used to make antibiotics, but their metabolites – chemical compounds produced by them as a by-product of their growth. Yeast’s metabolite, for example, is the result of fermentation. It was once thought that some of these metabolites existed to kill off competing bacteria. However, new thinking popularised by a number of biologists, including Julian Davies at the University of British Columbia, argues that the true function of such metabolites in nature may be to act as a form of language between bacteria, enabling them to communicate and actually share resources. In a cave, this is particularly vital. After all, as Cheeptham points out, “[In a cave habitat] is it better for them all to compete and die, or to live together in co-operation?”

After watching Cheeptham’s presentation, local caver Doug Storozynski, 51, volunteered to help her explore the local caves. While not as technically challenging as other caves in the vicinity, the Iron Curtain still contains its share of tight squeezes, and requires an experienced guide to navigate safely. When they descended into the gloom, Cheeptham felt, at first, claustrophobic and scared. But as she and her team ventured deeper through cramped crawl spaces, numbing underground waterways and abrasive rock walls, their way lit by head-torches, the cave came alive. Stalactites hung from the ceilings, stalagmites rising from the ancient floor.

Bacteria inhabit secondary mineral deposits in the form of soda-straw speleothems – natural calcium-based deposits which include stalactites and stalagmites. After 15 minutes of feeling their way along in the near-dark, Cheeptham and her team reached the back wall of the cave, where a cascade of red-tinged, curtain-like limescale deposits give the cave its name. Next to this wall, the ceiling sloped down into the darkness of a side recess. It was the 60-centimetre stalagmites hanging from this ceiling that Cheeptham targeted. As the blue-grey caverns took shape, Cheeptham’s trepidation was replaced by curiosity and excitement.

Crawling into position, she knelt in the small space between floor and stalagmite and retrieved the sample kit from her rucksack. With sterile forceps she scraped away a near-minuscule section from the tip of the first stalagmite, dropping it into a 50ml Falcon Tube before securing it away. She worked quickly by the light of her head torch, filling her half-dozen containers with stalagmite samples. The team then retraced their steps back to the surface. Cheeptham deposited the samples in the coolbag designed to keep the bacteria alive until they could be analysed in her lab.

Around the world, everyday surgical procedures, from treatments for common infections to chemotherapy, rely on antibiotics. In the past decade, however, the drugs we rely on to keep us safe from everything from E. coli to severe acute respiratory syndrome (SARS) are failing to keep up with the rapid evolution of such infections and viruses. As these antibiotics continue to lose their efficacy, we lose our ability to treat even the most basic of illnesses. The situation is so severe that the World Health Organization regards antibiotic resistance as “one of the biggest threats to global health, food security and development today”.

Nor is this a new crisis. In 2014, the Prime Minister David Cameron appointed economist Jim O’Neill to investigate the economic fallout of antibiotic resistance. The resulting report, the Review on Antimicrobial Resistance, put the global annual death toll due to drug-resistant superbugs at 700,000, with an estimated annual mortality rate of ten million by 2050. O’Neill also predicted that, should the crisis continue without a satisfactory response, the reduction in worldwide population would diminish the global economic output by up to 3.5 per cent, at a cost of $100 trillion (£63tn) – roughly 35 times the GDP of the UK. Four years later, we’re no closer to solving the problem.

As of April 2018, a new strain of typhoid – resistant to five different antibiotics – has killed four people in Pakistan and affecting the health of more than 800 others. Also this year, Public Health England reported the “worst ever” case of Neisseria gonorrhoeae, after UK instances of the infection rocketed from just under 15,000 in 2008 to 41,000 in 2015. Even the antibiotic colistin – often administered as the final treatment when all other antibiotics have failed – is losing its effectiveness. A 2017 summit of the American Society for Microbiology reported that bacteria possessing the colistin-resistant mcr-1 gene has now spread around the world. In April 2018, in response to this dire prognosis, Rumina Hasan, a pathology professor at Pakistan’s Aga Khan University, told The New York Times that “Antibiotic resistance is a threat to all of modern medicine — and the scary part is, we’re out of options.”

Contrary to common misconception, human beings have not developed a resistance to antibiotics through overexposure. Instead, the bacteria themselves have evolved to evade our methods of killing them. We have, according to Cheeptham, around 1.3 kilograms of bacteria in and on our bodies at any one time. Their mass is roughly the equivalent to that of the human brain and, despite what domestic kitchen cleaners and soaps would have you believe, 99.9 per cent of all bacteria are actually neutral or beneficial to our health.

“Previously, we thought that overuse and misuse of commercially available antibiotics caused resistance in bacteria,” Cheeptham explains. “But the truth is that we train them. When bacteria see triclosan [an antibacterial agent found in cleaning products, soap and toothpaste] coming towards them, they want to live, like all life on Earth. Most will die, but some figure out defence mechanisms that help them survive, such as creating a pore in their cell wall to allow them to pump out the drug faster than it comes in.” She taps her finger on the table to emphasis a point that she is clearly still in awe of. “Bacteria are smarter than us.”

This isn’t the only revelation that has changed the way researchers look at bacteria. “We’ve known since 1928 that bacteria produce both asexually and sexually, but we didn’t really make the connection between the latter method – also known as ‘horizontal gene transfer’ – and the passing on of antibiotic-resistant genes until very recently,” Cheeptham explains.

Most typically, bacteria produce offspring asexually by dividing their cells, creating an exact copy of the genome (known as vertical gene transfer). In this way, antibiotics are able to kill harmful bacteria as they’re dealing with an exact genetic replica of the harmful organism each time. However, during sexual reproduction, genes are exchanged between parent cells, and the offspring retains both sets of genes, creating a more complex organism. This can happen both within a species, and between species. Not all forms of E. coli, for example, are harmful. But there’s nothing to stop virulent strains of E. coli bacteria (such as O157:H7, or O104:H4) mixing with salmonella to create something altogether more lethal, and more difficult to kill.

To further complicate matters, most of the antibiotics we currently employ are considered "broad spectrum" drugs. Essentially, they’re engineered to kill all bacteria they come into contact with, whether good, bad or neutral. They are not specialised to deal with specific infections, let alone their mutated cousins. By wiping out our beneficial bacteria, these broad-spectrum antibiotics lower our immune system. And when our defences are down, new strains of antibiotic-resistant, and potentially fatal, superbugs can take hold. In short, when it comes to modern antibiotics, the standard medical procedure is to employ napalm when we really require a sniper.

Cheeptham is part of a growing coterie of scientists who believes an intelligent – if complex – solution exists. As of 2016, biologists at Indiana University estimated that 99.9999 per cent of all microbial species – some one trillion different species, whose natural chemical secretions form the base of all antibiotics – are still to be discovered. And Cheeptham believes that Canada’s Iron Curtain Cave – so called because of its bountiful iron deposits – represents one of our best chances at locating these new bacteria and using them to develop new antibiotics.

To Cheeptham, the search for the perfect cave has been a long journey. Born in Nakhon Sawan, Thailand, in 1970, to primary-school teachers, she credits her father for her interest in biology. “He graduated with a B.Sc. in Biology when I was 11,” she explains. “He took me to collect samples, and I became obsessed.”
Later, in 1992, after completing her own undergraduate degree in microbiology and biochemistry at Chang Mai University in northern Thailand, she began working alongside Fusao Tomita, previously head of research and development at Kyowa Hakko – at that time the third-largest pharmaceutical company in Japan. Under Tomita’s tutelage, Cheeptham’s focused her master's and PhD research on the possibility of developing new antifungal agents from fungi.

After finishing her PhD, she returned to Thailand in 1999 to continue her work at Chang Mai University. An article on cave bacteria by Diana Northup, an expert in geomicrobiology and biology at the University of New Mexico, convinced Cheeptham to make the switch to extremophiles. “I thought that if I went into a more extreme environment I would have a better chance of finding something new,” she explains.

Cheeptham‘s search for extremophiles initially took her to Thailand’s southern mangrove swamps, but she had a hunch that she would have better luck searching caves. The only issue was that the majority of accessible Thai caves have been opened up to tourists and outfitted with cement floors, artificial lamps and Buddha statues – not to mention scores of people trekking in and out each week. In other words, the antithesis of the pristine environments in which rare and unique bacteria are wont to develop. Along with her husband, Joe Dobson, Cheeptham made the move to his native British Columbia in 2001 and set up at Thompson Rivers the following year.

Ten years later, she discovered what she hopes to be the perfect cave. In their 2016 paper outlining their initial findings, (published in the journal Diversity) Cheeptham and her colleagues reported cataloguing 100 bacteria isolates in the Iron Curtain Cave. Of these, 12.3 per cent were unknown, and may even be completely new bacteria. So far, two of them have proved to be efficient against multi-drug-resistant microbial strains.

It’s early spring and I’m in the passenger seat of a truck as Rob Wall drives us through the remote backroads of the Chilliwack Basin, en route to the cave. Endless wooded hills stretch by on either side, and it is easy to imagine the grand network of underground systems hidden beneath the depths of the forest.

There, in the midst of a forest teeming with life, is a metre-wide metal door on the side of a mossy mound, like some kind of steampunk Hobbit hole. Wall and Storozynski are the only people able to provide access. Once the gate is open you will descend ten metres (down a pair of ladders laid end to end) into the bowels of the earth. There you’ll find half a kilometre of winding limestone tunnels, subterranean pools and claustrophobic crevices, stalagmites hanging from the ceilings, lords of the darkness.

As a member of the CRVC, Wall – now in his forties – acts as custodian of the Iron Curtain Cave, working with the government to control access. Its exact location is kept secret after other caves in the area were vandalised by weekend partygoers – an ongoing problem, to Wall’s immense chagrin. Protecting this unique resource is key a pair of metal gates protect the cave from the world above, and rigorous sterilisation procedures must be followed to prevent caving gear and scientific instruments from tainting the isolated bacteria.

Decontaminated or completely new caving equipment is required if the wearer has acessed another cave the same day. This is in order to prevent cross-contamination of organic matter, which may in turn destabilise a cave’s particular habitat, potentially destroying its unique – and possibly useful – bacteria population. Often, disposable Tyvek Coveralls are worn, then sealed in a plastic bag and sprayed with disinfectant upon exiting the cave. Easy-clean boots with rubber soles are preferred, and footwear must be changed before entering, and upon exiting, any cave. Naturally, scientific materials used in the collection of samples must either be sterilised, or previously unused and kept sealed in their packaging until required.

Storozynski takes point as he leads us into the depths. It is his job to ensure the safety of both Cheeptham and her team – and the cave environment – on their sample-collecting trips into the cave. While not as technically challenging as other caves in the vicinity, the Iron Curtain Cave has its share of tight squeezes, and requires an experienced guide to navigate safely.

Storozynski and Wall aren’t the only cavers putting their lives at risk in the hunt for new bacteria a number of cavers from the British Columbia Speleological Federation (BCSF) – the umbrella organisation for caving groups in the province – have ventured into underground vaults across the province to collect samples for Cheeptham. One cave is in grizzly-bear country so requires cavers to helicopter in to avoid attack. Another is only assessible if cavers scuba-dive in, then swim upwards into the cave – a technical feat beyond the abilities of most microbiologists. Without the vital work of these unpaid chaperones, Cheeptham’s research would stop dead in its tracks while the problem of antibiotic resistance continued to grow unimpeded.

During our time below ground, Storozynski leads us beneath low features and through tight crawl spaces, and is careful that we do not disturb the pristine cave walls by brushing against them. He is also tasked with maintaining the strips of luminous tape that guide us through the cave. Stray too far from the path and not only do you risk damaging the cave, you put yourself at serious risk, too towards the back of the cave a large, metre-wide hole on the edge of the taped-out path leads down into seemingly bottomless blackness. “It goes on forever,” Storozynski says, perhaps only half-joking.

Lake Baikal 'holds key to new advances in antibiotics'

Scientists make crucial new discoveries of bacteria, up to 30 million years old.

'One of the ways to find something new is to look somewhere where no one has ever looked before.' Picture: Galina Dvoeglazova

A global and highly competitive search is underway for new bacteria strains leading to fresh sources of antibiotics, with 'great potential' for SIberia to lead the way, according to leading scientists.

Maxim Timofeyev, director of the R&D Biology Institute at Irkutsk State University, said: 'One of the ways to find something new is to look somewhere where no one has ever looked before.

'We have found two locations which we're studying now. These are ancient caves and Baikal which have not been studied in this regard. Nature is still providing us with a massive area to study.'

Dr Denis V. Axenov-Gribanov, a leading specialist at R&D Biology Institute, heads the study of new microorganisms. Picture: ISU, Denis Axenov-Gribanov

'The search for new microorganisms producing new biologically active substances with antibiotic properties has particularly great potential in Siberia and at Baikal. On the one hand, our lands are far away from global research institutions, and on the other, we have multiple unique locations - unstudied and isolated caves and Lake Baikal with its ancient ecosystem.'

Dr Denis V. Axenov-Gribanov, a leading specialist at the same institute, said: 'One of the features of Siberian caves is that they are rather cold, only 2 to 4C.

'Among the caves of the Baikal region the most attractive for researchers are ancient and ramified caves such as Botovskaya, Okhotnichya and those of the Tazheranskaya steppe.

Among the caves of the Baikal region the most attractive for researchers are ancient and ramified caves such as Botovskaya, Okhotnichya, those of the Tazheranskaya steppe and Bolshaya Oreshnaya complex in Krasnoyarsk region. Pictures: The Siberian Times, Komanda-K, Denis Axenov-Gribanov

'Each and every cave is unique: Botovskaya cave is the longest cave in Russia, while the caves of the Tazheranskaya steppe date from when the ancient Lake Baikal was only forming, that is over 30 million years ago.' The lake is the oldest - and deepest - in the world.

'We have collected Baikal's endemic crayfish, caddis, and did a microbiological analysis. Two weeks afterwards, it wasn't yet clear whether there were bacteria. However, later we obtained 30 great strains, about 90% of which were active.'

Another success came at the world largest karstic cave in the Bolshaya Oreshnaya complex in Krasnoyarsk region, examined by Russian and German scientists.

In Bolshaya Oreshnaya complex in Krasnoyarsk region were obtained previously unknown biologically active compounds including antibiotics which inhibit growth of bacteria and fungi. Pictures: Alexander Balalin, Denis Axenov-Gribanov

'We obtained moonmilk substance and found 10 new strains of actinobacterias, producers of several antibiotics, from it,' he said. 'According to the study, they produce previously unknown biologically active compounds including antibiotics which inhibit growth of bacteria and fungi. For example, an active strain produces over 120 compounds, 100 out of which are new and haven't been studied before.'

He said: 'It is necessary to conduct numerous studies. to turn a compound in a commercial product. It will be essential to go through certain bureaucratic procedures, obtain substantial funding and prove your antibiotic is better, non-toxic and effective, and that you're moving in the right direction.'

Antibiotic Resistant Bacteria - Acceleration of their evolution (Apr/27/2006 )

Do you think that we are over paranoid about microorganisms in our environment and are creating a much more resistant population of bacteria? I heard on NPR today an epidemiologist talk about how you need to sanatize your computer keyboard at work and at home to prevent the spread of bacteria. Yeah I do agree with that . but do you think we are all taking this antibacterial craze a little too far. The other thing that amazed me was how he referred to everything as being contaminated with microorganisms. For the average listener I believe the word contaminated would sound a little scary. I sometimes worry that us scientists make people overly paranoid about the presence of bacteria. Not that I'm advocating never washing your hands .

triclosan is the source of all that is evil

paranoia also leads to overuse of antibiotics which leads to more resistant strains which leads to nastier illness once your normal flora are knocked down

kids eating dirt is like more vaccinations. and what's up with some of these antibacterial products these days? I've seen children's toys, toothbrushes, tupperware, lotion.

What about the supposed viral resistant/antibiotic tissue paper that I think it was Kleenex was putting out/advertising a while back ago??

All antibiotic soaps/ tissue paper and the likes should be banned!

When I first started in the lab, I was curious of what kind of bacteria lived on my skin. I touched several types of antibiotic plates and grew quite a few different species of bacteria (and fungi but that doesn't count).

I don't like the implication of my little experiment.

I´m from Germany and I think you´re right. Here, you can get Antibiotics only from a Doctor and only when you´re really ill. A cold for example does not count. We even have a saying: A cold lasts one week if you take medicine and 7 days when you do nothing. I´ve heard that in the USA you can buy antibiotics freely in a Drug store and every time you sneeze you throw in a few pills, just to be sure. The antibiotic concentration has to be enormous in your sewerage. Hysteric? Oh yes you are First I was glad to live here, when I heard about it, but then I was reminded that bacteria travel by Plane very easily.

In future, we may have many different types of aggressive antibiotic resistant bacteria.

I agree that as a society (here in Oz, at least), we are becoming way too paranoid- with antibacterial products of all kinds available on the market. It drives me nuts, and my poor non-science friends and family have to put up with my constant ranting about how bad this is!! Ahhhhh, I think I really get on their nerves.

I went to a really interesting talk by a paediatrics professor the other day (sorry her name escapes me just now), about how early exposure to microbes shapes our immune systems, and the implications of this in allergies and hypersensitivity etc etc.
Very interesting stuff.

we shouldnt forget that antibiotics and antibiotic-resistance are not inventions of mankind.

Most antibiotics are taken from moulds or certain bacteria or are improved derivates of these products. There is a chemical war going on for millions of years between the kingdom fungi and the bacterial domain. Mankind has only borrowed some of their weapons and modified them a little bit. In fact we were sort of helpless against most bacteria before we exploited the penicillium mould.

Bacteria developed antibiotic-resistence plasmids long before we appeared on earth. So why were the bacteria on Flemings famous agar plate not resistent? The reason is natural selection.

If you take a billion bacteria living somewhere on the s key of your kexboard for example there are probably 2 or 3 among them who are resistant to (for example) penicillin. They have this extra plasmid. Normally they would never get in contact with penicillin so in this population this extra plasmid is actually a disadvantage cause it costs the resistant bacteria some extra ATP to keep and express it (thats why only a minority has it in the first place).

Now if you spray antibiotics on your keyboard things change. The resistant ones will have an advantage and will multiply faster (or die less). So after some spraying you have increased the resistant bacteria in this population. Now when you press the s key and dont wash your hands, eat with your fingers and still wear a tshirt in the rainy september. well you know the deal.

But the thing is once you throw this old keyboard away or keep using this spray the bacteria on it will steadily lose their resistance again because it is again a disadvantage for them. So the idea of immune bacteria all around the globe is ridiculous. Come on! All the mould in this world had several million years time to accomplish this and failed. So how should we?

(Of course thats just an example. If you are an expert micro biologist you probably find a lot of factual errors here. Its ok.)

Are there any 70% ethanol-resistance bacteria or fungi?

I had similar paranoia and asked my Mircobiology professor a question when he was teaching antibiotic resistance. I never got the answer from him - either he didn't know or he was offended, I dunno. But, I had asked out of curiosity.

I had asked that if we are brushing teeth every morning from childhood, won't the bacteria in mouth be resistant to the toothpaste? After one fren learning dentistry told me how toothpaste works, I felt that I had asked wrong question

Three Domains of Life

Prior to 1969 organisms were classified into two kingdoms: the Plant Kingdom and the Animal Kingdom and on the basis of a cell, organisms were classified into two categories Prokaryotae or Monera (which comprised bacteria) and Eukaryotae (which comprised animals, plants, fungi, and protists). The concept of three domains of life was proposed by Carl Woese and others in 1969. The evolutionary model proposed by them is based on the difference in the sequence of nucleotides in ribosomal RNAs (rRNA) in cells and lipid structure of cell membrane and its sensitivity to antibiotics. According to them, all organisms can be classified into three different domains – Archaebacteria, Eubacteria, and Eukarya. All living things share certain genes, yet no two types of organisms have the same full sets of genes.

Scientists think that all living things have descended with modification from a single common ancestor. Thus, all of life connected. Yet, there are many different lineages representing different species. This diversity stems from the fact that genetic changes accumulate over the years. Also, organisms change as they become suited to their own special environments.

Archaea and Bacteria share a few common characteristic traits but do not have common ancestors. At the same time, they show some peculiar traits of their own. Carl Woese divided Prokaryotae into two groups – Archaea and Bacteria, and thus the concept of three domains of life came into existence.

Reasons for Selecting rRNA for Categorization:

  • It is present in all organisms and is the most conserved structure throughout nature
  • It is functionally similar between organisms and is involved in protein synthesis
  • Its sequence changes slowly and hence can be observed across long periods of time
  • The rRNA sequences can be aligned, or matched up, between 2 organisms.
  • The nucleotide sequence of rRNA gives a good indication of the relationship in different living groups.

Domain Archaea or Archaebacteria (Greek – archae – ancient):

  • These are the most primitive form of life.
  • These are the most ancient bacteria. Some fossils found with these bacteria are 3.5 billion years old. As they were from the time of harshest conditions on the earth, they adapted themselves to live in any harshest condition. These bacteria are special since they live in some of the harshest habitats such as extreme salty areas (halophiles), hot springs (thermoacidophiles) and marshy areas (methanogens).
  • They have unique cell membrane chemistry. Archaebacteria have cell membranes made of ether-linked phospholipids, while in case of bacteria and eukaryotes both make their cell membranes out of ester-linked phospholipids. The presence of this ether containing linkages in Archaea adds to their ability to withstand extreme temperature and highly acidic conditions.
  • Their cell membrane has no peptidoglycans. Archaebacteria use sugar that is similar to, but not the same as, the peptidoglycan sugar used in bacterial cell membranes.
  • They are not influenced by antibiotics that destroy bacteria.
  • Their rRNA is unique and is much different from the rRNA of bacteria. Their t-RNA and rRNA possess unique nucleotide sequences found nowhere else.
  • Most of the archaebacteria are autotrophs. They use pigment bacteriorhodopsin for photosynthesis.

Examples: Extreme halophiles – i.e. organisms which thrive in the highly salty environment, and hyperthermophiles – i.e. the organisms which thrive in the extremely hot environment, are best examples of Archaea.

Classification of Archaebacteria on the Basis of Habitat and metabolic activities:

Methanogens or Methanogenic Archaebacteria:

As they are anaerobic autotrophs, they produce methane as a result of their metabolic activities. They produce methane gas from carbon dioxide and acetic acid from sewage in the marshy condition.

Methanogens are present in the gut of several ruminant animals such as cows and buffaloes and they are responsible for the production of methane (biogas) from the dung of these animals. Methane is greenhouse gas that leads to global warming. Methanogens die in the presence of oxygen. Hence they can be found in swamp and marshes in which all oxygen is consumed. The typical smell in these areas is due to the production of methane. Methanogens help in the fermentation of cellulose. They do not decompose the organic matter but utilize the end products of decomposition.

Examples: Methanobacillus, Thiobacillus etc.

Thermoacidophiles or Thermoacidophilic Archaebacteria:

They are aerobic or facultative anaerobic chemoautotrophs. They are adapted to live in extremely hot (about 80 °C) and extremely low temperature (below freezing point) and acidic conditions (pH up to 2). They are found in hot springs (Sulfolobus), in refuse piles of coal mines (Thermoplasma) or geothermal area of Iceland (Thermoproteus).

Most of the thermoacidophiles use hydrogen sulphide as their energy source. They are chemotrophs

2S + 2H2O + 3O2 → 2H2SO4 + Energy (aerobic condition)

Under anaerobic condition, sulphur is reduced to hydrogen sulphide. They precipitate bicarbonate into carbonate due to their activities.

Examples: Thermoplasma, Picrophilus, Thermococci, Pyrococcus, Sulfolobus, etc.

Halophiles or Halophilic Archaebacteria:

They are aerobic or facultative anaerobic heterotrophs. They live in salty environments such as a Great Salt Lake or the Dead Sea, marshes, brine, salt-rich soil where the salt concentration is in range of 2.5 M to 5 M. They have high intracellular concentrations. Their enzymes and ribosomes function efficiently at higher salt concentration.

They contain special photoreceptor pigment called bacteriorhodopsin. Due to which they acquire a purple colour. Bacteriorhodopsin protects halophiles from strong solar radiations. It helps in the synthesis of ATP. It shows the chemotrophic nature of nutrition.

Examples: Halobacteria, halococcus, etc.

Domain Bacteria or Eubacteria:

  • These are prokaryotes.
  • The cell walls of bacteria unlike the domains of Archaea and Eukarya, contain peptidoglycan.
  • Their membranes are made of unbranched fatty acid chains attached to glycerol by ester linkages.
  • They are sensitive to antibiotics.
  • They are autotrophs synthesize their own food, or heterotrophs. Most of the bacterial species are heterotrophs. They get their food from organic matter.
  • Naked DNA molecule lies in the cell cytoplasm.
  • Only one set of genes, usually in a single-stranded loop is present.
  • There is a great deal of diversity in this domain, such that it is next to impossible to determine how many species of bacteria exist on the planet.
  • Cyanobacteria and mycoplasmas are the best examples of bacteria.

Domain Eukarya:

  • Cells have a eukaryotic organization.
  • The cell membrane is composed of a tri-laminar protein-lipid-protein layer similar to that in bacteria.
  • Peptidoglycans are not found.
  • They are resistant to traditional antibiotics.
  • Cells are organized into tissues in case of kingdom Plantae as well as kingdom Animalia.
  • The cell was is present only in the kingdom Plantae.
  • Eukaryotes are further grouped into Kingdom Protista (euglenoids, algae, protozoans), Kingdom Fungi (yeast, mold, etc.), Kingdom Mycota (Phycomycetes, zygomycetes, ascomycetes, basidiomycetes, Deuteromycetes) Kingdom Plantae (bryophytes, pteridophytes, gymnosperms, and angiosperms) and Kingdom Animalia (all animals).

Another system of grouping organisms divides all life into six major categories called kingdoms. The six kingdoms consist of four kingdoms within the domain Eukarya (the Kingdoms Animalia, Plantae, Fungi, and Protista), one kingdom in the domain Archaea (Kingdom Archaea) and one kingdom in the domain Bacteria (KingdomBacteria). Many biologists recognize these six kingdoms and three domains, but some biologists use other systems of grouping.


  1. Groot

    the Relevant point of view, attractive

  2. Nikozragore

    Will you be able to quickly find such a single sentence?

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