novel approach

Scientists are hunting for genes that enable bacteria to become resistant to life-saving antibiotics

Disease-causing bacteria are becoming resistant to antibiotics more quickly than we’re discovering new ones.

From the muddy bottoms of deep ocean trenches to Komodo dragon blood, scientists have scoured Earth’s remote corners in search of molecules that could yield the world’s next antibiotic. They hope to discover powerful new medicines against which bacteria have not yet evolved defenses. It’s a high-stakes pursuit. Disease-causing bacteria are becoming resistant to antibiotics more quickly than we’re discovering new ones.

That’s a big problem for humans. Infections that throughout the 20th century became easy to treat because of antibiotics have today become deadly. In the United States alone, more than 2 million people each year are infected with bacteria that can’t be killed by the drugs that were meant to stop them. At least 23,000 of those people will die as a result of their infections.

“[I]n the antibiotic ‘arms race’ against bacteria, humanity is rarely ahead,” wrote a team of researchers headed by microbiologist Gautam Dantas in a recent review article. Dantas, an associate professor at Washington University in St. Louis, is trying to change that.

We can no longer outrun antibiotic resistance by simply mining nature for new compounds, Dantas explains. He and others now are tackling the problem head on – by hunting for the genes that enable bacteria to become resistant to life-saving medications. Finding and decoding these genes may provide fresh clues about how antibiotic resistance emerges – and how to shut it down.

Unearthing the antibiotic resistome

Antibiotics are chemical substances that kill or slow the growth of bacteria. They are often thought of in terms of their medicinal properties that stop infections in humans, but many bacteria in the environment naturally produce chemicals with antibiotic properties, too.

In fact, some of our most important antibiotic discoveries have come from microorganisms in the environment. Scientists isolated penicillin, the world’s first antibiotic, from a type of mold in 1928. Other antibiotic discoveries – including streptomycin, the first medical cure for tuberculosis – came from soil bacteria. In the span of a generation, people stopped dying from injuries and illnesses such as pneumonia, scarlet fever and syphilis.

(Graphic: U.S. Centers for Disease Control and Prevention)
(Graphic: U.S. Centers for Disease Control and Prevention)

Scientists aren’t exactly sure why bacteria started making antibiotics in the first place, but they’ve been at it for a long time – probably since around the time bacteria emerged about 3.5 billion years ago. And since they were essentially creating their own poison with the antibiotics, the bacteria needed an antidote. So, over time, they evolved a suite of antibiotic resistance mechanisms.

Researchers have found genes encoding antibiotic resistance just about everywhere they’ve looked in the environment – on fossils scraped from the walls of subterranean caves or buried beneath feet of permafrost, even in the healthy gut microbes of people in a Yanomami Amerindian village who have never had contact with modern medicine.

“It’s an ancient feature of virtually every microbial ecosystem on the planet,” says Dantas. Scientists call this collection of resistance-conferring genes the antibiotic resistome.

Dantas and other researchers have spent the past decade cataloguing the resistomes of various environments – soil, farm animals, wastewater treatment plants, even the human gut. A stark picture is beginning to emerge – they’ve found genes encoding resistance to our most important antibiotic medicines lurking nearly everywhere they looked.

Growing problem

If antibiotic resistance is ancient, why is it just becoming a problem for humans now?

“We’ve applied a very big stress to the natural system over the last couple of decades,” says Andrew Edwards, a microbiologist at Imperial College London.

Antibiotics are some of the most commonly prescribed medications on the planet. While there’s no doubt antibiotics can be life-saving, they’re also commonly misprescribed for minor ailments and illnesses that don’t respond to antibiotics, explains Edwards. In the United States alone, an estimated one in three antibiotic prescriptions isn’t necessary, according to the US Centers for Disease Control and Prevention.

Then there’s the use of antibiotics in farm animals. Some poultry and other livestock receive antibiotics in their feed. Low doses of antibiotics help them grow bigger on less food, cutting the cost of production. A US Food and Drug Administration report last year found that sales of medically important antibiotics for use in farm animals in the United States rose 26 percent between 2009 and 2015.

Chicken being fed tetracycline as treatment for the intestinal infection colibacillosis. (Photo: Lucyin/Wikimedia Commons)
Chicken being fed tetracycline as treatment for the intestinal infection colibacillosis. (Photo: Lucyin/Wikimedia Commons)

Bacteria are really good at improvising their way out of trouble – it’s how they’ve survived on the planet for 3 billion years, explains Gerry Wright, a microbiologist at McMaster University in Ontario, Canada. “Each time we use an antibiotic, it creates the opportunity for that adapt-or-die dichotomy,” he says. Because bacteria are so bountiful, and they reproduce so quickly, it doesn’t take long for some to develop mutations that confer resistance and then, in the presence of the antibiotics, to dominate populations.

All of this use has resulted in an increase of antibiotic resistance genes in non-disease causing bacteria found in the environment. A 2010 study from the Netherlands reported that genes conferring resistance to some tetracyclines, a class of antibiotics, were 15 times greater in soil bacteria by 2008 than the 1970s.

Doctors discovered resistance to penicillin soon after the drug was introduced, but antibiotic resistance wasn’t initially appreciated as a problem, because new antibiotics were being discovered at a quick pace throughout the 1950s and 1960s (what some call the golden age of antibiotics). However, the problem soon became obvious as the rate of discovery of new antibiotics began to slow through the second half of the twentieth century, Edwards explains.

ID’ing environmental reservoirs

Finding resistance genes to medically important drugs in bacteria from a manure pit or a ball field isn’t the same as finding them in disease-causing bacteria in the hospital. Each day we’re bathed in a sea of microbes, and most don’t make us sick.

But bacteria can swap DNA. Some bacteria send packets of DNA into their environment. Others pick up and incorporate those packets into their own genetic material. It’s called horizontal gene transfer, and it’s what many bacteria do instead of sex to spread their genes.

A benign soil-dwelling microbe could theoretically lend its antibiotic resistance genes to a human pathogen in this way. Researchers have long suspected that disease-causing microorganisms could dip into environmental pools of antibiotic resistance, but experts weren’t sure whether this was actually happening at any meaningful rate.

In 2012, Dantas and colleagues showed for the first time that it was. They found soil microbes that shared a set of antibiotic resistance genes with human pathogens. Exchange of resistance genes between soil and clinic established soil as a key player in the network of pathogenic resistance, explains Dantas, though their research did not show the direction of the transfer – whether the genes moved from soil to pathogen or pathogen to soil.

Morten Sommer, a professor of bio-sustainability at the Technical University of Denmark, now is trying to understand which environmental reservoirs pose the most risk to human medicine.

“We want to know how and where that transfer to human pathogens is most likely to occur so we might be able to prevent the spread of resistance genes out of those environments,” says Sommer. He doesn’t have the answers yet, but he’s probing the antibiotic resistomes of soil, farm animals, wastewater treatment facilities and even the “good” bacteria of the human gut.

Finding a solution

Armed with a greater knowledge of the antibiotic resistome, scientists can devise new ways to counteract resistance to the drugs we already have and the antibiotics of the future.

Historically, humans have taken a reactive approach to antibiotic resistance — waiting to act until some superbug shows up in the clinic. Dantas and others now are taking a proactive approach. In May, Dantas along with several other Washington University researchers discovered a group of compounds produced by bacteria that could block resistance to tetracyclines by “gunking up” the cellular machinery some bacteria use to make the drugs ineffective. They’re now exploring whether these resistance-blocking compounds could be given together with existing antibiotics to help preserve their efficacy.

It’s just one example. Other researchers are using the resistome to come up with new combinations of antibiotics that could help slow the spread of multi-drug resistance, where bacteria are resistant to more than one antibiotic. In the antibiotic discovery pipeline, some new compounds make better candidates than others, but researchers often can’t weed out the duds until resistance shows up in the testing phase — a time-consuming and costly process. Understanding the likelihood of a rare genetic swap from one environment to another may help scientists save time and resources by predicting earlier which new compounds may be more or less susceptible to widespread resistance.

Dantas is hopeful about the possibilities, though none of it really matters if we don’t curtail our current antibiotic use, he points out. Antibiotic resistance is a fact of nature. It’s not going away unless bacteria go away (in which case we’d be gone too). There are steps we can take to stay ahead of it or even slow it, but “we have to protect the armamentarium if we want that shot,” he says.

This article was first published on Ensia.

We welcome your comments at
Sponsored Content BY 

How sustainable farming practices can secure India's food for the future

India is home to 15% of the world’s undernourished population.

Food security is a pressing problem in India and in the world. According to the Food and Agriculture Organization of the UN (FAO), it is estimated that over 190 million people go hungry every day in the country.

Evidence for India’s food challenge can be found in the fact that the yield per hectare of rice, one of India’s principal crops, is 2177 kgs per hectare, lagging behind countries such as China and Brazil that have yield rates of 4263 kgs/hectare and 3265 kgs/hectare respectively. The cereal yield per hectare in the country is also 2,981 kgs per hectare, lagging far behind countries such as China, Japan and the US.

The slow growth of agricultural production in India can be attributed to an inefficient rural transport system, lack of awareness about the treatment of crops, limited access to modern farming technology and the shrinking agricultural land due to urbanization. Add to that, an irregular monsoon and the fact that 63% of agricultural land is dependent on rainfall further increase the difficulties we face.

Despite these odds, there is huge potential for India to increase its agricultural productivity to meet the food requirements of its growing population.

The good news is that experience in India and other countries shows that the adoption of sustainable farming practices can increase both productivity and reduce ecological harm.

Sustainable agriculture techniques enable higher resource efficiency – they help produce greater agricultural output while using lesser land, water and energy, ensuring profitability for the farmer. These essentially include methods that, among other things, protect and enhance the crops and the soil, improve water absorption and use efficient seed treatments. While Indian farmers have traditionally followed these principles, new technology now makes them more effective.

For example, for soil enhancement, certified biodegradable mulch films are now available. A mulch film is a layer of protective material applied to soil to conserve moisture and fertility. Most mulch films used in agriculture today are made of polyethylene (PE), which has the unwanted overhead of disposal. It is a labour intensive and time-consuming process to remove the PE mulch film after usage. If not done, it affects soil quality and hence, crop yield. An independently certified biodegradable mulch film, on the other hand, is directly absorbed by the microorganisms in the soil. It conserves the soil properties, eliminates soil contamination, and saves the labor cost that comes with PE mulch films.

The other perpetual challenge for India’s farms is the availability of water. Many food crops like rice and sugarcane have a high-water requirement. In a country like India, where majority of the agricultural land is rain-fed, low rainfall years can wreak havoc for crops and cause a slew of other problems - a surge in crop prices and a reduction in access to essential food items. Again, Indian farmers have long experience in water conservation that can now be enhanced through technology.

Seeds can now be treated with enhancements that help them improve their root systems. This leads to more efficient water absorption.

In addition to soil and water management, the third big factor, better seed treatment, can also significantly improve crop health and boost productivity. These solutions include application of fungicides and insecticides that protect the seed from unwanted fungi and parasites that can damage crops or hinder growth, and increase productivity.

While sustainable agriculture through soil, water and seed management can increase crop yields, an efficient warehousing and distribution system is also necessary to ensure that the output reaches the consumers. According to a study by CIPHET, Indian government’s harvest-research body, up to 67 million tons of food get wasted every year — a quantity equivalent to that consumed by the entire state of Bihar in a year. Perishables, such as fruits and vegetables, end up rotting in store houses or during transportation due to pests, erratic weather and the lack of modern storage facilities. In fact, simply bringing down food wastage and increasing the efficiency in distribution alone can significantly help improve food security. Innovations such as special tarpaulins, that keep perishables cool during transit, and more efficient insulation solutions can reduce rotting and reduce energy usage in cold storage.

Thus, all three aspects — production, storage, and distribution — need to be optimized if India is to feed its ever-growing population.

One company working to drive increased sustainability down the entire agriculture value chain is BASF. For example, the company offers cutting edge seed treatments that protect crops from disease and provide plant health benefits such as enhanced vitality and better tolerance for stress and cold. In addition, BASF has developed a biodegradable mulch film from its ecovio® bioplastic that is certified compostable – meaning farmers can reap the benefits of better soil without risk of contamination or increased labor costs. These and more of the company’s innovations are helping farmers in India achieve higher and more sustainable yields.

Of course, products are only one part of the solution. The company also recognizes the importance of training farmers in sustainable farming practices and in the safe use of its products. To this end, BASF engaged in a widespread farmer outreach program called Samruddhi from 2007 to 2014. Their ‘Suraksha Hamesha’ (safety always) program reached over 23,000 farmers and 4,000 spray men across India in 2016 alone. In addition to training, the company also offers a ‘Sanrakshan® Kit’ to farmers that includes personal protection tools and equipment. All these efforts serve to spread awareness about the sustainable and responsible use of crop protection products – ensuring that farmers stay safe while producing good quality food.

Interested in learning more about BASF’s work in sustainable agriculture? See here.

This article was produced by the Scroll marketing team on behalf of BASF and not by the Scroll editorial team.