Growing Resistance: How Plant Agriculture Contributes to AMR

Growing Resistance: How Plant Agriculture Contributes to AMR

If you tell Anuradha Chowdhary, Ph.D., to eat an apple a day, she’s likely to tell you about pathogenic, drug-resistant strains of the fungus Candida auris that might be lingering on the surface. "An apple is great," she might say, "but be sure you wash it first."

Apples might not seem like the most obvious reservoir for pathogenic microbes that don’t respond to most of today’s potent antimicrobials. But at the same time, according to Chowdhary, a mycologist at the V.P. Chest Institute in Delhi, India, it’s not surprising. "We’re looking at sources in the environment because everything is connected," she explained. "Fruit is 1 example."

Research points to practices in plant agriculture and crop production that may help pathogenic, resistant microbes reach people. According to Chowdhary, who studies the molecular ecology of pathogenic fungi, it’s a global problem for which some countries may have fewer resources, and it's an avenue of transmission that’s often overlooked. But we neglect it at our peril: research focusing exclusively on human health and transmission in places like hospitals and other health care settings only captures a cross-section of the larger, interconnected system by which antimicrobial resistance (AMR) moves through the world.

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Practices in plant agriculture and crop production may assist pathogenic, resistant microbes in reaching humans and animals.
Source: iStock.

Fruits, Fungus and Farms

Between March 2020 and September 2021, Chowdhary worked with microbiologist Jianping Xu, Ph.D., at the McMaster University in Hamilton, Ontario, to look for C. auris in ordinary places. The research group visited markets and orchards in Delhi and across northern India. In total, they collected 84 fruits, all grown on trees. Those included 62 apples, 20 of which had been picked from orchards, and 42 of which had been purchased from a market. Some of the orchards used organic farming methods; others didn’t. The researchers tested samples from the surfaces of the fruits and found fungal species on all of them. These findings were reported in mBio in March 2022.

On 8 of the 62 apples—representing 13% of the sample—they found pathogenic, drug-resistant strains of C. auris. This fungus can cause severe infections and, because it colonizes the skin, spreads easily, especially in health care settings. If those strains manage to infect people, they can be dangerous. In an analysis of 192 hospitalizations in the U.S. related to C. auris, researchers from the U.S. Centers for Disease Control and Prevention (CDC) found a mortality rate of 34%.

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Researchers found that 13% of their apple samples contained pathogenic, drug-resistant strains of C. auris.
Source: iStock.


"When we think about AMR, most of us think about the consequences in terms of health, in particular for humans and animals," said Jorge Pinto Ferreira, D.V.M., Ph.D., food safety officer at the Food and Agriculture Organization of the United Nations in Rome. "And for the good and the bad, the global dimension of a health issue is often evaluated by the number of human deaths it causes." But that is not the whole picture.

The intersection of AMR and plant production affects the food chain and human health around the planet, and experts argue that the best solutions to addressing the spread of AMR will require a wide view. "The focus must be on the global nature of the problem," Ferreira said. "It is more than well-known and recognized today how interconnected everything is."

From Soil to Salad: Opportunities for Resistance

Plants begin with a seed in the soil, and to really understand how agricultural processes for growing plants can contribute to the spread of AMR, researchers are studying resistant genes and microbes that aren’t pathogenic to humans. "Antibiotic resistant bacteria associated with plants in the greatest numbers are not human pathogens, but rather commensal bacteria often associated with food spoilage," said Karl Matthews, Ph.D., a food microbiologist at Rutgers University in New Brunswick, N.J.

By studying how these microbes spread, researchers can better see how AMR moves through the food cycle. "Recognizing that non-pathogenic bacteria associated with food crops can be antibiotic-resistant is essential," he said. His research has 2 main arms: developing plant-derived antimicrobials and understanding how the use of antibiotics in crop production facilitates the spread of AMR.

Resistant bacteria, pathogenic or not, have plenty of places to live, including in and around the soil. They also have many ways to get to the soil if they aren’t there in the first place—e.g., the seeds themselves and the workers who plant them, as well as organic soil additives, water that is used in agriculture and manure that is used as fertilizer.

For example, antibiotics are regularly added to livestock feed to prevent or treat bacterial infections, and waste from those animals can be used as fertilizer. A review by an international collaboration of researchers connected the use of fertilizers, including cattle manure, chicken manure, swine manure and sewage sludge, to the presence of antibiotics—tetracyclines and fluoroquinolones—and corresponding antibiotic resistance genes in the soil.

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Resistant bacteria have many ways to get to the soil if they aren’t already there: manure used as fertilizer, organic soil additives, the water used in agriculture, the seeds themselves and the workers who plant and harvest the crops.
Source: iStock.


Microbes (and those corresponding resistance genes) that are introduced to the soil via such agricultural practices can then hitch a ride on the plants in the surrounding environment. A study published in July 2021 connected the dots: researchers from the University of Nebraska-Lincoln found that the use of animal manure directly contributed resistant microbes and resistance genes to the soil. In fact, altered soil composition accounted for more than 60% of the AMR genes found on the outside of leaves of lettuce that grew in the sampled soil.

In addition, plants might be treated with antibiotics themselves. Similar to the way antimicrobials have led to major gains in health care by turning previously fatal infections into treatable, survivable ones, they’ve also led to healthier, more productive crops. For example, tetracyclines, a family of antibiotics used to treat bacterial infections in humans, are also injected into tree trunks to prevent diseases like huanglongbing (HLB) disease. They are also applied to pears and apples to prevent fire blight.

After harvest, the food might be treated with antibacterials or antifungals for packaging and shipping, which both reduces the bacterial population and offers an opportunity for resistance to persist. Azoles are potent drugs used to treat human infections by Aspergillus fungi; they’re also the most-used antifungals in agriculture, applied to fruit to prevent the growth of mold during shipping and storage. Some researchers worry that the use of azoles in agriculture may be making matters worse by killing off susceptible fungi and leaving resistant strains to flourish. Importantly, the CDC has reported that those infected with azole-resistant strains of Aspergillus are up to 33% more likely to die from the infection than those infected with non-resistant strains.

Furthermore, according to Ferreira, plasmids, which are tiny loops of DNA that can carry antibiotic-resistant genes, have been identified in both plant and human pathogens. As a result, harmless microbes that live on the plants may develop resistance, and then pass that resistance on—likely through horizontal gene transfer—to neighboring, pathogenic microorganisms that could transfer resistance to humans and animals. Fruits and vegetables eaten raw and unwashed offer a potential opportunity for resistant microbes and genes to enter the human gut, and some studies hint at the possibility of gene transfer to the existing gut bacteria.

Researchers hope the growing understanding of how resistance travels through the plant food cycle will inform tomorrow’s strategies for lowering risk.

The increasing menace of antimicrobial resistance has led researchers around the world to track how AMR factors into the food cycle, crop production and farming practices. "It is an issue that goes clearly beyond health," Ferreira said. "Food safety, food security, food production, one way or another, all rely in higher or lower degrees on the use of antimicrobials."

At the local, national and even international levels, food safety experts have begun to think deeply about stewardship, sketching out a set of recommendations about best practices and methods for reducing the spread of AMR, and the risks associated with it. "Ultimately, it has to be a global effort," Ferreira said. "Microbes do not recognize boundaries."

Looking to One Health for Best Practices

Experts point to the management of antibiotics in agriculture as an opportunity to use transdisciplinary approaches—including those in the One Health concept—to stem the spread of resistance.

By trying other methods before turning to antibiotics, farmers could promote the growth of healthy crops without disrupting the ecosystem. For example, integrated pest management uses knowledge about threats to crops and involves strategies like rotating crops or identifying those weeds and pests that require control. It also includes recommendations for how to keep antimicrobials to a minimum, and how to minimize contamination and risk to people and animals. Recent studies also suggest bacteriophages may be useful in eliminating harmful, resistant bacteria.

Of course, antimicrobial stewardship won’t be easy. The use and misuse of antibiotics in medicine and livestock is well-documented, but in horticulture and plant agriculture the impact and spread of resistance are less well-studied. Plus, regulations vary by region and country. Brazil does not allow antibiotics to be used in pesticides; neither does the European Union. Other countries limit their use to certain crops, while still others have no legislation at all. "These countries [without legislation] could be disproportionately affected by AMR because the use of antimicrobials is not monitored, and regulations are either minimal or not enforced," Ferreira said.

Matthews, at Rutgers, concurred that closer monitoring of the agriculture production environment could help stem the problem. "Measures at the field or processing levels will contribute to reducing antimicrobial-resistant bacteria to crops, but some of these measures may not be implementable in countries with limited resources," he said. Matthews also noted that education could help. Greater awareness that unwashed, uncooked fruits and vegetables could harbor pathogenic, resistant microbes "must be achieved," he emphasized.

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Experts emphasize the importance of a One Health approach, which brings together considerations of humans, animals and the environment.
Source: iStock.


Experts agree that what will likely be most beneficial is a global, transdisciplinary, One Health approach, which brings together considerations of humans, animals and the environment at the local, national and even international levels.

"We need to be realistic, and to be aware that there is no 1 simple solution that will magically make the AMR issue disappear in a fast way," said Ferreira. Still, recent findings that elucidate the movement of microbes through plant agriculture suggest a way forward—supporting science-based practices that can be translated at the local level (e.g., informing farmers of the dangers of the overuse of antimicrobials). But everyone involved in farming—from farmers to governments—will need to support international efforts to curb the risk to human and animal health.

"Global strategies for stewardship focus on the development of integrated, sustainable agrifood systems," Ferreira said. "And on the implementation of the idea that antimicrobials are global common goods that we are all responsible for."

Read the USDA's Reflection on a Decade of AMR Response


Author: Stephen Ornes

Stephen Ornes
Stephen Ornes is a science and medical writer who lives in Nashville, Tenn. He's also the creator and host of "Calculated," a podcast collection of stories about people at the intersection of math, art and culture. Visit him online at stephenornes.com.

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