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The Use of Antibiotics in AgricultureFinal Draft

Microbiology

Ryan Kirdahy

April 28, 2017

The Use of Antibiotics in Agriculture

Agriculture is the science that encompasses the raising of plants, fungi, and animals for

the purpose of food and other products. These products could be related to fuel, manufactured

goods like clothing, medicinal products, and food. All areas of agriculture are exposed to many

different harmful environmental factors such as bacteria that could harm the plants or animals.

One of the most influential advances in modern medicine is the discovery of antibiotics. Within

the past 50 years there has been a rapid development in new antibiotics that are meant to help the

agriculture industry combat against these diseases and infections. Antibiotic use in agriculture

has many advantages that humans have profited from economically as well as through food

production and overall wellness. However, with the advantages comes many disadvantages that

are more recently becoming prevalent. Human health and antibiotic resistance are up for much

debate recently. This has led to different laws and regulations from different organizations to

help monitor the usage of antibiotics. There is a large economic influence related to antibiotic

use in these fields that people tend to prioritize (Tortora et al. 2015). There are risks and

consequences that must be addressed in order to prevent doing more harm than good. If society

fails to do so, there is a significant risk that more problems will arise from the overuse of

antibiotics, especially in agriculture.

Antibiotics are used in humans and in agriculture to aid in eliminating bacterial diseases

that could be harmful These antibiotics work through several different mechanisms in order to
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perform their tasks. Antibiotics can either be bactericidal or bacteriostatic. Bactericidal drugs

induce cell death and eliminate the cell that is targeted. Bacteriostatic drugs do not induce cell

death or destroy the cell, but simply inhibit further growth of cells. Bactericidal antibiotics cause

the inhibition of four important synthetic processes. These four processes include the inhibition

of cell wall synthesis, the inhibition of protein synthesis, the inhibition of RNA synthesis, or the

inhibition of DNA synthesis (Kohanski et al. 2010). Antibiotics affect different types of bacterial

cells differently. They have more of an impact on gram-positive cells than they do on gram-

negative cells.

Bacteria can be distinguished into two separate classification groups. These

classifications are based off of the structure as well as the function of the bacteria. The two

classification groups of bacteria are gram-positive bacteria and gram-negative bacteria. Gram-

positive bacteria have the distinguishing figure of multiple layers of peptidoglycan which form a

thicker membrane. Gram-positive cells also have teichoic acids present. Teichoic acids are

comprised of a phosphate and an alcohol. Teichoic acids have a negative charge so they are

responsible for the movement of positive ions (cations) entering and exiting the cell.

Additionally, teichoic acid plays a part in the growth of cells. This helps them avoid a large

amount of cell wall destruction and also prevents the potential lysis of the cell (Tortora et al.

2015).

In comparison, gram-negative cells are somewhat different than gram-positive cells. One

of the most obvious differences is that gram-negative cells have a very thin layer of

peptidoglycan. During a gram stain this would cause the cells to stain pink. Unlike gram-positive

cell walls, gram-negative cell walls lack teichoic acids. In gram-negative cells, there is an area

called the periplasm. This area holds transport proteins and degradative enzymes.
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The thin layer of peptidoglycan puts gram-negative cells at risk for mechanical breakage. Gram-

negative cells have an outer membrane that consists of lipopolysaccharides, phospholipids, and

lipoproteins. The outer membrane plays a crucial role in the functions of a gram-negative cell.

This type of bacteria can even avoid phagocytosis due to the strong negative charge. Gram-

negative cells also use the outer membrane to protect themselves from antibiotics, detergents,

bile salts, heavy metals, and digestive enzymes. They also use porins which are proteins in the

membrane that form channels to allow some permeability. Only certain molecules can pass

through the membrane. For instance, iron, vitamin B12, nucleotides, peptides, and disaccharides

are all molecules that have the potential for being able to enter a gram-negative cell (Tortora et

al. 2015). Gram-negative cells are progressively gaining resistance against antibiotics. (Kuliper

and Dissel 2010). This type of bacteria is also common in human disease and can be obtained in

various ways. Gram-negative bacteria can be cause foodborne and waterborne diseases. They can

be transmitted sexually or even through vectors like insects or other animals (National Institute

of Health 2016).

Not only can bacteria be transmitted easily, they can also adapt so that they are more

dangerous and virulent. One of the ways this occurs is through nnjjnfjkn gene transfer.

Horizontal gene transfer is one of the possible factors that could be behind antibiotic resistant

organisms forming. This process works by transferring genetic information among two

organisms that are in the same generation (Tortora et al. 2015). Horizontal gene transfer works in

three ways. These three ways are transformation, conjugation, and transduction. Transformation

involves DNA being taken up by bacteria from the surrounding environment. Conjugation is the

transfer of genetic information between cells by direct contact. Finally, bacterial viruses, also

known as bacteriophages, relocate the genes to a different cell in transduction. This evolution
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will continue, and as it progresses the bacteria can gain more and more of a resistance to the

drugs that originally eliminated them (Ventola 2015). Another way genetic information can be

passed along is through vertical gene transfer. This type of genetic transfer is passed down from

an organism to its offspring. Spontaneous mutations can occur which can improve or decrease a

bacterias resistant capabilities (Todar 2008). It only requires one cell to develop a resistance to

antibiotics to begin these processes. Preventing bacteria from becoming antibiotic resistant is

crucial for the health of society as well as the disadvantages this would cause for the agriculture

industry.

Antibiotic use can prevent millions of dollars from being lost to disease in agriculture.

Every single year as much as fifty to one-hundred million dollars are lost due to bacterial

diseases in fruits and vegetables. This is a devastating number for the growers who rely on high

yields to make profits. This kind of economic loss is a highly motivating factor for famers to use

antibiotics. The more resources they can produce, the better. It is better for them because more

product means they are able to make more profit, and it supplies a larger quantity of food to the

general population. These diseases may not only cause disease in localized cases, but can spread

quickly and ruin an entire area (McManus 2017). In the short term, it benefits many organisms as

well as humans because of the increased amount of resources produced, but the long term

impacts are up for debate.

Farmers do not want to lose valuable crops to something combat fire blight during times

where the disease is predicted to have sizeable infection periods (Gusberti et al. 2015).

Not every antibiotic will work under every condition. Streptomycin is the safest and most

effective antibiotic for that situation. The antibiotics that are used on crops must fall under

certain criteria. The antibiotic must be able to work on the plant or even in the plant. The
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antibiotics must be able to survive the conditions they may be exposed to such as endure UV

irradiation, oxidation varying temperatures as well as not be washed away by rainfall. It is

critical that the antibiotic used is safe for the organism as well as the humans consuming the

organism. The antibiotic must select for resistant pathogens at an extremely low rate. The last

example is extremely important because if it selected resistant pathogens at a high rate it would

increase the possibility of creating more antibiotic resistant bacteria (McManus 2017).

Streptomycin was the most universally used as the most effective and safest antibiotic.

Strains of bacteria have become resistant to streptomycin and that has reduced its ability to

effectively control disease. The use of streptomycin is effective on twelve different plant species.

Streptomycin can be poisonous to plants when at high concentrations which is why streptomycin

is sprayed on the surface of the plants in low concentrations (McManus 2017).

An additional example of an antimicrobial used for plants is oxytetracycline. The most

popular use for oxytetracyline is on several types of fruits like pears, nectarines, and peaches.

Oxytetracyline is not as popular and must be delivered by injection. Tetracycline injections

require more work and are more expensive, but are more beneficial under certain conditions. It

may be necessary when streptomycin resistant strains are present in the area. Also, it is more

practical to use on individual trees rather than larger numbers such as a forest or in large

agricultural settings (McManus 2017). Overall, antibiotic use on trees comprises an extremely

small portion of antibiotics usage when compared to human consumption and livestock. About

0.1% of all antibiotics produced are used on plants. Around 30,800 pounds of streptomycin as

well as 26,700 pounds of oxytetracylcine were produced and used on fruit trees in 1997

(McManus 2017).
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Even though plants comprise a small portion of antibiotic use, it is still something

important to look at when purchasing food, particularly food that is labeled as an organic

product. Sometimes, even crops labeled as organic can be impacted greatly impacted by

antibiotics. To be defined as organic, the farming method avoids using supplements such as

antibiotics, pesticides, growth hormones, and more. This means that organic organisms should

not have any exposure to antibiotics of any kind. Despite the efforts to avoid these products

contaminating a farmers crops, sometimes this can be unsuccessful. Animals could possibly act

as vectors in transporting antibiotics. Animals that are exposed to antibiotics tend to excrete up to

90% of the antibiotics in their feces and urine. Sometimes these products are used to make the

manure that is used to fertilize other crops. Also, antibiotics can end up in the ground water or

surface runoff. These crops can absorb the excreted antibiotics. The higher the amount

antibiotics present in the ground, the greater the levels that are absorbed by the plants (Ventola

2015).

When it comes to agriculture, the use of antibiotics in animals is far more prevalent than

the use of antibiotics in plants. Out of all of the antibiotics that are sold in the United States, it is

believed that about 80% are used in animals (Ventola 2015). Antibiotics help animals fight off

infections as well as stay healthy just like they do for humans. This can lead to animals having

extended lives and ensure that a greater portion of the population will not die from disease.

Animals live in overcrowded, densely populated areas which are prone to being generally

unsanitary environments (Brown et al. 2017). A study done by PLOS ONE on pigs in different

environments represented this concept. Pigs that lived in more stressful environments were more

likely to experience especially severe results from an infection in comparison to pigs living in

less stressful environments. In the study, eight of the fourteen pigs (57%) living in the stressful
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conditions developed A. pleuropneumonia lesions compared to only one out of fourteen pigs

(7.1%) living in less stressful environments experiencing lesions. These results are fairly

noteworthy and show the impact that conditions can have on these animals. Many times farmers

compensate for these results by excessively using antibiotics to treat or prevent the animals from

experiencing similar results. This is an effective method of keeping the animals healthy short

term, but leaves the opportunity for antibiotic resistant bacteria to develop (van Dixhoorn et al.

2016)

The previous study shows how improper environmental factors can influence disease in

increase the need for antibiotic use. However, animals will become ill, and there has to be a way

to ethically take care of them. Antibiotics can be used to treat mastitis in cows. Mastitis is

essentially the inflammation of udder tissue and mammary glands on cows due to a bacterial

infection. In order for treatment, the cows teat must be cleaned as well as swabbed with alcohol.

A tube with a short cannula is inserted approximately halfway into the steak canal and the

antibiotic is dispensed into the teat cistern (Hurley 2009).

While the prevoius treatment shows that antibiotics may help heal animals with disease, it

is estimated that about 90% of antibiotic use in the agricultural setting is for growth promotion

while only about 10% is used for infection treatment (Mehndiratta and Bhalla 2014). Antibiotics

are not only used to treat diseases, but they are used to prevent disease in the first place as well

as increase the growth of the animals. This type of use is what leads to the dangers of overuse of

that they can prevent. Antibiotics can be supplied to the crops to help them survive as well as

prevent disease outbreaks in the first place. Fire blight is a disease caused by Erwinia amylovora

and attacks pome fruit trees such as pears and apples. This disease has devastated populations of
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fruit trees across the United States and Europe. Streptomycin is an antibiotic that Switzerland

allows to be used to antibiotics.

A study done by Applied and Environmental Microbiology tested the incidence of

antibiotic resistance in Escherichia coli isolates from broiler chickens that had feed

supplementation such as antibiotics. The results of this study showed that there was not a

substantial difference in the broiler chickens weight after the experiment. However, every one of

the 197 Escherichia coli isolates that were examined showed multi-resistance to antibiotics such

as novobiocin, clindamycin, tylosin, erythromycin, penicillin, as well as additional antibiotics.

This goes to show that misuse of antibiotics can lead to hazardous results. There was not a

significant reason to give the chickens the antibiotics because there was not even a difference in

growth between the antibiotic group and control group (Diarra et al. 2007).

Of all the benefits and risks mentioned so far, the most serious is the potential for

antibiotic resistant bacteria to emerge. The risk of antibiotic resistant bacteria infecting

agriculture is dangerous, however there should be a much larger concern for the possibility of

these antibiotic resistant bacteria being able to infect humans (Phillips et al. 2004). Bacteria will

mutate and under optimal conditions they could mutate into strains that antibiotics can no longer

treat. The excessive contact that the different areas of agriculture are exposed to in terms of

antibiotics will lead to antibiotics resistant bacteria. Humans are in danger from antibiotic

resistant bacteria developing. Humans can be infected through consumption of a contaminated

source of food or water, direct contact with animals, or by other infected humans. Ingestion of

antibiotic resistant organisms can be the cause of obtaining disease. This mainly causes

gastrointestinal illnesses. Although these types of cases are not very common, they still pose a

risk to human health (Chang et al. 2014).

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Another concern is the transmission of antibiotic resistant strains infecting humans that

originated in livestock. If an antibiotic resistant strain was able to cross the species barrier, then

humans would be at an increased risk. As of right now there are still too many unknowns when it

comes to the transfer between species of antibiotic resistant bacteria. There are several isolated

cases of antibiotic resistant bacteria originating in livestock and infecting humans, but it is not

extremely common. There are also several cases of animals obtaining infections from human

strains of bacteria. Again, these cases are extremely uncommon, however they are occurring

(Chang et al. 2014).

With all of these risks, there is one thing that still goes unchanged and that is that humans

are tremendously dependent on agriculture and the various goods we obtain from it. The use of

antibiotics is highly overused and has become entirely irresponsible. There is a legitimate threat

of bacteria evolving into antibiotic resistant strains that could possibly infect humans. Antibiotics

have lifesaving benefits, but humans are using them to the point of making it dangerous to

rationalize the economic benefits and higher yield in product. There needs to be a balance found

in order to not put society at risk. The risks far outweigh any possible benefit that could arise

from the levels of antibiotics that are currently being used. If this is not taken seriously, the

incidences of bacteria developing antibiotic resistance will become more common. There will be

more bacteria like methicillin resistant Staphylococcus aureus.

A very common example of an antibiotic resistant bacteria is methicillin resistant

Staphylococcus aureus (MRSA). This pathogen evolved to be resistant to methicillin as well as

other antibiotics. Methicillin resistant Staphylococcus aureus is fairly common globally. It can be

extremely common in hospital settings. When present in hospital settings, methicillin resistant

Staphylococcus aureus poses as a threat to causing life threating illnesses. Originally methicillin
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resistant Staphylococcus aureus was thought as a health care associated pathogen, but now

methicillin resistant Staphylococcus aureus is believed to stem from community acquired

infections (Mehndiratta and Bhalla 2014).

There have been strains of methicillin resistant Staphylococcus aureus that have been

linked to livestock, specifically companion animals, swine, and people who are in constant close

contact with animals. Methicillin resistant Staphylococcus aureus associated with livestock has

been documented in several different countries. This opens the exceedingly dangerous possibility

to other bacteria moving from country to country due to modern transportation (Mehndiratta and

Bhalla 2014).

The desire for animal food products is increasing very rapidly due to the constantly

increasing population. Developing countries are experiencing an especially large demand (Hao et

al. 2014). Many developing countries have very little or even no regulations regarding antibiotic

use. These countries do not have the resources to supervise antibiotic resistance either. Low and

middle income countries are progressively producing and using more and more antibiotics for

their livestock. It is believed that between the years 2010 and 2030, as much as a third of the

increase in antibiotic use for food animals globally will come from developing. Many of the

developing countries struggle when it comes to managing antibiotic use regardless of the risk

that antibiotic resistant bacteria pose. It simply is not a priority when it comes to their countrys

affairs. The global effort to prevent antibiotic resistant bacteria from becoming an increasing

threat can be nullified because antibiotic resistant bacteria simply cannot be contained to one

area. Antibiotic resistant bacteria do not follow geographic boundaries and will spread across

nations. Even to nations that follow proper protocol and try to reduce the global risk for allowing

the rise of antibiotic resistant bacteria. Several low and middle income countries such as India,
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China, Thailand, and South Africa have begun to contribute to the cause of slowing antibiotic

resistance bacteria. However, there are still many low and middle income countries that need to

improve their efforts (Founou et al. 2016).

There are plenty of examples of improper use and regulations in livestock in developing

countries. One example in Zambia is the finding of extended spectrum beta-lactamase producing

bacteria (ESBL) in poultry (Chishimba et al. 2016). Extended spectrum beta-lactamase

producing bacteria are dangerous because they are able to effectively destroy antibiotics. They

are able to accomplish this because of the enzymes they secrete. Extended spectrum beta-

lactamase producing bacteria can exhibit cross-resistance which is the ability to avoid being

affected by antibiotics because of previous exposure to a substance that was similar. Extended

spectrum beta-lactamase producing bacteria can be difficult to detect and can widely range in the

diseases they cause (Rawat and Nair 2010). ESBL-producing Escherichia coli was the specific

bacteria strain being tested. It was observed that out of the 384 chickens sampled, 77 (20.1%)

had extended spectrum beta-lactamase producing E. coli. Further testing proved that 66 of the 77

(85.7%) showed that the isolated extended spectrum beta-lactamase producing E. coli was

resistant to beta-lactam as well as other antimicrobial agents. This is very concerning because

these were chickens that were meant for human consumption. This proves that there is a

desperate need for further antibiotic regulations and policy in Zambia as well as other developing

countries (Chishimba et al. 2016).

In comparison, many developed countries experience the luxury of having enough

resources to make a serious effort at controlling the excessive use of antibiotics. Many European

countries such as Norway and the Netherlands are experiencing decreases in antibiotic usage.

The European Union banned antibiotic use for growth-promotion in 2006. Fortunately,
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developed countries have the ability to investigate and research the effects more thoroughly as

well. Developed countries are doing what they can to try to prevent the irresponsible and

unnecessary use of antibiotics in agriculture by supporting each other as well as supporting the

low and middle income countries. They are doing this by encouraging the decrease in antibiotic

use as well as continued research into antibiotic resistant bacteria. This is a global problem and

must be a global effort to solve it (Founou et al. 2016).

The group in charge of monitoring the resistance of antibiotic bacteria in the United

States is the Center for Disease Control. Specifically, a division known as the National

Antimicrobial Resistance Monitoring System for Enteric Bacteria (Centers 2017). Another group

that is known to work with this danger is the Environmental Protection Agency (EPA). The

Environmental Protection Agency tries to help regulate the usage of antibiotics, especially when

it comes to crops. One of the main services that the Environmental Protection Agency focuses on

with crops is helping growers predict the optimal time to spray their crops with antibiotics. The

Environmental Protection agency will give recommended time periods where they believe that

spraying the antibiotics to prevent certain disease will be the most effective. This helps the

farmers economically by saving them from over spraying their antibiotics and using too much

throughout the season. It also decreases the amount of exposure crops have to antibiotics.

Overall, the Environmental Protection Agency hopes this will decrease the chance of antibiotic

resistant strains forming (Centers 2017).

Public awareness is key as well. Governments can try to help discourage the decrease in

antibiotic use, but the general population must be informed as well. The ignorance of not

knowing the risks that irrational use of antibiotics can pose some serious health risks for

everyone. Resources such as social media are key when it comes to supporting and raising
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awareness. There are many activist groups that are trying to inform the public and gain increased

support of decreasing the use of antibiotics in agriculture (Founou et al. 2016).

Unfortunately, diseases are still a factor and eliminating antibiotic use may lead to

farmers losing many of their livestock and crops to illness and disease. In addition to that, this

could potentially lead to a food shortage. An option to help alleviate this issue would be to use

vaccines to prevent diseases and infections in the animals. This option should help the livestock

stay healthy, but also reduce the extreme dependence that farmers have on antibiotics. It is

important to support these types of movements as well as improve overall farming practices. If

the living conditions of animals are improved by keeping the environment safe and clean as well

as having adequate living space, the animals will not be at as high of a risk when it comes to

diseases. Organic farming is one way that supports these beliefs and ideals. These organic farms

are much more sustainable and friendly towards the cause of reducing the quantity of antibiotics

used (Founou et al. 2016).

Antibiotics have an enormous role in agriculture that does have some positive impacts,

but is proving to be more risky than beneficial. The excessive use of antibiotic for nonessential

reasons in agriculture are leading to the emergence of antibiotic resistant bacteria. This poses a

serious risk that will be hard to contain if it gets out of hand. Society as a whole needs to be more

careful and knowledgeable about the way we use antibiotics in agriculture, because that is where

the majority of antibiotics are being used. This poses a serious threat, and once it gets out of

control, it will be too late. Bacteria will adapt and evolve until antibiotics become useless against

them, which will lead to severe health risks for humans down the road. Attached below is a

reflection of how my personal views about antibiotics in agriculture were impacted.

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When I first chose the topic Use Antibiotics in Agriculture I did not know a great deal

about the subject. I had a very basic understanding of it. I was fairly excited to learn a bit more

about this specific topic in order to get some facts straight, and clear up any misconceptions that

I had. My honest reaction was that I was incredibly shocked at how little I actually knew about

this topic.

I did not fully understand in what proportion we are using antibiotics in our agricultural

systems. The more I read the more I was taken aback by the statistics. Another topic that

concerned me was that large portion of the antibiotic usage that had nothing to do with actual

illness or infection of the animals or livestock. These antibiotics were used as a prevention

method. What was even worse than that, there was a good deal of the percent of antibiotics that

were used for growth promotion.

Instead of making an ethical decision to improve living environments or reduce the stress

that the livestock have to endure, the agriculture industry favors the excessive use of antibiotic

distribution. There needs to be a serious adjustment to agricultural sustainability and animal care

in order to improve that situation.

I think that it is important to realize where we have gone wrong in order to improve the

current situation to prevent it from getting any worse. I supported the idea of many countries,

especially developed countries leading the way in research and regulations. I recognize why this

could be difficult for many developing countries or low and middle income countries. Some of

these countries are without the funding or capabilities to perform research or implement

regulations. They are just trying to improve their agricultural techniques in order to produce

higher quantities of food.

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I learned a great deal about how antibiotics work to eliminate and kill bacteria. I did not

realize that there were different techniques to either kill the pathogen, or just prevent the growth

of it. I was also surprised to learn that there were four different possible synthesis inhibiting

processes involved with antibiotics.

Going along with that, also learned a significant amount about how bacteria are

constantly evolving to become more resistant to the antibiotics we use to kill them. Both of these

process make much more sense now. It makes it easier to understand when the two can be

compared.

Something that I am always told to look out for while grocery shopping is to try to buy

organic. I was raised to believe that this was a better option because of the chemicals that are

used to feed the animals or protect the plants. From what I have learned I am much more

encouraged to support farms that use organic agricultural techniques. Something that surprised

me from this section was how that even organically raised organisms could be contaminated by

antibiotics.

Something that definitely startled me and was an overall wakeup call was methicillin

resistant Staphylococcus aureus (MRSA). This antibiotic resistant bacterium is very prevalent

globally already. I remember hearing about methicillin resistant Staphylococcus aureus in high

school as an athlete, and that a school near us had an outbreak of it in their locker room. These

bacteria are extremely hard to treat because antibiotics do not work on them. When I learned that

there are strains of methicillin resistant Staphylococcus aureus that originated in livestock and is

showing up in humans and vice versa I was very shocked. If the trend of antibiotic overuse

continues I am concerned about the repercussions that may be involved. Who knows what type
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of strains could mutate into a human pathogen. This could be a very real issue if the world as a

whole cannot try to prevent this from continuing on the path that we are on.
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