Alien Invaders Beyond the Microscope:

The Antibiotic Apocalypse Explained

Danyal Chaudry
Period: 3
Advisor: Dr. Kiehl
Abstract

For decades since penicillin was first discovered by Alexander Fleming in 1928,
antibiotics have been used as a golden bullet for use against harmful bacteria. They have been
used to clean and disinfect wounds, keep livestock healthy, and have saved millions of
uncounted lives since their inception. But as the theory of evolution states, over time organisms
will inherit physical and behavioral traits that will allow them to adapt to their environment and
produce more offspring. This has been apparent with how bacteria have developed different
genotypic and phenotypic traits that have allowed them to resist such antibiotics that have been
used for decades. This has stemmed from the use of antibiotics as a commodity that is prescribed
without the batting of an eye, overdose, the use of antibiotics in the agricultural industry, etc. If
this problem is not addressed, many medical professionals and esteemed experts in the field have
stated that it will bring us back to the medical dark ages. It has the potential to kill millions in the
future, and is projected to kill more people than cancer by 2050. The use of new genetic
modifying techniques as well as new polymers and proteins have given hope, but more research
needs to be done to be able to conclusively find a way to solve the problem that will save
millions of lives in the future.
Introduction

Antibiotics have been used as a magic bullet for decades since their inception by

Alexander Fleming in 1928. Before they were discovered, it is estimated that millions died of

bacterial infections each year such as Gangrene, pneumonia, tuberculosis, etc. The bullets that

were used in the Civil War, for example, were created with a design that prevented skin from

being able to be healed back, causing deadly infections. But when they were discovered they

were used the golden bullet that would be able to cure all bacterial infections, as experts of the

time thought. As the public began to buy into it, the demand rose, and pharmaceutical companies

turned away from selling things such as bacteriophages like Eli Lilly did. Use of antibiotics

soared, and pharmaceutical companies kept producing more and newer ones. As the use of

antibiotics soared, the uses grew from hospital use to daily use and use in the agricultural

industry. The increased use of these antibiotics quelled bacteria for some time, but as the theory

of evolution and natural selection states, organisms will develop certain traits that will allow

them to survive and create more offspring, until eventually the population of that species has

completely adapted to their environment. This has happened in bacteria, and is evident in the

way that bacteria have developed certain genotypic and phenotypic traits that allow them to

survive antibiotics. The research into new methods of antibacterial products has given hope

through the discovery of new gene technologies as well as new proteins and polymers, but a

sustainable and legitimate solution still needs to be found. This paper will provide context of

bacterial resistance and how it stemmed, examine possible solutions for this problem, and

determine the viabilities of such solutions.

Review of Literature

Bacterial resistance to antibiotics has proven to be a major problem in the world today,

and is projected to become even greater and much worse than it is right now. This has stemmed

from a multitude of things. One aspect of the origin of this problem is the way that we use such

drugs to meet the needs that we have created for ourselves and using them as nothing more than

a commodity. According to a study conducted by the CDC in early May of 2016, it came to a

shocking conclusion that one in three antibacterial prescriptions in doctors offices in the United

States are unnecessary. Antibiotics are lifesaving drugs, and if we continue down the road of

inappropriate use well lose the most powerful too l we have to fight life-threatening infections,

says CDC Director Tom Frieden, M.D., M.P.H.

An example of an unnecessary prescription would be when a patient has a viral infection.

Most of the time that antibiotics are wrongly prescribed, the doctor has is only partially sure that

it is truly a bacterial infection. In some cases, the infection could simply be viral, to which

antibiotics are of no use. But if the patient comes in with an infection, and it is deemed to be

viral, sometimes the doctor feels obliged to prescribe something for the patient to be able to take

home with them and use. If the doctor does not prescribe anything to the patient and the patient

goes home and gets even more ill, then the doctor feels that they will receive complaints and will

have to fear for their jobs. The CDC plans to implement better diagnoses methods and open up

communication between doctor and patient, but this is only the human side of the problem.

The other side of the problem is the use of antibiotics in the agricultural industry. The use

of antibiotics in the agricultural industry has soared since agricultural companies have realized

the powerful effects of antibiotics on increasing profits. By using antibiotics, agribusiness is able
to keep animals in unsanitary and cramped conditions, reducing living space and thus costs of the

animals and are able to keep them alive by using copious amounts of antibiotics. The agricultural

industry is also able to fatten up their animals by giving them antibiotics with their feed,

increasing the weight and amount of meat that they are able to sell, again increasing profits. (D.

Nelson, personal communication, Jan. 5, 2017).

The use of antibiotics in the agricultural industry has far overshadowed the use of

antibiotics in the medical field for humans. According to an article by CNN in 2015, In 2012,

80% of all antimicrobial agents sold were used in animals, and 60% are the same antibiotics that

are used in humans. (Christensen, J.). In the same article it also reports a statement issued by the

American Academy of Pediatrics, stating that the current antibacterial crisis was being caused by

a misuse and overuse of antibiotics, and they called on the agricultural industry to use less

antibiotics in their feeds given to animals. The discovery of certain resistant bacterial strains

have also caused concern in that they have been discovered primarily in pig farms. This

problem has only been exacerbated by the administering of antibiotics to livestock, providing

bacteria more opportunities to develop resistance to these antibiotics. (Healy, M.). The

agricultural industry is a slow moving ship though, and some large companies in the industry are

openly against the abandonment of antibiotics in the practices of raising their livestock. As

reported in 2016, the COO of the third largest poultry producer in the United States, Sanderson

Farms released a statement saying, "There is not any credible science that leads us to believe

we're causing antibiotic resistance in humans. (Strom, S.)

The two major problems in this wider crisis are the false prescriptions and the abuse by

the agricultural industry. But there is another problem that is subtler than the other two, but just
as important. It is the awareness of the American public of to the problem of antibiotic

resistance. According to a survey in the Oxford Journals in 2016 of the American publics

knowledge of the problem and analysis of it, 70% of respondents in the survey disagreed of

responded neutrally that antibiotic resistance was a major problem in American hospitals.Most

respondents were not very well versed in antibiotic resistance, and 89% of respondents said that

people could develop an immunity to antibiotics. (Carter, R. R., Sun, J., & Jump, R. L.P. ).

Without the publics knowledge of antibiotic resistance, the pressure that is necessary from the

public to be able to force the market to move toward antibiotic free meat, as well as pushing the

government to develop new initiatives and policies in doctors offices that will ensure better

diagnostics will not be there. If the push from the public is not there, large corporations will

continue to make profits on the expense of the health of the public, and research as well as new

initiatives and policies cannot be spearheaded to ensure the health and prosperity in the future.

Now that context has been given about where the problem stems from, it is now essential

to delve into how bacteria develop resistance. There are two categories that bacteria develop

resistance, genotypic traits and phenotypic traits. When a bacteria has traits that that are

genotypically defined to resist antibiotics, that means that it has the genes necessary to resist

antibiotics. When a bacteria has traits that can be phenotypically defined, that means that the

bacteria has physical traits that allow it to resist antibiotics. There are two genotypic traits,

according to the WHO, these are antibiotic degrading enzymes and antibiotic altering enzymes.

Antibiotic degrading enzymes inactivate the antibiotic by destroying them chemically when they

enter the bacteria. Antibiotic altering enzymes attach to the antibiotic when they enter the

bacteria, not allowing them to bond to anything, therefore negating the effectiveness of the
antibiotic. The two phenotypically defined traits are efflux pumps and cell wall resistance. Efflux

pumps a transport protein, which is an extremely efficient way to get harmful things inside of

the bacteria out efflux pumps pump harmful substrates out of the bacteria. (Webber, M. A., &

Piddock, L. J.V.). This pump can be very useful to the bacteria in environments that are saturated

with antibiotics, and they can develop MDR (multiple drug resistance). Finally, cell wall

resistance is the phenotypically defined trait of the bacteria that develops a stronger cell wall

with more selective transport proteins and defenses that keep the antibiotic from even entering

the bacteria, allowing the bacteria to resist antibiotics.

Research Methods and Data Collection

To conduct research, the student obtained research from multiple different sources and

articles and examined them to determine their effectiveness in relation to his research question.

For the research, the student set out with the research question How will antibiotic resistance

affect us going forward and what solutions are possible to fight it? The researcher hypothesized

that antibiotic resistance will prove to be a major problem for the human race going forward, and

different methods in gene manipulation and new proteins and polymers would provide the

solution to antibiotic resistance. The articles used by the researcher in the meta-analysis were of

new methods and solutions to combat antibiotic resistance, and had solutions that were viable.

For example, in the first article examined (Ying Wing et al., 2015), the relation of resistance was

discussed with the nutrition levels present in the environment and a single-cell level. The

researchers in this study placed a resistant strain of bacteria in differing nutritional environments

with the same amount of antibiotic in each. The results showed that the bacteria in the
environment that had lower nutrition levels were the least able to express resistance, and had the

least survival rate in relation to the bacteria that were in a higher nutrition environment.

The second article (Elena Blzquez et al., 2017) examined by the researcher examined

the effect of UV-C irradiation on the SDP given to pigs in feed. SDP, or spray dried plasma, is a

protein source given to pigs that has copious amounts of antibiotic in it to be able to counteract

the bacteria in it. In this article, the scientists placed samples of SDP in a UV-C irradiation

system to see of the system could clean the SDP of bacteria. The study concluded that the

irradiation of the pig feed was an effective alternative to using antibiotic in the feed to counteract

the bacteria in it, and antibiotic can be avoided from being used.

The third article examined by the researcher (Teik Hwa Ong et al., 2017), the scientists

examined the effect of chitosan-propolis on the elimination of resistant strains of bacteria.

Chitosan-propolis is an extract from bees that has been proven to be toxic to bacteria. In this

experiment, the researchers put the chitosan-propolis in a container with the resistant bacteria,

and left another container with just the bacteria as a control. The container that had the

chitosan-propolis in it eliminated all of the bacteria and the researchers concluded that

chitosan-propolis was very effective in eliminating resistant strains of bacteria.

The fourth article examined by the researcher (Daniel C. Nelson et al., 2016) was of

bacteriophage usage. The scientists in this study used a bacteriophage known as PlyC, and

administered it to resistant strains of streptococci to examine the effectiveness of PlyC in

eliminating resistant strains of streptococci. The PlyC was shown to lyse the resistant

streptococci upon impact, and was very efficient in eliminating the resistant streptococci. As Dr.
Nelson, a researcher who worked on the study said, it is like steel girders in a building, if you

take out too many, the building collapses.

Results and Data Analysis

The data acquired in the meta-analysis relates to the research question and hypothesis in

the manner of solutions to the problem. In all of the articles, the solutions were experimented on

and their effectiveness was shown to be able to resist antibiotics. The different solutions were

examined for their viabilities as well, and their potential uses were assessed. They all had

different strengths and weaknesses, and in some cases the combinations of different solutions

compensated for the other solutions weaknesses. For example, the nutrition levels of an

environment can be manipulated to allow chitosan-propolis nanoparticles to be able to

effectively eliminate the bacteria in an area. An another example would be that bacteriophages

could be used to lyse any remaining bacteria that were not irradiated by UV-C radiation. The

collection and comprehensive study of all of these articles provides a set of viable solutions to be

able to be used in the fight against bacterial resistance. (See Appendix A).

Upon completion of the meta-analysis, the researcher concluded that the best possible

solution would be to use the different solutions as a mix that compensated to each others

abilities and weaknesses, and not to limit oneself to simply one solution. The chitosan-propolis

could be used when the diagnostics are not clear, the UV-C irradiation of SDP can take care of

one aspect of the agricultural side, and the nutrition level manipulation can be used as a last

minute attempt to quell resistant bacteria. This answered the research question and hypothesis by
providing a set of viable solutions to the problem of antibiotic resistance looking ahead into the

future.

Discussion and Conclusion

The findings that have been produced in this research apply to the greater audience by

providing them with knowledge of different solutions to the problem of antibiotic resistance.

Many millions of people can benefit from this research as it applies to every human alive today.

It ranges from the knowledge of when to use antibiotics and what meats and products to

purchase, to the larger research that is taking place that will change the future of the medical

world as seen today.

The findings in this research have the implications of affecting research on antibiotic

resistance. The solutions and different studies compiled illustrates that no single solution can any

longer provide a comprehensive solution as antibiotics have for decades, as bacteria will develop

resistance to the new solution as well. But the different solutions can be used to each others

advantage to be able to compensate for each other and not allow for bacteria to be able to

develop a resistance due to the different treatments being used.

The limitations of this research is that only four different and new solutions were

researched, and the solutions researched need to be refined upon more to be able to be legitimate.

For example, more accurate diagnostics are in order for bacteriophages to truly be legitimate, and

chitosan-propolis needs to have a more efficient way to produce a solution, etc. More refinement

upon the solution in this research need to be made, and more solutions need to be incorporated as

well, as the four solutions discussed in this paper cannot possibly save the world on their own.
 In the future, a comprehensive solution to antibiotic resistance can be developed based on

the research discussed in this article. From prevention methods such as different agricultural and

medical practices, as well as new methods such as the ones discussed in this paper, a

comprehensive solution can be reached that will have the potential to save millions of lives.
Appendix A:

Article #1 Article #2 Article #3 Article #4

Purpose of the To examine how To examine the To examine the To examine the
study different effect of UV-C effect of effectiveness of
nutrition levels irradiation on chitosan-propoli PlyC in
can affect the the inactivation s nanoparticle eliminating
resistance of of certain formulation in resistant strains
beta-lactamase antibiotic antibacterial of streptococci.
bacteria at the resistant bacteria ability against
single-cell level. for SDP in pig resistant bacteria
diets. and biofilms.

Methods A microfluidic Propolis was PlyC was placed

device was used Enterococcus bought and in differing
to create faecium, prepared in quantities with
different cells Salmonella ethanol or ethyl resistant strains
for E. coli choleraesuis, acetate. The of Streptococci,
bacteria to go and Salmonella bacterial biofilm and the
into with typhimurium was prepared, as effectiveness of
different bacterial strains well as the the
nutrition levels, were placed in a resistant bacteriophage
but the same UV-C reactor bacteria. The was evaluated.
amount and type system. These propolis was
of antibiotic in strains were then administered to
each. tested with the the biofilm and
UV light to see the resistant
if it could bacteria.
irradiate the
bacteria.

Results The cells with The reduction Chitosan-propoli PlyC had a

less nutrition rates of the s inhibited positive effect in
culture resisted bacteria bacterial growth efficiently
the antibiotics subjected to the and biofilm destroying the
less and had a UV light was formation. It resistant strains
 higher death rate robust, and also altered the of streptococci.
as well as lower showed that this genes expressing
growth rate than UV irradiation resistance by
the cells that had killed bacteria. forming
more nutrition biofilms,
concentrations. increasing
susceptibility to
treatment.

Effect on Limiting the UV light can be Using a solution PlyC and other
research nutrition that used to irradiate of bacteriophages
bacterial cells SDP and can chitosan-propoli are useful in
can receive in reduce the s, resistant eliminating
our bodies can amount of bacteria can be resistant
change their antibiotics used killed or altered bacterial strains.
susceptibility in agriculture for to change
from antibiotics. pig feed. expression of
resistance.

Projected Nutrition-blocki A large system A solution of Bacteriophage

solutions ng solutions can that can irradiate chitosan-propoli that can be
be introduced to SDP at a scale to s that is safe injected to kill
the bloodstream match the diets enough to be resistant
of an infected of pigs and the administered to bacterial strains.
patient that only output of large sick patients.
block it from farms.
bacteria.

Viability It will be very The viability of Creating a Creating a

difficult to a UV system to solution will be bacteriophage
create a solution process this very viable, but solution that can
to be able to aspect of pig making it so that be injected is
accomplish this feed is it will only very viable.
and do it extremely viable inhibit bacterial
selectively to and attainable. growth in the
bacterial cells. bloodstream
may prove to be
difficult.

Conclusions/Li Bacterial UV light has Chitosan-propoli Bacteriophages

mitations antibiotic been shown to s has the require very
resistance can be irradiate some potential to be accurate
dependent on species of used as a diagnostic
nutrition levels antibiotic therapeutic agent methods to be
in the resistant bacteria to combat effective.
environment, for pig feed, bacterial
especially in resulting in less biofilms and
heterogeneous antibiotics in their formation,
nutrition agribusiness. but more
environments. specialized
methods of
administration
must be made.
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