Super Bug
Super Bug
Super Bug
Yeah, so I guess I was the frst U.S. patient with the New Delhi Super Bug. Instead of my normal stay in the hospital,
I was there for weeks. I barely got to see anyone since I was quarantined. According to the doctors, I probably picked
up the bacteria when I was getting dialysis at the hospital on my vacation in India. I really don’t understand why my
infection was a super bug. What exactly is a “super bug”? What makes infection with a super bug diferent from my
other infections?
While I sat there in the hospital room, I couldn’t watch any more daytime television, so I decided to do a couple of
internet searches. I mean really; I’m not a pre-med student for nothing. So, Wikipedia frst…it seems that a super bug
is just a hyped up way of saying that the drugs used to treat the infection don’t. Tese “super bugs” apparently have
antibiotic resistance. Here’s one of the “visuals” I found:
So while I thought this information on antibiotic resistance was helpful, what exactly does this have to do with me
sitting here forever? I Googled “Super Bug” and found a variety of news stories. Here's an “extract” from one of them:
“Doctors in India aren’t surprised that the Super Bug probably originated there. Drug
control there is poor and common antibiotics have become inefective in India. Some
reasons may be because people can buy powerful antibiotics over the counter, leading
to overuse. Tey also take small doses and discontinue treatment in order to save
money. Tere are no current antibiotics, nor any in development, that can kill New
Delhi Super Bug on their own.” –Vinny Ciancio (AccessRx)
Questions
1. What do you think could allow some of the bacteria to live even in the presence of antibiotics? (Hint: Are all
the bacteria in a population the same? How might they difer?)
2. What are the biological, social, or cultural factors that may have infuenced the increased resistance of this
strain of bacteria to antibiotics? (i.e., what could have infuenced the development of New Delhi Super Bug and
infuenced its spread?)
Exercise
Te acquisition of antibiotic resistance in certain bacterial species in a given location occurs over time. How does
antibiotic resistance relate to evolution?
Form a group of 4 students. Defne each of the principles of evolution listed below. Ten compare them to Sam’s story
of the antibiotic resistant bacteria. Explain how bacterial antibiotic resistance demonstrates each principle. Designate 1
student in the group to report your fndings to the rest of the class.
• Phenotype vs. genotype
• Diversity
• Allele and allele frequency
• Gene pool
• Selection or natural selection
• Population bottleneck
• Heritable traits
• Adaptation
• Population vs. individual
• Mutation
• Lateral gene transfer
Your Task
Examine the graphs and fgures associated with
the two experiments below and then answer the
questions that follow.
Experiment 1
Scientists examined how much antibiotic it would
take to kill the bacterium E. coli, with and without
the NDM-1 gene. Te NDM-1 gene encodes an
enzyme that breaks down antibiotics rendering
them inactive. A graph of their results is presented
to the right.
Te x-axis represents the specifc antibiotic tested as
well as the class of antibiotic that it belongs to. Each
class of antibiotics has similar chemical structure
and mechanism of action. For example, penicillin
inhibits remodeling of the peptidoglycan cell wall
of bacteria, which weakens the cell wall, making
them susceptible to be lysed. In contrast, macrolides
inhibit bacterial protein synthesis by binding
irreversibly to the 50S subunit of the ribosome,
inhibiting translocation of peptidyl-tRNA.
Te y-axis represents the amount of antibiotics needed to kill the bacteria. It is represented as a percentage of the
amount needed to kill the E. coli that does not contain NDM-1 gene (wild type). Tus for all the antibiotics, wild
type is 100%. For example to kill the wild type bacteria it takes 1 g/mL Piperacillin; in contrast, to kill E. coli with
NDM-1 it takes over 256 g/mL Piperacillin. Terefore, the percentage of wild type to kill the E. coli with NDM-1 is
25,600%. Please note that the y-axis is represented on a log scale.
Experiment 2
Te mechanism of action of diferent antibiotics varies, but the quinolone class of antibiotics acts to prevent DNA
replication. For bacteria to replicate their DNA, they need to separate the strands of DNA from each other. Two key
enzymes help accomplish this task: DNA gyrase (gyrA) and topoisomerase IV (parC).
Over a 14-year period, 828 E. coli isolates were collected from patients with urinary tract infections (UTI) similar to
Sam’s. Ten these isolates were examined for quinolone-specifc resistance and the presence of mutations in the gyrA
and parC DNA sequences that gave E. coli quinolone resistance.
Te frst table below describes these results from the randomly chosen isolates. Te sequences of the gyrA and parC
genes were known, so the sequences of the isolates were compared to the known sequence. Te mutations found are
described in the chart by the amino acid encoded by unmutated DNA, the position of the amino acid, and the amino
acid that the DNA was mutated to. For example, gyrA has a Serine at position 83 with a DNA sequence corresponding
to a TCA codon. Te sequence of an isolate at the same position in the DNA was TTA. Tis is a codon for Leucine
instead of Serine. Ten the percentage of quinolone-resistant bacteria that contained this mutation is listed.
gyrA parC
Mutation Resistant Mutation Resistant
Isolates Isolates
Final Amino Containing Final Amino Containing
Start Amino Acid Position Start Amino Acid Position
Acid Mutation Acid Mutation
Arginine or
Serine 83 Leucine 100% Serine 80 93.6%
Isoluecine
Valine or
Glycine or (Glycine,
Aspartic Acid 87 98.7% Glutamic acid 84 56.4%
Asparagine Alanine,
Lysine)
Notice that the isolated resistant bacteria contain a very high percent of each mutation. Below is a table describing
the relationship between the number of mutations in these two genes compared to resistance to quinolones where the
percentage is the number of bacteria of each type that have that number of mutations. For example, of the 9 isolates of
antibiotic susceptible bacteria, 55.6% or 5 had no mutations.
Questions
1. Examine the graph from experiment 1.
a. How many times more ampicillin does it take to treat E. coli that has NDM-1? (Hint: Convert the % of
wild type to how many more times ampicillin is needed.)
b. Would taking this much more be reasonable? (Consider that a normal dose is 1 pill.) How many pills would
you have to take?
2. According to experiment 2, how does the number of mutations afect resistance to quinolones?
3. How do you think the mutations in gyrA and parC cause resistance to quinolones? (Hint: Look at the amino
acid numbers and remember that drugs need to bind the target.)
4. Which of the following would be more likely to increase the resistance of bacteria to more than one class of
antibiotics: the mutations in gyrA and parC, or the expression of NDM-1? Why?
5. Explain the order of events concerning the development of antibiotic resistance in a population. (Events [not in
correct order]: Exposure to antibiotics, bacteria population evolution, and random DNA mutations.)
6. As evolution is the change in allele frequency in a population over time …
a. What does a bacteria need to do to infuence the allele frequency in a population?
b. When considering multi-cellular organisms, what kind of genetic changes will not impact evolution?
Instructions
When thinking about evolution, many people assume that it is only something that happened millions of years ago
and therefore is not important now. So, is evolution relevant today?
To explore this issue, you will discuss in groups the economic, environmental, political, and medical issues associated
with antibiotic resistance. Ten, as a class, we will discuss the ideas or solutions that you propose for the growing
problem of antibiotic resistance.
• Form a group containing one of the following: a journalist, a doctor, a politician, and a parent. Te goal of each
group is to compile a chart of the many factors that could infuence antibiotic resistance.
• If you are a doctor or politician or parent:
o Individually examine the graph at the top of your page and look at the axes. What information does the
graph contain? Use this information to write a few sentences about your conclusions.
• If you are the journalist:
o See the chart example to understand how each fact that will be presented by the doctor, politician, or parent
may be composed of medical, political, economic, and environmental factors.
• Work as a group to fll out the chart.
o Take turns reading your conclusions from your graph and the facts at the bottom of the page.
o Decide as a group which factors (medical, political, economic, and environmental) each conclusion represents.
o Have the journalist write that information on the chart.
• After the chart has been completed, discuss as a group the question: How should we reduce antibiotic resistance?
• Pick a member of your group to present results of your discussion to the class.
Graph Conclusions:
Consider
• More than 70% of the bacteria that cause hospital-acquired infections are resistant to at least one of the drugs
most commonly used to treat them.
• People infected with antibiotic-resistant organisms are more likely to have longer and more expensive hospital
stays, increasing the burden on the healthcare system.
• New antibiotics are not proftable to develop. It takes around 500 million dollars and 12-15 years to develop
and get a new antibiotic approved. Once the antibiotic is being used, resistance generally develops in 1-5 years.
Graph Conclusions:
Consider
• In 1950, scientists discovered that low doses of antibiotics make chickens grow faster than normal. Your
constituents are heavily into agriculture and their livelihoods depend upon high yield.
• Reduced antibiotic use may lead to decreased productivity and increased food prices.
• Treating animals with antibiotics allows more animals to be raised on smaller amounts of land than animals
not treated with antibiotics. Environmental lobbyists argue that this treatment is inhumane and leads to greater
antibiotic concentrations in the environment.
sinusitis 50 % 13 mil
Graph Conclusions:
Consider
• Over 50% of patients don’t fnish their prescriptions. Tis allows partially resistant bacteria to live, so that next
time the antibiotic does not kill the bacteria as efectively.
• Body soaps, household cleaners, sponges, and even mattresses and lip-glosses are now packing bacteria-killing
ingredients. Tese products can cause increased antibiotic resistance. Also, these products alter a person’s
microfora (normal bacteria that exist on skin and in digestive tract).
• Parents and patients often demand antibiotics for sickness even if it is unlikely to help. Antibiotics would be
useless for infections caused by viruses for example. But if a doctor does not prescribe the antibiotic, the patient/
parent can go to a diferent doctor. Tere are currently no laws in the United States regulating how doctors
prescribe antibiotics.
Exercise 1
How does antibiotic resistance of bacteria demonstrate various principles of evolution? Make sure to use and underline
the following terms in context: selection, mutation, adaptation, bottleneck, ftness, and allele. Limit your responses to one
short paragraph.
Exercise 2
Where do antibiotics come from? What does their source have to do with evolution? Limit your responses to one or
two paragraphs.
Exercise 3
Write one page on the role of population diversity in evolution. Be sure to address the following questions:
• What is population diversity? (Diferentiate between phenotype and genotype.)
• Why is genetic diversity critical for evolution?
• What would happen to a population or a species if it did not have genetic diversity?
• In detail, how does a population become diverse? (Hint: Explain how mutations occur.)
Cartoon above by Nick D. Kim, doi:10.1371/journal.pbio.0050112.g001, appearing in MacCallum CJ, 2007 Does Medicine without Evolution
Make Sense? PLoS Biol 5(4): e112. doi:10.1371/journal.pbio.0050112
•
Image in the case title block is a colorized 2005 scanning electron micrograph (SEM) depicting numerous clumps of methicillin-resistant
Staphylococcus aureus bacteria, commonly referred to by the acronym, MRSA. Magnifed 2390x. Courtesy of CDC/ Jef Hageman, M.H.S. Tis
public domain image is ID#10047 and available from http://phil.cdc.gov/phil/details.asp.
Case copyright held by the National Center for Case Study Teaching in Science, University at Bufalo, State University of New York.
Originally published July 11, 2011. Please see our usage guidelines, which outline our policy concerning permissible reproduction of this work.