A module covering the development of antibiotic resistance in Staphylococcus aureus including the development of MRSA or methicillin resistant staph aureus.
Development of resistant Staphylococcus aureus over time
1. Development of antibiotic resistant
Staphylococcus aureus over time
Attacks and Defenses Course
University of Vermont College of Medicine
January 2011
Timothy Plante, MS-IV
2. About
This is a presentation that I made my senior year in medical
school for an infectious disease course at the University of
Vermont College of Medicine. It was picked up by BoingBoing.net
and was viewed by quite a few folks on the internet.
3. About
This is a presentation that I made my senior year in medical
school for an infectious disease course at the University of
Vermont College of Medicine. It was picked up by BoingBoing.net
and was viewed by quite a few folks on the internet.
I had a lot of fun making this. Enjoy!
4. Once upon a time there was a bacterium. All of his bacteria friends
thought he was pretty good looking.
5. Once upon a time there was a bacterium. All of his bacteria friends
thought he was pretty good looking.
6. They would comment on how nice his gold color was.
Once upon a time there was a bacterium. All of his bacteria friends
thought he was pretty good looking.
7. Once upon a time there was a bacterium. All of his bacteria friends
thought he was pretty good looking.
And because of that, he was named staph aureus as auro is the
Latin word for gold.
They would comment on how nice his gold color was.
9. Here he is in his towel returning from the Gram Stain water park!
His peptidoglycan layer got darkly stained.
10. Look! Heās all purple! Thatās why heās called gram positive.
Here he is in his towel returning from the Gram Stain water park!
His peptidoglycan layer got darkly stained.
11. Staph aureus likes to live on your body
with his friends. The best way is in
clusters!
Skin!
In your
nares!
39. But for other staph aureus bacteria, this wasnāt much of a problem
because they didnāt run into penicillium when they were hanging
out in the skin or nares. They had a pretty fun life!
40. Sometimes they had a little too much fun and would cause infections
Like crusty superficial
infections of the skin in
kids called impetigo
41. Sometimes they would hang out in food and release cytolytic toxins that
make people sick.
Food
42. Or would sneak into places where they shouldnāt by breaking down a
component of collagen and the extracellular matrix, hyaluronic acid, with
hyaluronidase!
43. hyaluronidase
Or would sneak into places where they shouldnāt by breaking down a
component of collagen and the extracellular matrix, hyaluronic acid, with
hyaluronidase!
44. hyaluronidase
Or would sneak into places where they shouldnāt by breaking down a
component of collagen and the extracellular matrix, hyaluronic acid, with
hyaluronidase!
45. hyaluronidase
Or would sneak into places where they shouldnāt by breaking down a
component of collagen and the extracellular matrix, hyaluronic acid, with
hyaluronidase!
46. hyaluronidase
Or would sneak into places where they shouldnāt by breaking down a
component of collagen and the extracellular matrix, hyaluronic acid, with
hyaluronidase!
47. hyaluronidase
Or would sneak into places where they shouldnāt by breaking down a
component of collagen and the extracellular matrix, hyaluronic acid, with
hyaluronidase!
48. hyaluronidase
Or would sneak into places where they shouldnāt by breaking down a
component of collagen and the extracellular matrix, hyaluronic acid, with
hyaluronidase!
49. Or would sneak into places where they shouldnāt by breaking down a
component of collagen and the extracellular matrix, hyaluronic acid, with
hyaluronidase!
50. Or would sneak into places where they shouldnāt by breaking down a
component of collagen and the extracellular matrix, hyaluronic acid, with
hyaluronidase!
51. Or would sneak into places where they shouldnāt by breaking down a
component of collagen and the extracellular matrix, hyaluronic acid, with
hyaluronidase!
52. Or would sneak into places where they shouldnāt by breaking down a
component of collagen and the extracellular matrix, hyaluronic acid, with
hyaluronidase!
53. Or would sneak into places where they shouldnāt by breaking down a
component of collagen and the extracellular matrix, hyaluronic acid, with
hyaluronidase!
54. Or would sneak into places where they shouldnāt by breaking down a
component of collagen and the extracellular matrix, hyaluronic acid, with
hyaluronidase!
55. He was very good at hide and seek whenever red
blood cells were around.
57. And with just a little staphylokinase, the clot would break up!
58. And then just for fun, heād blow up the red blood cells.
59. And then just for fun, heād blow up the red blood cells.
60. And then just for fun, heād blow up the red blood cells.
61. And then just for fun, heād blow up the red blood cells.
62. Researchers one day would find that he and his friends strep
pyogenes and strep agalactidae did this so well on a blood
agar plate that they would be able to be identified by their
complete hemolysis, a pattern we call beta hemolysis!
63. Betaās the best!
Researchers one day would find that he and his friends strep
pyogenes and strep agalactidae did this so well on a blood
agar plate that they would be able to be identified by their
complete hemolysis, a pattern we call beta hemolysis!
64. Every once and a while a white blood
cell would try to pick on him
74. T
S
S
When he was feeling really
mean, heād release a
superantigen toxin
T
S
S
75. When he was feeling really
mean, heād release a
superantigen toxin
Like TSS-1 and cause toxic
shock syndrome!
76. When he was feeling really
mean, heād release a
superantigen toxin
Like TSS-1 and cause toxic
shock syndrome!
All of the lymphocytes would
cause inflammation even
though TSS-1 isnāt the antigen
theyāre supposed to react to!
77. When he was feeling really
mean, heād release a
superantigen toxin
Like TSS-1 and cause toxic
shock syndrome!
All of the lymphocytes would
cause inflammation even
though TSS-1 isnāt the antigen
theyāre supposed to react to!
78. When he was feeling really
mean, heād release a
superantigen toxin
And people would get fever,
low blood pressure, and a
blanching rash that looked like
a sunburn!
Like TSS-1 and cause toxic
shock syndrome!
All of the lymphocytes would
cause inflammation even
though TSS-1 isnāt the antigen
theyāre supposed to react to!
79. But all in all, as long as he stayed
away from the Penicillum fungus,
there wasnāt too much to worry
about!
80. Until one day when he was
innocently hanging out in a joint
having a bit of funā¦
81. Until one day when he was
innocently hanging out in a joint
having a bit of funā¦
When he started feeling funny.
88. Penicillin!
How could this be?
It seems someone figured out
how to extract the active
compound from the penicillum
fungus and make it to a drug!
O COOH
R
89. So now staph aureus was dying left and right! Anytime
they got out of control, they were taken down with
some penicillin.
113. A virus that infects bacteria, a bacteriophage!
114. A virus that infects bacteria, a bacteriophage!
And itās injecting its genome.
115. A virus that infects bacteria, a bacteriophage!
And itās injecting its genome.
Along with the beta-
lactamase gene from the
resistant staph aureus!
129. membrane
O
COOH
Itās clavulanate, a beta lactamase inhibitor!
It destroys the beta lactamase with its
suicide beta lactam ring. It does not
trigger increased production of beta
lactamase!
130. membrane
O
COOH
It destroys the beta lactamase with its
suicide beta lactam ring. It does not
trigger increased production of beta
lactamase!
COOH
And now a penicillin analogue like
amoxicillin can come in and do its job.
Itās clavulanate, a beta lactamase inhibitor!
131. membrane
O
COOH
It destroys the beta lactamase with its
suicide beta lactam ring. It does not
trigger increased production of beta
lactamase!
COOH
And now a penicillin analogue like
amoxicillin can come in and do its job.
Itās clavulanate, a beta lactamase inhibitor!
132. O
COOH
It destroys the beta lactamase with its
suicide beta lactam ring. It does not
trigger increased production of beta
lactamase!
COOH
And now a penicillin analogue like
amoxicillin can come in and do its job.
Itās clavulanate, a beta lactamase inhibitor!
133. But as long as there are no beta-lactamase inhibitors, theyāll still be
resistant to beta-lactam antibiotics, right?
134. Wrong.
But as long as there are no beta-lactamase inhibitors, theyāll still be
resistant to beta-lactam antibiotics, right?
136. membrane
O COOH
Whatās this? It looks like penicillin
except with a funny new side chain.
Itās a synthetic penicillin, methicillin (we
learned about its cousin nafcillin in
class).
137. membrane
O COOH
Whatās this? It looks like penicillin
except with a funny new side chain.
Itās a synthetic penicillin, methicillin (we
learned about its cousin nafcillin in
class).
138. membrane
O COOH
Whatās this? It looks like penicillin
except with a funny new side chain.
Itās a synthetic penicillin, methicillin (we
learned about its cousin nafcillin in
class).
139. membrane
O COOH
Whatās this? It looks like penicillin
except with a funny new side chain.
And now the beta lactamase canāt
reach the beta lactam ring to do its
job.
Itās a synthetic penicillin, methicillin (we
learned about its cousin nafcillin in
class).
140. membrane
O COOH
Whatās this? It looks like penicillin
except with a funny new side chain.
Itās a synthetic penicillin, methicillin (we
learned about its cousin nafcillin in
class).
And now the beta lactamase canāt
reach the beta lactam ring to do its
job.
141. O COOH
Whatās this? It looks like penicillin
except with a funny new side chain.
Itās a synthetic penicillin, methicillin (we
learned about its cousin nafcillin in
class).
And now the beta lactamase canāt
reach the beta lactam ring to do its
job.
143. membrane
O COOH
Look! A celphalosporin! Itās a new drug with
the structure of a penicillin except...
144. membrane
O COOH
Look! A celphalosporin! Itās a new drug with
the structure of a penicillin except...
It has one more carbon. Look, a six-
carbon ring!
145. membrane
O COOH
Look! A celphalosporin! Itās a new drug with
the structure of a penicillin except...
Along with its hydrogen atoms.
It has one more carbon. Look, a six-
carbon ring!
HH
146. membrane
O COOH
Look! A celphalosporin! Itās a new drug with
the structure of a penicillin except...
It has one more carbon. Look, a six-
carbon ring!
HH
Along with its hydrogen atoms.
147. membrane
O COOH
Look! A celphalosporin! Itās a new drug with
the structure of a penicillin except...
It has one more carbon. Look, a six-
carbon ring!
HH
Along with its hydrogen atoms.
148. membrane
O COOH
Look! A celphalosporin! Itās a new drug with
the structure of a penicillin except...
It has one more carbon. Look, a six-
carbon ring!
The beta lactamase no longer fits. The cephalosporin
will chop up the wall just like penicillin!
HH
Along with its hydrogen atoms.
149. membrane
O COOH
Look! A celphalosporin! Itās a new drug with
the structure of a penicillin except...
It has one more carbon. Look, a six-
carbon ring!
The beta lactamase no longer fits. The cephalosporin
will chop up the wall just like penicillin!
HH
Along with its hydrogen atoms.
150. membrane
O COOH
Look! A celphalosporin! Itās a new drug with
the structure of a penicillin except...
It has one more carbon. Look, a six-
carbon ring!
The beta lactamase no longer fits. The cephalosporin
will chop up the wall just like penicillin!
Along with its hydrogen atoms.
151. membrane
O COOH
Look! A celphalosporin! Itās a new drug with
the structure of a penicillin except...
It has one more carbon. Look, a six-
carbon ring!
The beta lactamase no longer fits. The cephalosporin
will chop up the wall just like penicillin!
Along with its hydrogen atoms.
152. O COOH
The beta lactamase no longer fits. The cephalosporin
will chop up the wall just like penicillin!
Look! A celphalosporin! Itās a new drug with
the structure of a penicillin except...
It has one more carbon. Look, a six-
carbon ring!
Along with its hydrogen atoms.
153. Over time some staph aureus bacteria have developed new things
like the beta lactamases
that will chop up
synthetic penicillins
like methicillin or
nafcillin
O COO
154. Over time some staph aureus bacteria have developed new things
like the beta lactamases
that will chop up
synthetic penicillins
like methicillin or
nafcillin
or the cephalosporins.
O COO
O COO
155. So researchers will add more
modifications to make the bacterial
weaponry no longer work.
O COO
O COO
156. And bacteria will again come up
with ways to chop up these drugs.
And so on.
O COO
O COO
157. After a long enough time, one particular staph aureus underwent a
very strange mutation.
158. After a long enough time, one particular staph aureus underwent a
very strange mutation.
159. After a long enough time, one particular staph aureus underwent a
very strange mutation.
160. Letās take a closer lookā¦
After a long enough time, one particular staph aureus underwent a
very strange mutation.
161. membrane
It looks like the transpeptidase, also known as the
penicillin binding protein, has changed!
162. membrane
It looks like the transpeptidase, also known as the
penicillin binding protein, has changed!
O
O COOH
Now cephalosporins and synthetic penicillins like
methicillin have nothing to attack.
163. membrane
It looks like the transpeptidase, also known as the
penicillin binding protein, has changed!
O
O COOH
Now cephalosporins and synthetic penicillins like
methicillin have nothing to attack.
And because of that, itās a methicillin
resistant staph aureus or MRSA.
164. If we were to look at his DNA, weād find that he
has something called the MecA gene.
DNA
MecA
It means that all of his offspring will also have
this gene.
165. If we were to look at his DNA, weād find that he
has something called the MecA gene.
It means that all of his offspring will also have
this gene.
166. If we were to look at his DNA, weād find that he
has something called the MecA gene.
It means that all of his offspring will also have
this gene.
167. If we were to look at his DNA, weād find that he
has something called the MecA gene.
It means that all of his offspring will also have
this gene.
168. But the MecA gene slows him down!
Heāll be outgrown every time by plain-old methicillin
susceptible staph aureus (MSSA).
169. But the MecA gene slows him down!
Heāll be outgrown every time by plain-old methicillin
susceptible staph aureus (MSSA).
170. But the MecA gene slows him down!
Heāll be outgrown every time by plain-old methicillin
susceptible staph aureus (MSSA).
173. Just for that reason, MRSA loves to live in hospitals!
174. So if people are in the hospital for long enough, theyāll often get
colonized by MRSA. For that, he is known as hospital-acquired
MRSA (HA-MRSA).
175. But as soon after they get home, they get recolonized by MSSA.
176. And up until recently HA-MRSA stayed in and around hospitals.
177. And up until recently HA-MRSA stayed in and around hospitals.
Until one dayā¦
178. And up until recently HA-MRSA stayed in and around hospitals.
Until one dayā¦
185. Now a good amount of the population in the community is
colonized with this new, competitive MRSA, known as community-
acquired MRSA (CA-MRSA).
186. Now a good amount of the population in the community is
colonized with this new, competitive MRSA, known as community-
acquired MRSA (CA-MRSA).
There are a few classes of other antibiotics out there which work
on other bacterial targets to beat HA-MRSA and CA-MRSA.
Resistance against these drugs is slowly but surely emerging.
187. One thingās for sure, Staph aureus and Catalase will be around for a long, long time.
188. The end.
One thingās for sure, Staph aureus and Catalase will be around for a long, long time.
