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Development of resistant Staphylococcus aureus over time
- 1. Development of antibioticresistant Staphylococcus aureus over time Attacks and Defenses Course University of Vermont College of Medicine January 2011 Timothy Plante, MS-IV
- 2. About This is apresentation 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 apresentation 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 atime there was a bacterium. All of his bacteria friends thought he was pretty good looking.
- 5. Once upon atime there was a bacterium. All of his bacteria friends thought he was pretty good looking.
- 6. They would commenton 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 atime 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.
- 8. Here’s staph aureus’nice thick peptidoglycan wall!
- 9. Here he isin his towel returning from the Gram Stain water park! His peptidoglycan layer got darkly stained.
- 10. Look! He’s allpurple! That’s why he’s 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 likesto live on your body with his friends. The best way is in clusters! Skin! In your nares!
- 12. He has akitty named Catalase.
- 13. Catalase is alittle strange
- 14. as she onlyeats hydrogen peroxide H2O2
- 15.
- 16. and only peesout H2O and O2. H2O2
- 17.
- 18.
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- 23.
- 24.
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- 28.
- 29. One day, staphaureus went for a hike and came across some fungus. It was called Penicillum.
- 30. As he gotclose, he started feeling funny. Lets find out why…
- 31.
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- 37.
- 38. And then hedied.
- 39. But for otherstaph aureus bacteria, this wasn’t much of a problem because they didn’t run into penicillium when they were hanging out in the skin or nares. They had a pretty fun life!
- 40. Sometimes they hada little too much fun and would cause infections Like crusty superficial infections of the skin in kids called impetigo
- 41. Sometimes they wouldhang out in food and release cytolytic toxins that make people sick. Food
- 42. Or would sneakinto places where they shouldn’t by breaking down a component of collagen and the extracellular matrix, hyaluronic acid, with hyaluronidase!
- 43. hyaluronidase Or would sneakinto places where they shouldn’t by breaking down a component of collagen and the extracellular matrix, hyaluronic acid, with hyaluronidase!
- 44. hyaluronidase Or would sneakinto places where they shouldn’t by breaking down a component of collagen and the extracellular matrix, hyaluronic acid, with hyaluronidase!
- 45. hyaluronidase Or would sneakinto places where they shouldn’t by breaking down a component of collagen and the extracellular matrix, hyaluronic acid, with hyaluronidase!
- 46. hyaluronidase Or would sneakinto places where they shouldn’t by breaking down a component of collagen and the extracellular matrix, hyaluronic acid, with hyaluronidase!
- 47. hyaluronidase Or would sneakinto places where they shouldn’t by breaking down a component of collagen and the extracellular matrix, hyaluronic acid, with hyaluronidase!
- 48. hyaluronidase Or would sneakinto places where they shouldn’t by breaking down a component of collagen and the extracellular matrix, hyaluronic acid, with hyaluronidase!
- 49. Or would sneakinto places where they shouldn’t by breaking down a component of collagen and the extracellular matrix, hyaluronic acid, with hyaluronidase!
- 50. Or would sneakinto places where they shouldn’t by breaking down a component of collagen and the extracellular matrix, hyaluronic acid, with hyaluronidase!
- 51. Or would sneakinto places where they shouldn’t by breaking down a component of collagen and the extracellular matrix, hyaluronic acid, with hyaluronidase!
- 52. Or would sneakinto places where they shouldn’t by breaking down a component of collagen and the extracellular matrix, hyaluronic acid, with hyaluronidase!
- 53. Or would sneakinto places where they shouldn’t by breaking down a component of collagen and the extracellular matrix, hyaluronic acid, with hyaluronidase!
- 54. Or would sneakinto places where they shouldn’t by breaking down a component of collagen and the extracellular matrix, hyaluronic acid, with hyaluronidase!
- 55. He was verygood at hide and seek whenever red blood cells were around.
- 56. He’d just releasecoagulase and they form a clot around him
- 57. And with justa little staphylokinase, the clot would break up!
- 58. And then justfor fun, he’d blow up the red blood cells.
- 59. And then justfor fun, he’d blow up the red blood cells.
- 60. And then justfor fun, he’d blow up the red blood cells.
- 61. And then justfor fun, he’d blow up the red blood cells.
- 62. Researchers one daywould 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. Beta’s the best! Researchersone 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 anda while a white blood cell would try to pick on him
- 65. And would tryto eat him
- 66. But he’d preventbeing phagocytosed
- 67. With his nicepolysaccharide slime layer and protein-A on his surface.
- 68. Then he’d blowup the white blood cell with leukocidin!
- 69. Then he’d blowup the white blood cell with leukocidin!
- 70. Then he’d blowup the white blood cell with leukocidin!
- 71. Then he’d blowup the white blood cell with leukocidin!
- 72. Then he’d blowup the white blood cell with leukocidin!
- 73. Then he’d blowup the white blood cell with leukocidin!
- 74. T S S When he wasfeeling really mean, he’d release a superantigen toxin T S S
- 75. When he wasfeeling really mean, he’d release a superantigen toxin Like TSS-1 and cause toxic shock syndrome!
- 76. When he wasfeeling really mean, he’d release a superantigen toxin Like TSS-1 and cause toxic shock syndrome! All of the lymphocytes would cause inflammation even though TSS-1 isn’t the antigen they’re supposed to react to!
- 77. When he wasfeeling really mean, he’d release a superantigen toxin Like TSS-1 and cause toxic shock syndrome! All of the lymphocytes would cause inflammation even though TSS-1 isn’t the antigen they’re supposed to react to!
- 78. When he wasfeeling really mean, he’d 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 isn’t the antigen they’re supposed to react to!
- 79. But all inall, as long as he stayed away from the Penicillum fungus, there wasn’t too much to worry about!
- 80. Until one daywhen he was innocently hanging out in a joint having a bit of fun…
- 81. Until one daywhen he was innocently hanging out in a joint having a bit of fun… When he started feeling funny.
- 82.
- 83. But not justhim! His friend causing endocarditis died!
- 84. And his friendcausing cellulitis died!
- 85. And his friendscausing impetigo died!
- 86.
- 87.
- 88. Penicillin! How could thisbe? 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 staphaureus was dying left and right! Anytime they got out of control, they were taken down with some penicillin.
- 90.
- 91.
- 92. Until one day… Onestaph aureus didn’t seem bothered by the penicillin!
- 93.
- 94. Well those arenew! What do they do?
- 95. membrane Peptidoglycan layer O Uh oh,here comes Penicillin!
- 96.
- 97. membrane Peptidoglycan layer O The betalactam ring is broken! This is a beta- lactamase.
- 98.
- 99.
- 100. membrane Peptidoglycan layer And sincethe lactamase has been used, more is produced.
- 101. membrane Peptidoglycan layer And sincethe lactamase has been used, more is produced.
- 102. membrane Peptidoglycan layer And sincethe lactamase has been used, more is produced.
- 103. So this littlestaph aureus is resistant to beta lactam drugs like penicillin and amoxicillin!
- 104. But what aboutthe others?
- 108.
- 109.
- 113. A virus thatinfects bacteria, a bacteriophage!
- 114. A virus thatinfects bacteria, a bacteriophage! And it’s injecting its genome.
- 115. A virus thatinfects bacteria, a bacteriophage! And it’s injecting its genome. Along with the beta- lactamase gene from the resistant staph aureus!
- 116.
- 117. And pretty soonthe bacteriophage spread the resistance to almost all of the staph aureus all over the developed world!
- 118. Resistant staph aureuscan be around with penicillum without worry.
- 119. Resistant staph aureuscan be around with penicillum without worry. He lives wherever he pleases! The penicillin does nothing anymore.
- 120.
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- 127.
- 128. membrane O COOH It’s clavulanate, abeta lactamase inhibitor!
- 129. membrane O COOH It’s clavulanate, abeta 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 thebeta 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. It’s clavulanate, a beta lactamase inhibitor!
- 131. membrane O COOH It destroys thebeta 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. It’s clavulanate, a beta lactamase inhibitor!
- 132. O COOH It destroys thebeta 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. It’s clavulanate, a beta lactamase inhibitor!
- 133. But as longas there are no beta-lactamase inhibitors, they’ll still be resistant to beta-lactam antibiotics, right?
- 134. Wrong. But as longas there are no beta-lactamase inhibitors, they’ll still be resistant to beta-lactam antibiotics, right?
- 135. membrane O COOH What’s this?It looks like penicillin except with a funny new side chain.
- 136. membrane O COOH What’s this?It looks like penicillin except with a funny new side chain. It’s a synthetic penicillin, methicillin (we learned about its cousin nafcillin in class).
- 137. membrane O COOH What’s this?It looks like penicillin except with a funny new side chain. It’s a synthetic penicillin, methicillin (we learned about its cousin nafcillin in class).
- 138. membrane O COOH What’s this?It looks like penicillin except with a funny new side chain. It’s a synthetic penicillin, methicillin (we learned about its cousin nafcillin in class).
- 139. membrane O COOH What’s this?It looks like penicillin except with a funny new side chain. And now the beta lactamase can’t reach the beta lactam ring to do its job. It’s a synthetic penicillin, methicillin (we learned about its cousin nafcillin in class).
- 140. membrane O COOH What’s this?It looks like penicillin except with a funny new side chain. It’s a synthetic penicillin, methicillin (we learned about its cousin nafcillin in class). And now the beta lactamase can’t reach the beta lactam ring to do its job.
- 141. O COOH What’s this?It looks like penicillin except with a funny new side chain. It’s a synthetic penicillin, methicillin (we learned about its cousin nafcillin in class). And now the beta lactamase can’t reach the beta lactam ring to do its job.
- 142. This staph aureuswas taken out by a different drug entirely!
- 143. membrane O COOH Look! Acelphalosporin! It’s a new drug with the structure of a penicillin except...
- 144. membrane O COOH Look! Acelphalosporin! It’s 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! Acelphalosporin! It’s 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! Acelphalosporin! It’s 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! Acelphalosporin! It’s 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! Acelphalosporin! It’s 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! Acelphalosporin! It’s 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! Acelphalosporin! It’s 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! Acelphalosporin! It’s 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 betalactamase no longer fits. The cephalosporin will chop up the wall just like penicillin! Look! A celphalosporin! It’s 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 somestaph 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 somestaph 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 willadd more modifications to make the bacterial weaponry no longer work. O COO O COO
- 156. And bacteria willagain come up with ways to chop up these drugs. And so on. O COO O COO
- 157. After a longenough time, one particular staph aureus underwent a very strange mutation.
- 158. After a longenough time, one particular staph aureus underwent a very strange mutation.
- 159. After a longenough time, one particular staph aureus underwent a very strange mutation.
- 160. Let’s take acloser look… After a long enough time, one particular staph aureus underwent a very strange mutation.
- 161. membrane It looks likethe transpeptidase, also known as the penicillin binding protein, has changed!
- 162. membrane It looks likethe 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 likethe 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, it’s a methicillin resistant staph aureus or MRSA.
- 164. If we wereto look at his DNA, we’d 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 wereto look at his DNA, we’d find that he has something called the MecA gene. It means that all of his offspring will also have this gene.
- 166. If we wereto look at his DNA, we’d find that he has something called the MecA gene. It means that all of his offspring will also have this gene.
- 167. If we wereto look at his DNA, we’d find that he has something called the MecA gene. It means that all of his offspring will also have this gene.
- 168. But the MecAgene slows him down! He’ll be outgrown every time by plain-old methicillin susceptible staph aureus (MSSA).
- 169. But the MecAgene slows him down! He’ll be outgrown every time by plain-old methicillin susceptible staph aureus (MSSA).
- 170. But the MecAgene slows him down! He’ll be outgrown every time by plain-old methicillin susceptible staph aureus (MSSA).
- 171.
- 172. O O COOH Unless thereare antibiotics like methicillin or cephalosporins around.
- 173. Just for thatreason, MRSA loves to live in hospitals!
- 174. So if peopleare in the hospital for long enough, they’ll often get colonized by MRSA. For that, he is known as hospital-acquired MRSA (HA-MRSA).
- 175. But as soonafter they get home, they get recolonized by MSSA.
- 176. And up untilrecently HA-MRSA stayed in and around hospitals.
- 177. And up untilrecently HA-MRSA stayed in and around hospitals. Until one day…
- 178. And up untilrecently HA-MRSA stayed in and around hospitals. Until one day…
- 179. DNA MecA One particular MRSAdeveloped a smaller and more efficient MecA gene.
- 180. And can nowcompete with MSSA out in the community.
- 181. And can nowcompete with MSSA out in the community.
- 182. And can nowcompete with MSSA out in the community.
- 183.
- 184. O O COOH But isstill resistant to the beta lactam drugs!
- 185. Now a goodamount of the population in the community is colonized with this new, competitive MRSA, known as community- acquired MRSA (CA-MRSA).
- 186. Now a goodamount 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 thing’s forsure, Staph aureus and Catalase will be around for a long, long time.
- 188. The end. One thing’sfor sure, Staph aureus and Catalase will be around for a long, long time.