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Antibiotic resistance: the coming plague?




                       QuickTimeª and a
                         decompressor
               are needed to see this picture.
What is an antibiotic?
Are all bacteria threats to human health?
How do antibiotics work?
How do bacteria become resistant?
How does antibiotic resistance spread?
What can be done?
Penicillin - the first documented antibiotic


                                       Discovered by Alexander Fleming in 1929
             QuickTimeª and a
               decompressor
     are needed to see this picture.




                                       Nobel Prize with Florey and Chain, 1945

 Penicillium mold kills
 Staphylococcus and
gram positive bacteria


                                                                       QuickTimeª and a


Resistance was documented
                                                                          decompressor
                                                               are needed to see this picture.




even before penicillin was
widely available for clinical use!
Penicillin is a beta-lactam that inhibits the formation of bacterial
cell walls because it mimics the structure of cell wall components




                                                      penicillin



                 QuickTimeª and a          “R” group can be modified to produce
                                           other antibiotics (methicillin, amoxicillin)
                   decompressor
         are needed to see this picture.




                                                      Bacterial peptidoglycan
Streptomycin
isolated Streptomyces, soil bacterium
discovered by Selman Waksman in 1942
                                                      QuickTimeª and a
                                                        decompressor
                                               are needed to see this picture.



        Effective against gram-
        negative bacteria, including
        Tuberculosis




                                        Works by binding to bacterial
 Nobel Prize in 1952
                                                ribosomes
Vancomycin - drug of last resort
(isolated from soil bacterium)


Glycopeptide that inhibits
cell wall synthesis

                                           QuickTimeª and a

Must be given intravenously                  decompressor
                                   are needed to see this picture.
Good medical practice involves culturing bacteria in patient samples


                                              Antibiotic sensitivity test


                                              Bacteria from patient
                    QuickTimeª and a          create a lawn across an agar
                                              plate
                      decompressor
            are needed to see this picture.




                                              Each disk (black circles)
                                              contains a different
                                              antibiotic
Microbes R us


Number of bacteria on our
body surfaces is ~10x more
than the number of cells in our
bodies


Most inhabit GI tract where
they synthesize some essential
vitamins and amino acids and
process otherwise indigestible
foods


rDNA sequencing identifies
over 70 species, including some
unknown types
Human microbiota are complex
Antibiotics select bacteria with genes that
                confer resistance




                        QuickTimeª and a
                          decompressor
                 are needed to see this picture.




This doesn’t happen when the antibiotic isn’t there
MDR - TB
                                                   Vancomycin-
(Multi-drug resistant)                              resistant

                                 MRSA
                         (Methicillin-resistant)
Antibiotic resistance increases due to:


New mutations (rare process)


Vertical transfer of DNA
Multiplication of existing resistant bacteria


Horizontal (lateral) transfer of DNA
Exchange of DNA between different bacteria
Bacteria are social! They live in complex communities
                                 (biofilms)

                                  Conjugation: a pilus sent out from
                                  one bacterium contacts a second
                                  bacterium, causing a pore to form


                                     Bacteria sense the presence
                                     of other bacteria and
                                     produce molecules that clump
                                     them together


Antibiotic resistance can be transferred between different bacteria
Plasmids can be passed from one bacterium to another
                  through the pilus




  Plasmids: small, circular pieces of DNA that
  replicate independently in bacterial cytoplasm
Both cells contain the plasmid after conjugation is
                     complete
Transformation: Bacteria can pick up pieces of DNA from the
                       environment




                                     Inefficient process
                                     BUT, you only need one
                                     to get many more!


                                     Transformation is widely
                                     used in biotechnology
Plasmid genes encode
proteins that confer
resistance
Vancomycin resistance


Vancomycin no longer            QuickTimeª and a
                                  decompressor
binds to peptidoglycan   are needed to see this picture.
Antibiotic resistance can
also spread in the
environment
Partners in Health has pioneered new strategies for
                     combating MDR-tuberculosis
       Global inequities in health care produce acute situations
                        in hospitals and prisons



                               QuickTimeª and a
                                 decompressor
                        are needed to see this picture.




Abandon strategy based solely on institutionalization
Careful record keeping and detailed analyses of different TB
strains
Home visits from health professionals to insure compliance
with a complicated regimen of drugs
Public health message




                               QuickTimeª and a
                                 decompressor
                        are needed to see this picture.

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5 1

  • 1. Antibiotic resistance: the coming plague? QuickTimeª and a decompressor are needed to see this picture.
  • 2. What is an antibiotic? Are all bacteria threats to human health? How do antibiotics work? How do bacteria become resistant? How does antibiotic resistance spread? What can be done?
  • 3. Penicillin - the first documented antibiotic Discovered by Alexander Fleming in 1929 QuickTimeª and a decompressor are needed to see this picture. Nobel Prize with Florey and Chain, 1945 Penicillium mold kills Staphylococcus and gram positive bacteria QuickTimeª and a Resistance was documented decompressor are needed to see this picture. even before penicillin was widely available for clinical use!
  • 4. Penicillin is a beta-lactam that inhibits the formation of bacterial cell walls because it mimics the structure of cell wall components penicillin QuickTimeª and a “R” group can be modified to produce other antibiotics (methicillin, amoxicillin) decompressor are needed to see this picture. Bacterial peptidoglycan
  • 5. Streptomycin isolated Streptomyces, soil bacterium discovered by Selman Waksman in 1942 QuickTimeª and a decompressor are needed to see this picture. Effective against gram- negative bacteria, including Tuberculosis Works by binding to bacterial Nobel Prize in 1952 ribosomes
  • 6. Vancomycin - drug of last resort (isolated from soil bacterium) Glycopeptide that inhibits cell wall synthesis QuickTimeª and a Must be given intravenously decompressor are needed to see this picture.
  • 7. Good medical practice involves culturing bacteria in patient samples Antibiotic sensitivity test Bacteria from patient QuickTimeª and a create a lawn across an agar plate decompressor are needed to see this picture. Each disk (black circles) contains a different antibiotic
  • 8. Microbes R us Number of bacteria on our body surfaces is ~10x more than the number of cells in our bodies Most inhabit GI tract where they synthesize some essential vitamins and amino acids and process otherwise indigestible foods rDNA sequencing identifies over 70 species, including some unknown types
  • 10. Antibiotics select bacteria with genes that confer resistance QuickTimeª and a decompressor are needed to see this picture. This doesn’t happen when the antibiotic isn’t there
  • 11. MDR - TB Vancomycin- (Multi-drug resistant) resistant MRSA (Methicillin-resistant)
  • 12. Antibiotic resistance increases due to: New mutations (rare process) Vertical transfer of DNA Multiplication of existing resistant bacteria Horizontal (lateral) transfer of DNA Exchange of DNA between different bacteria
  • 13. Bacteria are social! They live in complex communities (biofilms) Conjugation: a pilus sent out from one bacterium contacts a second bacterium, causing a pore to form Bacteria sense the presence of other bacteria and produce molecules that clump them together Antibiotic resistance can be transferred between different bacteria
  • 14. Plasmids can be passed from one bacterium to another through the pilus Plasmids: small, circular pieces of DNA that replicate independently in bacterial cytoplasm
  • 15. Both cells contain the plasmid after conjugation is complete
  • 16. Transformation: Bacteria can pick up pieces of DNA from the environment Inefficient process BUT, you only need one to get many more! Transformation is widely used in biotechnology
  • 17.
  • 18. Plasmid genes encode proteins that confer resistance
  • 19. Vancomycin resistance Vancomycin no longer QuickTimeª and a decompressor binds to peptidoglycan are needed to see this picture.
  • 20. Antibiotic resistance can also spread in the environment
  • 21. Partners in Health has pioneered new strategies for combating MDR-tuberculosis Global inequities in health care produce acute situations in hospitals and prisons QuickTimeª and a decompressor are needed to see this picture. Abandon strategy based solely on institutionalization Careful record keeping and detailed analyses of different TB strains Home visits from health professionals to insure compliance with a complicated regimen of drugs
  • 22. Public health message QuickTimeª and a decompressor are needed to see this picture.