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
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Nobel Prize with Florey and Chain, 1945
Penicillium mold kills
Staphylococcus and
gram positive bacteria
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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
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other antibiotics (methicillin, amoxicillin)
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Bacterial peptidoglycan
5. Streptomycin
isolated Streptomyces, soil bacterium
discovered by Selman Waksman in 1942
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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
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7. Good medical practice involves culturing bacteria in patient samples
Antibiotic sensitivity test
Bacteria from patient
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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
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This doesn’t happen when the antibiotic isn’t there
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
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
21. Partners in Health has pioneered new strategies for
combating MDR-tuberculosis
Global inequities in health care produce acute situations
in hospitals and prisons
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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