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Objec&ve
1.
Discuss
the
general
history
of

      an&bio&cs
(chemotherapy)

a)  Who
were
some
of
the
scien&sts
who
made

    the
earliest
contribu&ons
to
an&bio&c

    therapy?

b)  What
did
they
discover?

c)  What
were
the
two
earliest
an&bio&cs
used?

d)  What
genus
of
bacteria
produces
the

    majority
of
an&bio&cs?

First
Medical
Applica&on
of
an

               An&bio&c

•  Prontosil

•  A
chemical,
product
of
the
garment
industry
for

   fabric
dyes,
1908

•  Domagk
tested
compounds
from
a
red
dye
on

   preven&ng
mortality
in
mice
infected
with
strep

   or
staph
bacteria,
1930’s,
Prontosil

•  Commercially
available
1935

•  Used
in
WWII,
but
sulfa‐resistant
strains

   emerged

                        hQp://www.silentwall.com/Prontosil.html


•  Awarded
the
prize
1939

•  Prevented
by
the
Nazi
party
from

   accep&ng
un&l
1947

Discovery
of
An&bio&cs

•  Penicillium
chrysogenum
or
notatum,
only

   certain
strains

•  Alexander
Fleming,
1928

  –  Growing
S.
aureus
in
petri
dishes

  –  Le
plates
out
over
a
weekend,
contaminated

     with
fungal
growth

  –  Observed
there
was
a
clearing
around
the
fungal

     growth

  –  Fungus
inhibited
bacterial
growth

  –  Research
fizzled…forgoQen
results

Applica&on
of
Penicillin

•  Before
widespread
availability,
home
prepara&ons
of
fungus‐
   soaked
gauze
for
wounds
–
3,000
years
tradi&on

    –  Not
always
effec&ve,
penicillin
is
strain‐dependent

•  Florey,
Abraham,
Chain
and
Heatley
rediscovered
Fleming’s

   paper

    –  Found
the
most
effec&ve
strain
of
P.
chrysogenum
that

       came
from
a
moldy
cantaloupe
(brought
in
by
Mary
Hunt,

       “Mouldy
Mary”)

•  Raper,
Moyer
and
Coghill

    –  Added
corn
steep
liquor
to
increase
produc&on
of

       penicillin
–
mass
produc&on
became
possible

•  1940’s,
WWII
–
effec&ve
use
to
prevent
amputa&on
and
many

   deaths

Dirt!

•  The
majority
of
commercially
available

   an&bio&cs
come
from
the
genus
of
bacteria,

   Streptomyces

•  Streptomyces
are
filamentous
bacteria
found

   in
the
soil
(and
are
the
component
of
dirt
that

   smell
like
“dirt”)

  –  An&bio&cs
are
secondary
metabolites

  –  Nonessen&al
chemicals
derived
from
primary

     metabolites

  –  Chemicals
toxic
to
compe&ng
species

  –  “bacteria
are
social”




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History of Antibiotics from Fleming to Mass Production

  • 1. Objec&ve
1.
Discuss
the
general
history
of
 an&bio&cs
(chemotherapy)
 a)  Who
were
some
of
the
scien&sts
who
made
 the
earliest
contribu&ons
to
an&bio&c
 therapy?
 b)  What
did
they
discover?
 c)  What
were
the
two
earliest
an&bio&cs
used?
 d)  What
genus
of
bacteria
produces
the
 majority
of
an&bio&cs?

  • 2. First
Medical
Applica&on
of
an
 An&bio&c
 •  Prontosil
 •  A
chemical,
product
of
the
garment
industry
for
 fabric
dyes,
1908
 •  Domagk
tested
compounds
from
a
red
dye
on
 preven&ng
mortality
in
mice
infected
with
strep
 or
staph
bacteria,
1930’s,
Prontosil
 •  Commercially
available
1935
 •  Used
in
WWII,
but
sulfa‐resistant
strains
 emerged
 hQp://www.silentwall.com/Prontosil.html


  • 4. Discovery
of
An&bio&cs
 •  Penicillium
chrysogenum
or
notatum,
only
 certain
strains
 •  Alexander
Fleming,
1928
 –  Growing
S.
aureus
in
petri
dishes
 –  Le
plates
out
over
a
weekend,
contaminated
 with
fungal
growth
 –  Observed
there
was
a
clearing
around
the
fungal
 growth
 –  Fungus
inhibited
bacterial
growth
 –  Research
fizzled…forgoQen
results

  • 5. Applica&on
of
Penicillin
 •  Before
widespread
availability,
home
prepara&ons
of
fungus‐ soaked
gauze
for
wounds
–
3,000
years
tradi&on
 –  Not
always
effec&ve,
penicillin
is
strain‐dependent
 •  Florey,
Abraham,
Chain
and
Heatley
rediscovered
Fleming’s
 paper
 –  Found
the
most
effec&ve
strain
of
P.
chrysogenum
that
 came
from
a
moldy
cantaloupe
(brought
in
by
Mary
Hunt,
 “Mouldy
Mary”)
 •  Raper,
Moyer
and
Coghill
 –  Added
corn
steep
liquor
to
increase
produc&on
of
 penicillin
–
mass
produc&on
became
possible
 •  1940’s,
WWII
–
effec&ve
use
to
prevent
amputa&on
and
many
 deaths

  • 6.
  • 7. Dirt!
 •  The
majority
of
commercially
available
 an&bio&cs
come
from
the
genus
of
bacteria,
 Streptomyces
 •  Streptomyces
are
filamentous
bacteria
found
 in
the
soil
(and
are
the
component
of
dirt
that
 smell
like
“dirt”)
 –  An&bio&cs
are
secondary
metabolites
 –  Nonessen&al
chemicals
derived
from
primary
 metabolites
 –  Chemicals
toxic
to
compe&ng
species
 –  “bacteria
are
social”