MICROBIOLOGY – ALCAMO
LECTURE:
Chemotherapeutic Agents
and
Antibiotics
Chemotherapeutic Agents
and Antibiotics
• For centuries, doctors thought that drastic
measures were necessary to save a patient
from infectious disease:
– ____________ and ____________
– Large doses of chemicals
– Ice water baths
– ____________
– These treatments probably made a bad situation
worse
Chemotherapeutic Agents
and Antibiotics
• In 1825, doctors in Boston and London wanted
to see what would happen if these treatments
were not given
• They found that no treatment at all was better
• For the next 60 years it became the doctor’s
job to ________________________, explain it
to the family, and sit by caring for the patient
Chemotherapeutic Agents
and Antibiotics
• Late 1800’s – ____________
• ________________________
• Doctors understood
where disease comes
from but could do little
• Tuberculosis killed 1 of every 7 people that died
• Streptococcal heart valve disease, pneumonia,
and meningitis ____________
Chemotherapeutic Agents
and Antibiotics
• 1940’s – chemotherapeutic agents and
____________ were discovered
• Doctor’s learned that they could kill
____________ in the body without harming
the body itself
• Doctors were altering the course of
____________ which made a dramatic change
in the world
Chemotherapeutic Agents &
Antibiotics
• Must be more ____________ to MO than host
cells
• ____________ only helps the immune system
to control the infection
• The immune system ultimately stops MOs
Chemotherapeutic Agents
•
•
•
•
Produced in lab, inorganic chemicals
Sulfur, Arsenic, Quinine, Nicotinic Acid
Still major medical applications
Can be quite ____________ to patient
Antibiotics
• Originally: Chemical produced by an MO which
____________ ____________of other MOs
• Now synthesized in labs, Organic Chem
Chemotherapeutic Agents &
Antibiotics
• Have ____________ ____________
mechanisms
• Select for specific MO according to which life
process you need to disrupt:
– ____________ ____________
– Cell Wall structure
– ___________ ____________ ____________
– RNA or DNA synthesis
– Chemical ____________
History of Chemotherapy
• Paul ____________ – worked with stains and
dyes and found out they had antimicrobial
properties
• Collaborated with Sahachiro Hata
to produce Salvarsan – 1st chemotherapeutic
drug (___________ )
• Problems:
– Local reaction at injection site
– Church wanted ____________ to be a deterrent
to immoral behavior
History of Chemotherapy
• For the next 20 years, German scientists kept
testing dyes for ____________ ____________
• Gerhard Domagk tested prontosil dye on his
own daughter when she became ill with
____________ and she recovered
Sulfa Drugs
• It was determined that the
active ingredient in prontosil
is ____________
• In 1940, D.D. Woods and E.M. Fildes proposed
a mechanism of action for ____________
____________
• It showed how they could interfere with
____________ ____________ without
damaging host tissues
Competitive Inhibition
• Bacteria need folic acid to produce nucleic acids
(____________________ )
• Bacteria have an ____________ to make folic acid –
they can’t get folic acid from ____________ like we
do
• This ____________ joins PABA with 2 other
components to make folic acid
• Sulfanilimide looks like PABA and ____________ will
bind to it instead of PABA
Sulfa Drugs
• ____________ :
– Sulfamethoxazole
– Used for urinary tract infections and pneumonia
• ____________ :
– Sulfisoxazole
– Used for vaginal infections, conjunctivitis and
toxoplasmosis
Antibiotics
• Word means “___________ _________ ”
• Chemical products or derivatives of certain
organisms that are ____________ to other
organisms
• How did organisms gain the
ability to produce __________?
– Random genetic mutation
– Evolutionary advantage
Antibiotics
• Mainstay for help with ____________
____________ . Used for some fungal and
protozoal infections
Useless on ____________ (2ndary Bact Inf)
• Usually ____________ / ____________, some
patients dangerously hypersensitive
Alexander Fleming
• Discovered ____________
• One of his agar plates
containing staphylococci
became contaminated with a green mold
• He noticed the staphylococci didn’t __________
____________ ___________
• He identified the mold as a species of
____________ and he named its substance
penicillin
Zone of Inhibition
Penicillin
• Isolated from a fungus - ____________
• First antibiotic, 1940’s
• Interferes with cell wall
synthesis
• Effective against G+ MOs
Few G- with massive doses
• “____________ : a very large family
of drugs
This bacterium is
lysing because an
antibiotic disrupted
its cell wall. Why
doesn’t the
antibiotic lyse
human cells?
Disadvantages of Penicillin
• 1. ____________ or allergy
– Swelling of the eyes or wrists
– Flushed or itchy skin, hives
– Shortness of breath
• 2. ____________ ____________ bacteria
– Produce ____________ , an enzyme that converts
penicillin into a useless compound
– Use too many ____________ – natural selection
of antibiotic resistant bacteria
Semi-synthetic Penicillins
• In the 1950’s the beta-lactam nucleus of the
____________ molecule was identified and
synthesized
• New ____________
were created by attaching
different groups
to this nucleus:
____________
____________
Cephalosporin
• Isolated from a ____________ - Cephalosporium
• Interferes with ____________ ___________
• Similar to ____________ – can be used in allergic
persons and with resistant MOs
• Interferes with some
G+ and some G- MOs
Streptomycin
• Isolated from a filamentous (mold-like) soil
bacteria - ____________ ____________
• Attaches to ____________ , blocks messenger
RNA
• Carefully used, toxic side effects (____________ )
• “____________ ” a very large
family of drugs
– Neosporin contains
Neomycin
Chloramphenicol
• Streptomyces’ 2nd family of drugs:
Original Prod: Chloromycetin
• 1st “____________ ____________ ” Antibiotic
Wide variety of G+
and G- MOs
• Interferes with protein
synthesis, ____________
blocked from mRNA
Tetracycline
• ____________ ____________ antibiotics
• Can be taken orally and were used widely in the
1950’s and 1960’s
• Overused, so __________ ________was
eliminated from the intestines
• Then ____________ (Candida albicans)
flourished and antifungal antibiotics had to be
taken
• Also caused gray-brown tooth ____________
Antimicrobial Drugs
• ____________ : The use of drugs to treat a
disease
• ____________ ____________ : Interfere with
the growth of microbes within a host
• ____________ : A substance produced by a
microbe that, in small amounts, inhibits another
microbe
• ____________ ____________ : A drug that kills
harmful microbes without damaging the host
The Action of Antimicrobial Drugs
• ____________
– Kill microbes directly
• ____________
– Prevent microbes from growing
Antibiotic Assays
• 1. ____________ ____________ ____________ –
determines the smallest amount of antibiotic
necessary to inhibit a test organism
– Prepare a set of tubes with different ____________ of an
antibiotic
– The tubes are ____________ with the test organism,
incubated and examined for growth
– Extent of ____________ gets lower with increasing
concentration of antibiotic
– When growth ____________ to occur – you have reached
the minimum inhibitory concentration (MIC)
Antibiotic Assays
• 2. Agar or disk ____________ ____________
– operates on the principle that antibiotics will
diffuse from a paper disk into agar medium
containing test organisms
– ____________ ____________ as a failure of an
organism to grow in the region of the antibiotic
Kirby-Bauer Test
• 1. ____________ ____________ into plate and
inoculate with test organism
• 2. ____________ ____________ ____________
containing known concentrations of antibiotics to the
surface
• 3. ____________ plate
• 4. ____________ ____________ of zones of
inhibition to a standard table to determine if test
organism is susceptible
**If organism is susceptible, it will be killed in patient’s
blood stream if experimental concentration of
antibiotic is reached
The Disk-Diffusion Method
Antibiotic Resistance
and Abuse
• During past 25 years, a large #
of bacterial species have evolved with
____________________________________
• ____________ organisms are responsible for human
diseases in:
– Intestines, lungs, skin, urinary tract
• Common diseases that used to be easy to treat with
a single dose of ____________ are now hard to
treat:
– Bacterial pneumonia, strep throat, gonorrhea
Antibiotic Resistance and Abuse
• How do MOs ____________ ____________ ?:
– Production of ____________ capable of
destroying antibiotic (penicillinase)
– Changes in ____________ of cell wall
– ____________ to drug’s activity by bypassing a
normal metabolic pathway and creating an altered
one (new way to produce folic acid)
Antibiotic Resistance
and Abuse
• ____________ ____________
may develop:
– Normally - mutation
– From doctors prescribing too many antibiotics –
forced evolution
– From hospitals using too high doses of postsurgery antibiotics – forced evolution
– From livestock feeds which contain 40% of all
antibiotics produced in U.S. – forced evolution
Antibiotic Resistance and Abuse
Can resistance be transferred??
• Researchers ____________ ____________
antibiotic resistance genes from one bacterial
species to another using plasmids
• There is potential for the transfer of antibiotic
resistance from a harmless bacterium to a
pathogenic bacterium
• Result – ____________ ____________
Antibiotic Resistance and Abuse
• ____________ have been known as miracle
drugs – they are overworked miracles
• Suggestions have been made to
____________ their use as strictly as narcotics
are controlled
• But, antibiotics are ____________ in 3rd world
countries where they are sold over-thecounter