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MICROBIOLOGY

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MICROBIOLOGY ALCAMO LECTURE: Chemotherapeutic Agents and Antibiotics – PowerPoint PPT presentation

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Title: MICROBIOLOGY


1
MICROBIOLOGY ALCAMO
  • LECTURE
  • Chemotherapeutic Agents and Antibiotics

2
Chemotherapeutic Agents and Antibiotics
  • For centuries, doctors thought that drastic
    measures were necessary to save a patient from
    infectious disease
  • Purges and bloodlettings
  • Large doses of chemicals
  • Ice water baths
  • Starvation
  • These treatments probably made a bad situation
    worse

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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 doctors job
    to diagnose disease, explain it to the family,
    and sit by caring for the patient

5
Chemotherapeutic Agents and Antibiotics
  • Late 1800s germ
  • theory of disease
  • 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 killed many

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Chemotherapeutic Agents and Antibiotics
  • 1940s chemotherapeutic agents and antibiotics
    were discovered
  • Doctors learned that they could kill bacteria in
    the body without harming the body itself
  • Doctors were altering the course of disease which
    made a dramatic change in the world

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Chemotherapeutic Agents Antibiotics
  • Must be more harmful to MO than host cells
  • Chemotherapy only helps the immune system to
    control the infection
  • The immune system ultimately stops MOs

14
Chemotherapeutic Agents
  • Produced in lab, inorganic chemicals
  • Sulfur, Arsenic, Quinine, Nicotinic Acid
  • Still major medical applications
  • Can be quite toxic to patient

15
Antibiotics
  • Originally Chemical produced by an MO which
    inhibits growth of other MOs
  • Now synthesized in labs, Organic Chem

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Chemotherapeutic Agents Antibiotics
  • Have anti-metabolite mechanisms
  • Select for specific MO according to which life
    process you need to disrupt
  • Protein synthesis
  • Cell Wall structure
  • Cell membrane structure
  • RNA or DNA synthesis
  • Chemical reactions

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History of Chemotherapy
  • Paul Ehrlich worked with stains
  • and dyes and found out they had antimicrobial
    properties
  • Collaborated with Sahachiro Hata
  • to produce Salvarsan 1st chemotherapeutic
    drug (cured syphilis)
  • Problems
  • Local reaction at injection site
  • Church wanted syphilis to be a deterrent to
    immoral behavior

20
History of Chemotherapy
  • For the next 20 years, German scientists kept
    testing dyes for antimicrobial properties
  • Gerhard Domagk tested prontosil dye on his own
    daughter when she became ill with septicemia and
    she recovered

21
Sulfa Drugs
  • It was determined that the
  • active ingredient in prontosil
  • is sulfanilimide
  • In 1940, D.D. Woods and E.M. Fildes proposed a
    mechanism of action for sulfa drugs
  • It showed how they could interfere with bacterial
    metabolism without damaging host tissues

22
Competitive Inhibition
  • Bacteria need folic acid to produce nucleic acids
    (DNA and RNA)
  • Bacteria have an enzyme to make folic acid they
    cant get folic acid from environment like we do
  • This enzyme joins PABA with 2 other components to
    make folic acid
  • Sulfanilimide looks like PABA and enzyme will
    bind to it instead of PABA

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Sulfa Drugs
  • Bactrim
  • Sulfamethoxazole
  • Used for urinary tract infections and pneumonia
  • Gantrisin
  • Sulfisoxazole
  • Used for vaginal infections, conjunctivitis and
    toxoplasmosis

25
Antibiotics
  • Word means against life
  • Chemical products or derivatives of certain
    organisms that are inhibitory to other organisms
  • How did organisms gain the
  • ability to produce antibiotics?
  • Random genetic mutation
  • Evolutionary advantage

26
Antibiotics
  • Mainstay for help with bacterial infections.
    Used for some fungal and protozoal
    infectionsUseless on viruses (2ndary Bact Inf)
  • Usually safe/effective, some patients dangerously
    hypersensitive

27
Alexander Fleming
  • Discovered antibiotics
  • One of his agar plates
  • containing staphylococci
  • became contaminated with a green mold
  • He noticed the staphylococci didnt grow near the
    mold
  • He identified the mold as a species of
    Penicillium and he named its substance penicillin

28
Zone of Inhibition
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Penicillin
  • Isolated from a fungus - Penicillium
  • First antibiotic, 1940s
  • Interferes with cell wall synthesis
  • Effective against G MOsFew G- with massive
    doses
  • Cillins a very large family of drugs

30
This bacterium is lysing because an antibiotic
disrupted its cell wall. Why doesnt the
antibiotic lyse human cells?
31
Disadvantages of Penicillin
  • 1. Anaphylaxis or allergy
  • Swelling of the eyes or wrists
  • Flushed or itchy skin, hives
  • Shortness of breath
  • 2. Penicillin-resistant bacteria
  • Produce penicillinase, an enzyme that converts
    penicillin into a useless compound
  • Use too many antibiotics natural selection of
    antibiotic resistant bacteria

32
Semi-synthetic Penicillins
  • In the 1950s the beta-lactam nucleus of the
    penicillin molecule was identified and
    synthesized
  • New penicillins were
  • created by attaching
  • different groups
  • to this nucleus
  • Ampicillin
  • Amoxicillin

33
Cephalosporin
  • Isolated from a fungus - Cephalosporium
  • Interferes with cell wall synthesis
  • Similar to Penicillin can be used in allergic
    persons and with resistant MOs
  • Interferes with some
  • G and some G- MOs

34
Streptomycin
  • Isolated from a filamentous (mold-like) soil
    bacteria - Streptomyces
  • Attaches to ribosomes, blocks messenger RNA
  • Carefully used, toxic side effects (deafness)
  • Mycins a very large family of drugs
  • Neosporin contains
  • Neomycin

35
Chloramphenicol
  • Streptomyces 2nd family of drugsOriginal Prod
    Chloromycetin
  • 1st Broad Spectrum AntibioticWide variety of
    G and G- MOs
  • Interferes with protein
  • synthesis, ribosomes
  • blocked from mRNA

36
Tetracycline
  • Broad spectrum antibiotics
  • Can be taken orally and were used widely in the
    1950s and 1960s
  • Overused, so normal flora was eliminated from the
    intestines
  • Then fungi (Candida albicans) flourished and
    antifungal antibiotics had to be taken
  • Also caused gray-brown tooth discoloration

37
Antimicrobial Drugs
  • Chemotherapy The use of drugs to treat a disease
  • Antimicrobial drugs Interfere with the growth of
    microbes within a host
  • Antibiotic A substance produced by a microbe
    that, in small amounts, inhibits another microbe
  • Selective toxicity A drug that kills harmful
    microbes without damaging the host

38
The Action of Antimicrobial Drugs
  • Bactericidal
  • Kill microbes directly
  • Bacteriostatic
  • Prevent microbes from growing

39
Antibiotic Assays
  • 1. Tube dilution method determines the smallest
    amount of antibiotic necessary to inhibit a test
    organism
  • Prepare a set of tubes with different
    concentrations of an antibiotic
  • The tubes are inoculated with the test organism,
    incubated and examined for growth
  • Extent of growth gets lower with increasing
    concentration of antibiotic
  • When growth fails to occur you have reached the
    minimum inhibitory concentration (MIC)

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Antibiotic Assays
  • 2. Agar or disk diffusion method operates on
    the principle that antibiotics will diffuse from
    a paper disk into agar medium containing test
    organisms
  • Inhibition is observed as a failure of an
    organism to grow in the region of the antibiotic

42
Kirby-Bauer Test
  • 1. Pour agar into plate and inoculate with test
    organism
  • 2. Apply paper disks containing known
    concentrations of antibiotics to the surface
  • 3. Incubate plate
  • 4. Compare diameters of zones of inhibition to a
    standard table to determine if test organism is
    susceptible
  • If organism is susceptible, it will be killed
    in patients blood stream if experimental
    concentration of antibiotic is reached

43
The Disk-Diffusion Method
44
Antibiotic Resistance and Abuse
  • During past 25 years, a large
  • of bacterial species have evolved with
    resistance to drugs and antibiotics
  • Resistant 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 antibiotics are now hard to
    treat
  • Bacterial pneumonia, strep throat, gonorrhea

45
Antibiotic Resistance and Abuse
  • How do MOs acquire resistance?
  • Production of enzymes capable of destroying
    antibiotic (penicillinase)
  • Changes in permeability of cell wall
  • Resistance to drugs activity by bypassing a
    normal metabolic pathway and creating an altered
    one (new way to produce folic acid)

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Antibiotic Resistance and Abuse
  • Antibiotic resistance
  • may develop
  • Normally - mutation
  • From doctors prescribing too many antibiotics
    forced evolution
  • From hospitals using too high doses of
    post-surgery antibiotics forced evolution
  • From livestock feeds which contain 40 of all
    antibiotics produced in U.S. forced evolution

48
Antibiotic Resistance and Abuse
  • Can resistance be transferred??
  • Researchers have transferred 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 disease and death

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Antibiotic Resistance and Abuse
  • Antibiotics have been known as miracle drugs
    they are overworked miracles
  • Suggestions have been made to control their use
    as strictly as narcotics are controlled
  • But, antibiotics are abused in 3rd world
    countries where they are sold over-the-counter

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