MICROBIOLOGY - ALCAMO LECTURE: CRITERIA FOR PROKARYOTES & EUKARYOTES.
MICROBIOLOGY – ALCAMO
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Transcript of MICROBIOLOGY – ALCAMO
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 infectionsUseless 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 “____________ ____________ ” AntibioticWide 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 post-
surgery 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-the-counter