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How did Ehrlich and Fleming contribute to the development of chemotherapy?
- Ehrlich: the "magic bullet" for syphilis
- -any useful drug must be selectively toxic to harm the MO's cells much more than the host's cells
- *MO must have a target that the host does not
- Fleming: discovered that mold let out a product that did not allow MO to grow
- -discovered penicillin
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How did Domagk discover sulfa drugs and why are they not considered an antibiotic?
Domagk: created a red dye called Prontosil which killed bacteria, but no guinea pigs. This became a sulfa drug
* not considered an antibiotic because it is synthetic. instead it is antibmicrobial
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Define Antibiotic
- A chemical that kills or interferes with the growth of microorganisms and is produced by microbes
- -antibiotics have been around forever
- -the MOs that produce the antibiotic must have a resistance to it
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What are some microorganisms that produce medically-useful antibiotics
- Bacillus (soil bacterium): bacitracin
- Streptomyces (soil bacterium): streptomycin
- Penicillin (mold/fungus): penicillin
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What is selective toxicity? Why is this so significant for antibiotics?
- Selective toxicity means that it has a target on the Mo that the host does not have
- -hurts the MO way more than the host
- Fungi, protists, and helminths are eukaryotes so it is harder to be selectively toxic BUT
- -for bacteria, this is great because it has many selectively toxic targets as prokaryotes
(in order to stop a virus, you would have to stop transcription and that harms the host)
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What are the advantages and disadvantages of broad spectrum antibiotics?
- Advantage: you don't need to know the specific MO, your're probably going to kill it
- -this can save some time and some $$$
Disadvantage: you can kill the good stuff too and cause a super infection
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What are the advantages and disadvantages of using a narrow antibiotic?
Advantage: you can kill that specific MO without harming other Flora
Disadvantage: you may pick the wrong one!
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What is a superinfection and how does it occur?
- When a pathogenic/resistant MO takes over!
- -Occurs as a consequence of broad spectrum drug use
- -normal flora is killed while other can thrive
- -->normal flora normally out-competes the others
examples: candidiasis and C. difficile colitis
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What is a "drug resistant bacterial strain"?
A strain of bacteria that does not respond to certain chemotherapy
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What is the difference between innate resistance and acquired resistance?
- Innate Resistance: "expected resistance"
- -humans are innately resistant to antibiotics
- -Gram negative are innately resistant to penicillin
- Acquired resistance: "surprise resistance"
- -Ex: MRSA (Methicillin Resistant Staph Aureus)
- -the concentration of methicillin that kills MRSA is usually too high to put into the patient
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What is the mode of the action for β-Lactam antibiotics?
- β-Lactam molecules bind to and inhibit the enzymes that make peptide crosslinks
- -works in vegetative cells
- -bacteria will form weak peptidoglycan resulting in cell lysis
*better known as the "cillins"
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What is the mode of the action for tetracylines?
- Tetracycline molecules bind to and inhibit ribosomes
- -translation inhibitors: stops protein synthesis
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What is the mode of the action for Quinolones?
- Quinolone molecules bind to and inhibit DNA Gyrase
- -bacterium cannot replicate its DNA
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What is the mode of the action for Trimethoprim and sulfa drugs?
PABA (nutrient)-->Enz 1-->intermediate-->Enz 2--> Folic acid (Essential metabolite needed to build aas and nucleotide synthesis)
- -Sulfa molecules bind to and inhibit Enz 1 molecules
- -Trimethoprim molecules bind to and inhibit Enz 2 molecules
- -Bactrim: TMP + Sulfa in low doses
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What makes β-Lactams selectively toxic?
Animal cells lack the enzymes that make peptide cross links as they do not have cell walls
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What makes Tetracyclines selectively toxic?
Bacterial membranes are tetracyline permeable. Animal cell membranes are tetracycline impermeable
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What makes Quinolones selectively toxic?
Bacterial gyrases have a significantly different structure from animal gyrases
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What makes Trimethoprim and Sulfa drugs selectively toxic?
- Animal cells lack Enz 1 and Enz 2
- -animals get their folic acid in their food, whereas bacteria make it
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What are the 4 common mechanisms of acquired drug resistance in bacteria?
- 1. acquired genes that code for β-lactamases
- -enzymes that destroy β lactam
- 2. acquired genes that code for rapid drug eflux pumps (RDEP)
- -spit the tetracyclines back out of the cell
- 3. acquired genes that code for abnormally tiny porins
- -not permeable to quinolones
- 4. acquired genes that code for mutant Enzyme 1 or 2
- -mutant enzymes work but stop TMP and Sulfa drugs from binding to it
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What are some human practices that have caused populations of antibiotic resistance bacteria to increase?
- -unnecessary prescription of antibiotics
- -failure to take full course of antibiotics
- -use of antibiotics in animal feed
**humans are not the cause or creator of resistance, but definitely aide in making it more common
**the emergence of drug resistance is the inevitable consequence of drug use
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How are humans trying to slow the spread of drug resistance in bacterial populations?
- -Use less antibiotics (only when necessary)
- -less in food products
- - more specific drug use
*by minimizing drug use, non-resistant strains can out compete the resistant ones once more
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