MBIO 1010 Study Guide - Final Guide: Vancomycin, Hyaluronidase, Xeroderma
31 May 2018
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MBIO 1010 - Summer 2018
79
UNIT 6 – ANTIMICROBIAL DRUGS AND RESISTANCE
Antimicrobial Drugs
- Compounds that kill or inhibit the growth of microorganisms in a human or animal
- Must exhibit Selective Toxicity
o Looking for chemicals that will harm other microorganisms without harming
humans/animals (hosts) that are needing treatment
o Damage to pathogen, no damage to the host
- Can be bactericidal (kill) or bacteriostatic (prevent from growing)
o Neither one is better over the other, both work just as effect as the other
Spectrum of Activity
- Range of microbes affected by the drug
- Narrow Spectrum
o Affects only microbes within a limited functional group
§ Ex. Penicillin G works against Gram positive bacteria
• Will not work against Gram negative because of outer membrane
- Very Narrow Spectrum
o Affects only a very specific group
§ Ex. Isoniazid works only against mycobacteria
• In this case, the isoniazid works only on mycolic acid which can only be
found on mycobacteria
- Broad Spectrum
o Works against a wide range of microbes from a single domain
§ Ex. Tetraglycine works against both gram positive and gram negative bacteria
Synthetic Antibacterial Drugs
- Anything drug not created by a microorganism, or has gone through altercations
- Growth factor analogues
o Structurally similar to growth factors, interfere with metabolism
o Important for biosynthesis
o Won’t be able to grow without growth factors
§ Ex. Sulfa drugs (sulfanilamide)
• Structurally similar to PABA (vitamin, precursor for folic acid)
• Inhibits growth of bacteria by interfering with folic acid synthesis
• Without folic acid, there is no folate
• Does not hurt us since we cannot turn PABA into folate, we have to
mechanically eat folate through leafy green vegetables
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- Quinalones (Fluoroquinolones)
o Interfere with DNA replication in bacteria
o Only one that contains fluorine
§ Ex. Ciprofloxacin
• Powerful antibacterial drug
• Targets the “supercoiling” of DNA
by attacking an enzyme only in
bacteria, DNA gyrase through
selective toxicity
o Broad spectrum and extremely effective
o Antibiotic resistance develops quickly
Natural Antibacterial Drugs
- Antibiotic
o Antimicrobial agents produced by other microorganisms
o Usually produced by a fungus or Streptomyces (bacteria thinking it’s a fungus)
§ Ex. Penicillin
• Produced by the bread mold in Penicillium
§ Ex. Streptomycin
• Produced by Streptomyces griseus
o Thousands of antibiotics have been discovered, but less than 1% are clinically useful
§ Discovery of new antibiotics are at a low since they do not make a lot of money
o Most antibiotics in use today are semi-synthetic
§ Natural antibiotic was modified to change its properties
• Ex. Penicillin G is acid labile and narrow spectrum
Ø Must be injected since it would burn through stomach and can
only work on Gram positive bacteria
• Solution: Ampicillin
Ø Acid stable and has a broad spectrum
b
-lactam Antibiotics
- Penicillin
o Inhibit bacterial cell wall synthesis
§ Excellent selective toxicity (since
humans have no peptidoglycan)
o
b
-lactam ring
§ Active structural component
§ Binds to periplasmic proteins (penicillin
binding proteins)
§ Blocks final step in peptidoglycan synthesis
(cross-linking)
§ Antimicrobial will die without lactam ring
o Antibiotic resistance
§ Some bacteria produce
b
-lactamase
• Enzyme that cleaves the b-lactam ring
• Ultimately destroys the antibiotic
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- Semi-synthetic penicillin
o Small changes to penicillin side chains result in altered activity
§ It’s the acetyl groups that cause them to be more or less synthetic
o Ex. Ampicillin
§ Broad spectrum and acid stable
o Ex. Methicillin
§ Resistant to b-lactamase
§ Designed to fight multiple antibiotic resistant S. aureus
• This resulted in methicillin resistant S. aureus (MRSA)
• After the release of methicillin, the S. aureus figured its way round it and
created MRSA which turns out to be resistant to methicillin and
everything else S. aureus is resistant to (which is almost everything)
- Cephalosporins
o Structurally different from penicillins,
but include a the b-lactam ring
o Broader spectrum than penicillins
o More resistant to the b-lactamases
o Used to treat infections by penicillin
resistant Gram-negative bacteria
Aminoglycosides
- Amino sugars linked by glyosidic bonds
- Target 30S subunit of the ribosome
o Blocks protein synthesis
- Has broad spectrum
o Particularly useful against Gram negative bacteria
- Some toxicity towards humans
o We have 70S ribosomes in our mitochondria
§ 30S subunits are found there which can
explain why it can be toxic to us
o Known as “Last resort antibiotics”
o Very strong and can be toxic, but last resort to
infections if it has not responded to any other drugs
- Ex. Streptomycin
o Produced by Streptomyces griseus
Macrolides
- Structure based on the lactone ring
o Substitutions to the ring make macrolides with different properties
- Ex. Erythromycin
o Produced by Streptomyces erythreus
o Targets 50S subunit of the ribosome
o Partially blocks protein synthesis
o Leads to preferential synthesis of some proteins
o Narrow spectrum against Gram positives
§ Large hydrophobic molecule does not
penetrate most Gram negative outer membranes
o Can be used on people who are allergic to penicillin
Document Summary
Compounds that kill or inhibit the growth of microorganisms in a human or animal. Must exhibit selective toxicity: looking for chemicals that will harm other microorganisms without harming humans/animals (hosts) that are needing treatment, damage to pathogen, no damage to the host. Can be bactericidal (kill) or bacteriostatic (prevent from growing: neither one is better over the other, both work just as effect as the other. Range of microbes affected by the drug. Narrow spectrum: affects only microbes within a limited functional group. Penicillin g works against gram positive bacteria: will not work against gram negative because of outer membrane. Very narrow spectrum: affects only a very specific group. In this case, the isoniazid works only on mycolic acid which can only be found on mycobacteria. Broad spectrum: works against a wide range of microbes from a single domain. Tetraglycine works against both gram positive and gram negative bacteria.
