Microbio Lecture 14
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- Selective Toxicity
- kill or inhibit pathogen while damaging host as little as possible
- Degree of selective toxicity depends on (3)
-
- Therapeutic dose
- Toxic dose
- Therapeutic index - Therapeutic dose:
- drug level required for clinical treatment of a particular infection
- Toxic dose
- drug level when undesirable effects produced
- Most drugs are what spectrum?
- Narrow
- Disadvantage of Broad spectrum:
- could kill good bacteria
- Examples of broad spectrum drugs
-
Neomycin: effective against G+/-
Zeocin: anti bacterial and anti fungal
Sulfonamides: antibacterial, fungal, protozoal - Difference between bactericidal and bacteriostatic
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bactericidal: bacteria can't grow
bacteriostatic: inhibits growth and slows it down, buys time for your immune system to get rid of it - Origin of antibiotics (3)
- Natural, Synthetic, Semi-synthetic
- Natural
-
produced by living organism
Streptomyces: streptomycin, chlortetrarcycline, erythromycin
Penicillium: penicillin - Synthetic:
-
manufactured from nonnatural products
-sulfonamides, trimethoprim - Semisynthetic
-
Chemical modification of natural antibiotics
- penicillin derivatives: ampicillin, carbenicillin, methicillin - 5 mechs of Antimicrobial action:
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Protein synthesis
Nucleic acid
Cell wall
Cell membrane
Metabolic reactions - Protein synthesis drugs
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aminoglycosides
chloramphenicol
tetracyclines
erythromycin
clindamycin
spectinomycin - Nucleic acid drugs
-
rifampin
nalidixic acid
metronidazole - Cell wall drugs
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penicillin
cephalosporins
vancomycin
bacitracin
cefoxitin - Cell membrane drugs
- polymyxins
- Metabolic reaction drugs
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sulfa drugs
isoniazid
trimethoprim - Polymyxin B
-
cell membrane disruption- binds cell membrane components
Natural: bacillus
Effective against: G- (pseudomonas aeruginosa)
Triple Antibiotic Ointment w/ neomycin (broad spectrum) and bacitracin (g+)
if ingested: can cause numbness in extremities,kidney damage, respiratory arrest
low selective toxicity - Sulfonamides
-
Synthetic
- Sulfanilimide is analog of PABA (p-aminobenzoic acid)
-inhibits folic acid production b/c competes with PABA for active site DIHYDROPTERATE SYNTHETASE
- bacterias make folic acid not humans
-high therapeutic index, but 5% allergic - Examples of sulfonamides: (2)
-
sulfamethoxazole
sulfisoxazole - Inhibition of DNA synthesis are due to:
-
Quinolones - Nalidixic acid
Nalidixic acid selectively inhibits DNA gyrase (enzyme req'd for dna replication)
-effective against certain urinary infections
- bad for kids, pregnant women b/c affects cartilage
- therefore made FLUOROQUINOLONES
improvment over nalidixic acid
penetrate tissue better
more broad spectrum - Examples of Fluroquinolones and what do fluoroquinolones do?
-
Ciprofloxacin, norfloxacin
they inhibit DNA synthesis by messing with DNA gyrase (enzyme needed for DNA replication) -
Inhibition of RNA synthesis
what is used, the origin, used for what, side effects -
-Rifampin inhibits DNA dependent RNA polymerase in bacteria
-semi-synthetic
- for: tuberculosis, leprosy, protectin again meningitis
- side effect: turn body secretions red/orange -
Penicillins
what do they do, origin, problems, what is common in all of them -
-inhibit transpeptidation -->cell wall synthesis; results in osmotic lysis
- semi synthetic dervatives: ampicillin- more acid stable
- problem: allergic reactions/ growing resistance
- Beta lactam nucleus is common in all of them -
Cephalosporins
what do they do?, examples, origin -
cell wall synthesis inhibitor has beta lactam ring like penicillin
- cephalein (Keflex), cephalothin
- useful alternative to penicillin (allergy and resistance) -
Bacitracin
what does it do? - interferes with bactoprenol- carrier that transports peptidoglycan subunits to cell wall
- Drugs used for inhibition of protein synthesis (4)
-
tetracyclines
aminoglycosides
macrolides
chloramphenicol -
Tetracyclines
origin, use, problems, used for? -
- broad spectrum, semi-synthetic, from streptomyces
- four benzene rings
- inhibit protein synthesis by binding 30S ribosomal unit - inhibits binding of tRNA to ribosome
- problem for kids and pregnant women with bone formation - yellow teeth
- used for rickettsial, chlamydial diseases -
Examples of Tetracyclines:
2 natural
4 semisynthetic -
from streptomyces:
- chlortetracycline
- oxytetracycline
semisynthetic:
- doxycycline
- tetracycline
- methacycline
- minocycline -
Aminoglycosides
origin (2), what do they do, problems -
- amino groups bound to glycosides (carbs)
- origin: Streptomyces and Micromonospora purpurea
- prevent reading of mRNA by irreversibly binding to ribosome
- TOXIC: deafness, renal damage, loss of balance -
Examples of aminoglycosides
3 from Streptomyces
1 from Micromonospora purpurea -
strept: streptomycin, kanamycin, neomycin
micro: gentamicin -
Macrolides
what does it do, used for, examples -
-Broad spectrum: g+/-
-12-22 carbon lactone ring
- inhibits peptide chain elongation
- used to treat Legionnaire's disease: legonella pneumophilla
- erythromycin, clindamycin, azithromycin - Chloramphenicol
-
last resort drug
- binds ribosome and blocks peptide bond formation to inhibit protein synthesis
- natural: streptomyces
- broad spectrum (bact, small bact, fungi)
- low therapeutic index; cause aplastic anemia by preventing hemoglobin being incorporated into RBC, Gray syndrome: toxic reactino, breakdown of cardiovascular system - Mechanisms of Resistance for Microorganisms (3 ways)
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1. prevent entrance of drug
2. pump drug out of cell
3. inactivation of drug - Example of Preventing entrance of drug
-
-Mycobacterium has mycolic acid in cell wall which is impermeable to most drugs
- use of isoniazid (isonicotinic acid hydrazide) inhibits production of mycolic acid - Inactivation of drug through chemical modification
-
- use penicillinase to inactivate beta lactam ring
- type of resistance can be encoded by PLASMIDS and transferred via conjugation and transformation - 2 reasons why microbial drug resistance is increasing
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1. indiscriminate use of chemotherapeutics
2. transmission of R factors between microbes (r factors transferred b/n unrelated strains through conjugation and transformation)