Lecture #16: Chemotherapeutic Agents I Flashcards
Antibiotics are for Chemical Warfare
Produced by one soil organism to deter the growth of another. Competition for space in the soil.
Used to say they were produced by fungi. Now some of those fungi have been discovered to be bacteria that resemble fungi, Actinomycetes (High G + C). Blurred the nice distinction.
Effective against bacteria.
Antibiotics Source
Bacteria? Fungi? It’s both. Original drugs came from fungi. Penicillin and Streptomycin from Penicillium and Streptomyces (now a fungus-like bacterium). Common topical ointment from Bacillus.
Bacitracin
a mixture of related cyclic polypeptides produced by organisms of the licheniformis group of Bacillus subtilis var Tracy, isolation of which was first reported in 1945.
As a toxic and difficult-to-use antibiotic, bacitracin does not work well orally. However, it is very effective topically, and is a common ingredient of eye and skin antibiotic preparations. Its action is on gram-positive cell walls.
Selective Toxicity
Either targets the bacterium or more strongly affects it vs. host.
At Best - AB only affects the target. Single out a unique process or structure.
Next best- Major effect on pathogen and minor effect on host.
Spectrum
Range of bacterial types affected.
Narrow Spectrum Drugs – one type (types can be whole groups). Gram +, Gram –, Mycobacterium.
Broad Spectrum Drugs – one type and some of another. Not ‘all bacteria.’ Gram + and some Gram -.
Nature of the Drugs We Use
Most are natural, just purified. Penicillin, Cephalosporin.
Some are natural form then modified to increase effectiveness (i.e., alter a side group). Semi-synthetic. Ampicillin, Methacillin.
Some are totally synthetic. Cipro(floxacin), Chloramphenicol.
Kirby-Bauer Assay System
Standard Method to Assess Drug Sensitivity. Basic way to test for sensitivity. Can be used to determine correct amount of drug to be administered against the strain of pathogen present.
Disk diffusion test. Freshly grown bacteria are used to inoculate the entire surface of a Mueller-Hinton agar plate. After the agar surface has dried for five minutes, the appropriate antibiotic disks are placed on it.
After 16-18 hours of incubation, the diameters of the zones of inhibition are measured to the nearest millimeter.
Competitive Inhibitors
Look-alikes for specific substrates. Enzyme will add in the drug instead of the correct substrate, make some ineffective compound or cell won’t get compound it needs.
Sulfa drugs inserted instead of correct substrate in the making of folic acid. Specific. Eucaryotes can’t make folic acid (lack enzymes) and must get it from their food. Bacteria make it. Unique process targeted.
Drugs That Target Cell Wall Biosynthesis
Penicillins, Ampicillin, and Cephalosporins. Most selective drugs.
Drugs That Target Protein Synthesis
Streptomycin, Erythromycin, Chloramphenicol, Tetracycline.
Drug That Targets Nucleic Acid Synthesis
Quinolones
Drug That Targets Cell Membranes
Polymixins (act like detergents). Least selective drug type.
Penicillium chrysogenum
‘Gold making’- makes color of the media gold.
The dark bands are sporangia, and this ascomycetous fungus is reproductive.
Common in the soil and rots fruits; oranges, melons. Although Fleming originally discovered its AB action in culture, a growth on a canteloup eventually led to a higher production alternative.
Cell Wall Biosynthesis
Penicillins and Cephalosporins. Have an active ring, β-lactam ring. Interferes with cross-linking of proteins in cell wall. Cells susceptible to lysis by osmotic change.
Microbes defend themselves from beta-lactam action with beta-lactamases. Build-up in a biofilm.
Inhibit transpeptidation enzymes involved in cross-linking the polysaccharide chains of the bacterial cell wall peptidoglycan. Activate cell wall lytic enzymes.
Vancomycin
Prevent transpeptidation of peptidoglycan subunits by binding D-Ala-D-Ala amino acids at the end of peptide side chains. Thus it has a different binding site than that of the penicillins.
