Control of Bacterial Growth
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Control of Bacterial Control of Bacterial GrowthGrowth Antibiotics / Chemotherapy
– History– Properties– Testing– Spectrum of Antimicrobial Action– Modes of Action– Survey of Drugs
Antibiotics Antibiotics
History– Quinine for malaria– Willow bark for treating fever– Paul Ehrlich - staining of bacteria led
to ideas for chemotherapy– Fleming (1928) observed the effect of
Penicillium of on Staphylococcus– Flory & Chain (1940) developed
penicillin and clinically tested it
AntibioticsAntibiotics Peruvian Indians - treat fevers and reduce shivering with
cinchona bark Use " Peruvian bark" was first recorded by the Jesuits in
1633 Countess Anna del Chinchón. was cured of the ague (a
name for malaria the time) in 1638 The Dutch bought the Bolivian seeds from Charles Ledger,
a British botanist, planted them in Java, and came to monopolize the world's supply of quinine for close to 100 years.
A formal chemical synthesis was accomplished in 1944 by American chemists Woodward and W.E. Doering
Since then, several more efficient quinine syntheses have been achieved, but none of them can compete in economic terms with isolation of the alkaloid from natural sources.
Malaria resistant to synthetic but less so to natural The first synthetic organic dye, mauveine, was discovered
by William Henry Perkin in 1856 while he was attempting to synthesize quinine.
AntibioticsAntibiotics 1928 – Fleming discovers penicillin and
isolates a crude form of the chemical 1930’s - Florey and Chain further refine
chemical methods for isolation of penicillin from culture filtrates
WWII – work transferred to Peoria IL – development of submerged culture processes
Post WWII – additional markets for penicillin leads to resistance
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Properties– Selective toxicity (e.g. sulfanilamide
mimics PABA in folic acid synthesis)– Sources
»Microorganisms»Synthetic agents»Plants
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Testing– Broth dilution– Agar dilution– Disc diffusion
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Broth dilution – MIC - minimal inhibitory concentration
» smallest concentration that stops growth» Successive dilutions inoculated with same
number bacteria» Turbidity measure when compared to control
(could also do dilutions & plate counts)
– MBC - minimal bactericidal concentration» Concentration of antibiotic where cell number is
reduced significantly» Will typically be a higher concentration than MIC
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Agar dilution– Dilute drug into agar at varying
concentrations– Can test multiple species of bacteria– Not very quantitative
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Disc-Diffusion– Discs with known
concentrations of antibiotics seeded onto “lawn” of bacteria
– Zone of clearing around disk a measure of effectiveness of antibiotic
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Spectrum of Antimicrobial Activity– Selectively toxic drugs; uses
differences between prokaryotic and eukaryotic cells
– Broad spectrum – affect both G+ and G-
– Antibiotic effect, e.g. penicillin and Candida albicans
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Modes of Action– Bactericidal vs. Bacteriostatic– Cell Wall– Protein Synthesis– Plasma membrane– Nucleic Acid Synthesis– Essential Metabolites
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Bactericidal vs. Bacteriostatic– Bactericidal - kills– Bacteriostatic - inhibits growth but
once removed growth can resume
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Inhibition of Cell Wall Synthesis– Uniqueness of bacterial cell wall– Prevent peptidoglycan synthesis or
peptide cross-linking from forming– Penicillins & cephalosporins
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Inhibition of Protein Synthesis– Bacterial protein synthesis
significantly different than eukaryotic e.g. 70S vs. 80S ribosome or elongation & termination factors
– Amyloglycosides (streptomycin and gentamicin)
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Injury of Plasma Membrane– Alteration in permeability– Interference with required
consituents, e.g. sterols in fungal lipid membranes
– Polymixin B (bacteria)– Amphotericin B or miconazole
(fungal)
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Essential Metabolites– Para-aminobenzoic acid is an
essential cofactor used by bacteria to synthesize folic acid (a vitamin that functions as a coenzyme in the synthesis of nucleic acid precursors)
– animals ingest folic acid– Sulfanilamide is an analog of PABA
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Inhibition of Nucleic Acid Synthesis– Nucleic acid synthesis especially
mRNA and DNA– Rifampin and quinolones– Limited utility because of RNA’s and
DNA’s essential role in both prokaryotic and eukaryotic cells
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Survey of Drugs - Cell Wall Synthesis– Penicillins (G, V)– Semisynthetic penicillins (Ampicillin)– Monobactams– Vancomycin - Glycopeptide topical– Cephalosporins– Bacitracin - bacterial origin; topical use– Isoniazid - tuberculosis– Ethambutol - tuberculosis
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Survey of Drugs - Protein Synthesis– Amyloglycosides (Streptomycin,
neomycin Gentamicin)– Tetracyclines - Bacteriostatic– Chloramphenicol – Macrolides - Erythromycin -
Bacteriostatic
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Survey of Drugs - Plasma Membrane– Polymyxin B - topical; works against
G-
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Survey of Drugs - Nucleic Acids– Rifampin– Quinolones– Fluorquinolones
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Survey of Drugs - Essential Metabolites– Sulfonamides
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