Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Biochemistry wikipedia , lookup
Endomembrane system wikipedia , lookup
Epitranscriptome wikipedia , lookup
Cell-penetrating peptide wikipedia , lookup
Peptide synthesis wikipedia , lookup
Biosynthesis wikipedia , lookup
Amino acid synthesis wikipedia , lookup
Clinical neurochemistry wikipedia , lookup
List of types of proteins wikipedia , lookup
Artificial gene synthesis wikipedia , lookup
De novo protein synthesis theory of memory formation wikipedia , lookup
Chapter 10 Controlling microbial growth in the body: Antimicrobials • Like disinfectants antimicrobial drugs act by killing or inhibiting the growth of microorganisms. • Antimicrobial drugs must act within the body and show _______________________. Antimicrobial Drugs • Chemotherapy: the use of drugs to treat a disease • Antimicrobial drugs: interfere with the growth of microbes within a host • Selective toxicity: killing harmful microbes without damaging the host Representative Sources of Antibiotics Insert Table 20.1 Spectrum of Activity • ________________: Antibiotic affects a large number of Gram-positive or Gram-negative bacteria • ________________: Affective against a small range of organisms – Penicillin G affects Gram-positive bacteria but very few Gram-negatives The Spectrum of Activity of Antibiotics and Other Antimicrobial Drugs Spectrum of Activity – Use of broad spectrum drugs also destroy ______ _______________ – Survivors may become _______________ – Yeast infections may arise from the over growth of Candida albicans • _______________ – Term is also applied to growth of a target pathogen that has developed resistance to the antibiotic – Antibiotic resistant strain replaces the original sensitive strain and the infection continues • Antibiotics are only effective against ________ infections • ________(flu) and ______________are _____ infections therefore antibiotics are ineffective! Inhibition of Cell Wall Synthesis – • Most common agents prevent cross-linkage of NAM subunits • Beta-lactams are most prominent in this group – Functional groups are beta-lactam rings – Beta-lactams bind to enzymes that cross-link NAM subunits • Bacteria have weakened cell walls and eventually lyse Inhibition or degrading bacterial cell walls. N-acetylglucosamine (NAG) N-acetylmuramic acid (NAM) Side-chain amino acid Cross-bridge amino acid Tetrapeptide side chain Peptide cross-bridge NAM Peptide bond Carbohydrate “backbone” Structure of peptidoglycan in gram-positive bacteria . Inhibition or degrading bacterial cell walls. • Penicillin's • Cephalosporin's • Vancomycin The inhibition of bacterial cell synthesis by penicillin. Rod-shaped bacterium before penicillin. The bacterial cell lysing as penicillin weakens the cell wall. • One of the most successful groups of antibiotics targets the synthesis of bacterial cell walls; why does the antibiotic not affect the mammalian cell? The inhibition of protein synthesis by antibiotics. Protein synthesis site Growing polypeptide Tunnel Growing polypeptide 50S 5′ Chloramphenicol Binds to 50S portion and inhibits formation of peptide bond 30S mRNA 50S portion 3′ Three-dimensional detail of the protein synthesis site showing the 30S and 50S subunit portions of the 70S prokaryotic ribosome Protein synthesis site tRNA Messenger RNA Streptomycin Changes shape of 30S portion, causing code on mRNA to be read incorrectly 30S portion 70S prokaryotic ribosome Translation Direction of ribosome movement Tetracyclines Interfere with attachment of tRNA to mRNA–ribosome complex Diagram indicating the different points at which chloramphenicol, the tetracyclines, and streptomycin exert their activities Inhibitors of Protein Synthesis – Prokaryotic ribosomes are 70S (30S and 50S) – Eukaryotic ribosomes are 80S (40S and 60S) – Drugs can selectively target translation – Mitochondria of animals and humans contain 70S ribosomes • Can be harmful Inhibitors of Protein Synthesis • Chloramphenicol – Broad spectrum • Binds 50S subunit; inhibits peptide bond formation Inhibitors of Protein Synthesis • Aminoglycosides – Streptomycin • Broad spectrum – Change shape of 30S subunit • Can have fatally toxic effects on Kidneys Inhibitors of Protein Synthesis • Tetracyclines – Broad spectrum • Interfere with tRNA attachment – Side effects? Should Children take tetracycline? • Children may experience a brown discoloration of teeth • Pregnant women may cause liver damage – Most common antibiotic added to animal feed • Use results in significantly faster weight gain Inhibition of nucleic acid replication and transcription Inhibitors of Nucleic Acid Synthesis – Several drugs block DNA replication or mRNA transcription – Drugs often affect both eukaryotic and prokaryotic cells – Not normally used to treat infections – Used in research and perhaps to slow cancer cell replication Inhibitors of Nucleic Acid Synthesis • Rifamycin – Inhibits RNA synthesis – Antituberculosis Injury to the plasma membrane of a yeast cell caused by an antifungal drug. Injury to the Plasma Membrane • Some drugs form channel through cytoplasmic membrane and damage its integrity • Polymyxin B – Topical – Combined with bacitracin and neomycin in over-the-counter preparation Inhibiting the Synthesis of Essential Metabolites: Antimetabolics – Antimetabolic agents can be effective when metabolic processes of pathogen and host differ – Sulfonamides (sulfa drugs) Inhibit folic acid synthesis Broad spectrum Inhibiting the Synthesis of Essential Metabolites: Antimetabolics Figure 5.7bc Enzyme inhibitors. Action of Enzyme Inhibitors Competitive inhibitor Altered active site Noncompetitive inhibitor Allosteric site Major Action Modes of Antimicrobial Drugs. 1. Inhibition of cell wall synthesis: penicillins, 2. Inhibition of protein synthesis: chloramphenicol, cephalosporins, bacitracin, vancomycin erythryomycin, tetracyclines, streptomycin DNA mRNA Transcription Protein Translation Replication Enzyme 4. Injury to plasma membrane: polymyxin B 5. Inhibition of essential metabolite synthesis: sulfanimide, trimethoprim 3. Inhibition of nucleic acid replication and transcription: quinolones, rifampin Clinical Considerations in Prescribing Antimicrobial Drugs • Routes of Administration – Topical application of drug for external infections – Oral route requires no needles and is selfadministered – Intramuscular administration delivers drug via needle into muscle – Intravenous administration delivers drug directly to bloodstream Figure 10.13 The effect of route of administration on blood levels of a chemotherapeutic agent Administration method Relative concentration of drug in blood Oral Intramuscular (IM) Continuous intravenous (IV) Time (hours) Clinical Considerations in Prescribing Antimicrobial Drugs • Safety and Side Effects – Toxicity • Cause of many adverse reactions poorly understood • Drugs may be toxic to kidneys, liver, or nerves • Consideration needed when prescribing drugs to pregnant women – Allergies • Allergic reactions are rare but may be life threatening • Anaphylactic shock Figure 10.14 Some side effects resulting from toxicity of antimicrobial agents-overview Black hairy tongue caused by antiprotozoan drug metronidazole (Flagyl) Temporary and Harmless! Discoloration and damage to tooth enamel caused by tetracycline Resistance to Antimicrobial Drugs • The Development of Resistance in Populations • Some pathogens are naturally resistant • Resistance by bacteria acquired in two ways • New mutations of chromosomal genes • Acquisition of R-plasmids via transformation, transduction, and conjugation Antibiotic Resistance • Misuse of antibiotics selects for resistance mutants • Misuse includes: – – – – – Resistance plasmid S. enterica after conjugation S. enterica Cephalosporin-resistance in E. coli transferred by conjugation to Salmonella enterica in the intestinal tracts of turkeys. E. coli Clinical Focus Antibiotics in Animal Feed Linked to Human Disease, Figure A. Antibiotic Resistance – At least 6 mechanisms of microbial resistance 1. 2. 3. 4. 5. 6. Effects of Combinations of Drugs • __________occurs when the effect of two drugs together is greater than the effect of either alone • ___________occurs when the effect of two drugs together is less than the effect of either alone Figure 20.23 An example of synergism between two different antibiotics. Area of synergistic inhibition, clear Disk with antibiotic amoxicillin-clavulanic acid Area of growth, cloudy Disk with antibiotic aztreonam