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. Tetrapeptide side chain N-acetylglucosamine (NAG) N-acetylmuramic acid (NAM) Peptide cross-bridge Side-chain amino acid Cross-bridge amino acid NAM Peptide bond Carbohydrate “backbone” NAG 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?

Protein synthesis site 70S prokaryotic ribosome 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 50S portion 3′ mRNA 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 30S portion Direction of ribosome movement Streptomycin Tetracyclines 70S prokaryotic ribosome Changes shape of 30S portion, causing code on mRNA to be read incorrectly Interfere with attachment of tRNA to mRNA–ribosome complex Translation 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

Action of Enzyme Inhibitors 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, cephalosporins, bacitracin, vancomycin 2. Inhibition of protein synthesis: chloramphenicol, erythryomycin, tetracyclines, streptomycin DNA mRNA Protein Transcription 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 self-administered Intramuscular administration delivers drug via needle into muscle Intravenous administration delivers drug directly to bloodstream 29

Administration method Figure 10.13 The effect of route of administration on blood levels of a chemotherapeutic agent Administration method Oral Intramuscular (IM) Relative concentration of drug in blood 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 31

Black hairy tongue caused by antiprotozoan drug metronidazole (Flagyl) 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:

Clinical Focus Antibiotics in Animal Feed Linked to Human Disease, Figure A. Cephalosporin-resistance in E. coli transferred by conjugation to Salmonella enterica in the intestinal tracts of turkeys. after conjugation S. enterica S. enterica E. coli Resistance plasmid

Antibiotic Resistance At least 6 mechanisms of microbial resistance

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

Area of synergistic inhibition, clear Area of growth, cloudy Figure 20.23 An example of synergism between two different antibiotics. Area of synergistic inhibition, clear Area of growth, cloudy Disk with antibiotic amoxicillin-clavulanic acid Disk with antibiotic aztreonam