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Chemotherapy
Use of chemicals to treat disease
Antimicrobial
Compound that kills or inhibits microorganisms
Antibiotic
Natural compound made by a microorganism that kills or inhibits other microorganisms
Synthetic antimicrobial
Antimicrobial made completely in the laboratory
Semisynthetic antimicrobial
Natural antimicrobial chemically modified in the laboratory
Selective toxicity
Ability of a drug to harm the pathogen more than the host
Magic bullet
Drug that targets a pathogen without harming the host
Paul Ehrlich
Scientist associated with the magic bullet concept
Alexander Fleming
Discovered penicillin in 1928
Penicillin
Antibiotic discovered by Alexander Fleming that targets bacterial cell wall synthesis
Dorothy Hodgkin
Helped determine chemical structures of natural products such as penicillin
Selman Waksman
Discovered important antibiotics from Streptomyces
Streptomyces
Soil actinomycete genus that produces many medically important antibiotics
Streptomycin
Antibiotic from Streptomyces that was important for treating tuberculosis
John Mueller and Jane Hinton
Developed Mueller-Hinton agar
Mueller-Hinton agar
Medium used for Kirby-Bauer disk diffusion testing
Spectrum of activity
Range of microbes affected by an antimicrobial
Narrow-spectrum antimicrobial
Drug that affects only a few specific types of bacteria
Broad-spectrum antimicrobial
Drug that affects many Gram-positive and Gram-negative bacteria
Narrow vs broad spectrum
Narrow affects few bacteria, broad affects many types
Broad-spectrum risk
Can disrupt normal microbiota and lead to superinfection
Superinfection
Secondary infection that occurs after normal microbiota are reduced
Bacteriostatic
Inhibits bacterial growth without directly killing bacteria
Bactericidal
Kills bacteria
Bacteriostatic vs bactericidal
Bacteriostatic inhibits growth, bactericidal kills cells
Synergism
Two drugs together work better than either drug alone
Antagonism
Two drugs together work less effectively than either drug alone
Synergism vs antagonism
Synergism increases drug effect, antagonism decreases drug effect
Kirby-Bauer test
Disk diffusion test used to determine antimicrobial susceptibility
Zone of inhibition
Clear area around an antimicrobial disk where bacteria did not grow
Large zone of inhibition
Bacteria are more likely susceptible to the drug
No zone of inhibition
Bacteria are likely resistant to the drug
Susceptible
Microbe is inhibited by the antimicrobial
Resistant
Microbe is not effectively inhibited by the antimicrobial
Cell wall synthesis inhibitors
Drugs that block peptidoglycan formation
Beta-lactams
Antimicrobials that inhibit peptide cross-linking in peptidoglycan
Penicillin mode of action
Blocks peptidoglycan cross-linking in bacterial cell walls
Vancomycin
Antimicrobial that inhibits cell wall synthesis
Bacitracin
Antimicrobial that blocks steps in peptidoglycan synthesis
Why cell wall drugs have selective toxicity
Humans do not have peptidoglycan cell walls
Cell membrane disruptors
Drugs that damage microbial membranes
Polymyxin B
Antimicrobial that disrupts Gram-negative outer/cell membranes
Daptomycin
Antimicrobial that disrupts bacterial cell membrane function
Protein synthesis inhibitors
Drugs that target bacterial ribosomes
Why ribosomes are antimicrobial targets
Bacterial 70S ribosomes differ from eukaryotic 80S ribosomes
Aminoglycosides
Protein synthesis inhibitors that bind the 30S ribosomal subunit
Streptomycin mode of action
Binds 30S ribosome and causes codon-anticodon mismatching
Tetracyclines
Prevent tRNA from associating with the ribosome
30S ribosome inhibitors
Aminoglycosides and tetracyclines
Metabolic pathway inhibitors
Drugs that block essential microbial metabolic reactions
Sulfamethoxazole
Broad-spectrum drug that blocks the folic acid synthesis pathway
Folic acid pathway
Metabolic target blocked by sulfa drugs
Why sulfa drugs have selective toxicity
Bacteria synthesize folic acid differently than humans
Isoniazid
Narrow-spectrum drug used against Mycobacterium
Isoniazid mode of action
Interferes with mycolic acid synthesis
Mycolic acids
Waxy cell wall components found in Mycobacterium
Nucleic acid synthesis inhibitors
Drugs that block DNA or RNA synthesis
Fluoroquinolones
Drugs that inhibit bacterial DNA gyrase/topoisomerase
Ciprofloxacin
Fluoroquinolone that inhibits DNA synthesis
DNA gyrase
Enzyme needed for bacterial chromosome replication
Rifampin
Drug that inhibits bacterial RNA polymerase
Rifampin mode of action
Blocks bacterial transcription
DNA vs RNA synthesis inhibitors
Fluoroquinolones inhibit DNA gyrase, rifampin inhibits RNA polymerase
Antifungal drugs
Drugs used to treat fungal infections
Miconazole
Imidazole antifungal used for fungal skin infections and yeast infections
Imidazoles
Antifungals that affect fungal sterol metabolism
Antiprotozoan drugs
Drugs used to treat protozoan infections such as malaria
Mefloquine
Antiprotozoan drug used against malaria
Antihelminthic drugs
Drugs used to treat parasitic worm infections
Ivermectin
Antihelminthic used for roundworm diseases such as river blindness
Main antimicrobial targets
Cell wall, cell membrane, ribosomes, metabolic pathways, DNA synthesis, and RNA synthesis
Cell wall vs membrane target
Cell wall drugs block peptidoglycan, membrane drugs disrupt membrane integrity
Antibiotic resistance
Ability of bacteria to survive antibiotic treatment
Persister cells
Bacterial cells that survive antibiotic exposure without necessarily being genetically resistant
Superbug
Bacterium resistant to many different antibiotics
Resistance genes can spread by
Horizontal gene transfer, plasmids, conjugation, and transduction
Antibiotic selective pressure
Antibiotic exposure favors bacteria with resistance traits
Selection and resistance
Antibiotics select for resistant bacteria already present or acquired
Resistance mechanism: drug destruction
Bacterial enzymes destroy or inactivate the antibiotic
Resistance mechanism: reduced uptake
Bacteria prevent the drug from reaching its target
Resistance mechanism: target alteration
Bacteria change the drug target so the drug binds poorly
Resistance mechanism: efflux pump
Bacteria pump the antibiotic out of the cell
Efflux pump
Transport protein that ejects antimicrobial drugs from the cell
Misuse of antibiotics
Practices that increase selection for resistant bacteria
Antibiotic misuse examples
Not finishing prescriptions, using old antibiotics, treating viral diseases, and using antibiotics in animal feed
Antibiotics and viral disease
Antibiotics do not treat viral infections
Not finishing antibiotics
Can leave harder-to-kill bacteria behind and select for resistance
Outdated antibiotics
May be weakened and can contribute to resistance selection
Antibiotics in animal feed
Can select for resistant bacteria in agriculture
Why new antibiotics are hard to develop
Discovery and testing are expensive, profits may be low, and resistance can develop
Last-resort antibiotics
Drugs saved for infections resistant to many other treatments
High-yield resistance idea
Antibiotics do not create resistance on purpose, they select for resistant cells
Broad-spectrum vs superinfection
Broad-spectrum drugs can reduce normal microbiota, superinfection is secondary infection after that disruption