2.2.1. Intro to Antibiotics Flashcards
Why are bacteria susceptible to sulfa drugs?
Unlike body cells, that can benefit from preformed folic acid in the environment, bacteria that make folic acid lack a system for its uptake and are susceptible to sulfonamides (inhibit the synthesis of folic acid, but not its utilization)
Antibiotics
An antimicrobial agent of microbial origin with a low molecular weight and a specific spectrum of activity (broad versus narrow)
Bactericidal agents
Are lethal (may or may not cause cell lysis) and, in general, are only effective against growing cells
Example: penicillin
Bacteriostatic agents
Reversibly inhibit bacterial growth and often resemble metabolite analogs (act as competitive inhibitors)
In what circumstances are bactericidal drugs preferred?
When the body’s defenses are insufficient to clear the invading agents
Reasons for Selective Toxicity
- Absence of the target from the host
- Permeability differences
- Structural differences in the target
Vancomysin
Targets peptidoglycan
B-lactam antibiotics
Best example is penicillin, which affects the biosynthesis of the murein layer of the bacterial cell wall
Reason for Gentamicin’s selective toxicity
Not affectively taken up by host cells
Reason for Chloramphenicol’s selective toxicity
Targets bacterial 50S ribosomal subunit but not host 60S
Selective Pressure
The process by which treatment with antibiotic selects for those bacteria that have acquired resistance. Exact reason that we do not over treat with antiobiotics
Sulfonamides
Broad spectrum bacteriostatic drugs that act as inhibitors of folic acid (starving the bacteria of bases necessary for DNA replication and transcription)
Trimethoprim
Prevents bacteria from using folic acid to form nucleotides
Methotrexate (MTX), trimethoprim (TMP), and pyrimethanmine
Inhibit dihydrofolate reductase in humans, bacteria, and protozoa (prevents utilization of folic acid). Exhibit selective toxicity (more toxic in protozoa and bacteria than humans).
Lead to decreased levels of dTMP, a mononucleotide
Para-Amino Salicylic Acid is effective against…
Effective against TB
Describe Rifampin and Rifabutin
- Bactericidal
- Narrow spectrum (strep, staph, neisseria, mycobacteria)
- Bind to beta subunit of RNA polymerase, inhibiting initiation of transcription
What is the common feature of drugs with the suffix -azole?
ergosterol synthesis inhibitor (e.g., Ketoconazole)
What is the common feature of drugs with the suffix -bendazole?
antiparasitic/antihelmintic [parasitic worms] (e.g., Mebendazole)
What is the common feature of drugs with the suffix -cillin?
peptidoglycan synthesis inhibitor (e.g., Ampicillin)
What is the common feature of drugs with the suffix -cycline ?
protein synthesis inhibitor (e.g., Tetracycline)
What is the common feature of drugs with the suffix -ivir?
neuraminidase inhibitor (e.g., Oseltamivir)
viral neuraminidase is responsible for the spread of the influenza virus
What is the common feature of drugs with the suffix -navir?
protease inhibitor (e.g., Ritonavir)
What is the common feature of drugs with the suffix -ovir?
DNA polymerase inhibitor (e.g., Acyclovir)
What is the common feature of drugs with the suffix -thromycin?
macrolide [ring structure] antibiotic (e.g., Azithromycin)
Describe Metronidazole
- disrupts DNA structure, inhibits DNA replication, and causes DNA breaks and secondary mutations
- pro-drug
- narrow spectrum against anaerobic infections
Resistance to metronidazole is caused by…
Mutations in the oxidoreductases that affect pro-drug conversion
Describe Quinolones
- Bactericidal Drugs
2. Act by inhibiting the action of bacterial topoisomerases, including DNA gyrase (G+) and topoisomerase IV (G-)
Nalidixic acid is used for…
used to treat UTI
Fluroquinolone is used for …
used to treat G+ and G-
Resistance to Quinolones is caused by…
- Mutations in the genes encoding the target enzymes DNA gyrase and topoisomerase IV (i.e., reduced binding)
- Efflux pumps
Describe the B-lactam antiobiotic pathway…
- Association w/ bacteria
- Penetration through outer membrane (G-)
- Interaction w/ PBPs
- Activation of an autolysin that degrades the cell wall
Resistance to B-lactam is caused by…
G+ produce extracellular B-lactamases that destroy the antibiotic before it comes into contact with the bacterial surface
Describe Daptomycin
A lipopeptide antibiotic that binds to the cell membrane of G+ and forms a disruptive ion channel that causes depolarization and rapid cell death
Oxazolidinones bind…
Bind the 50S subunit of bacterial ribosomes (entirely synthetic)
How do Polymyxins work?
Hydrophobic tail inserts into the cell membrane (head binds to PE and LPS) and disrupts the cell membranes of gram (-) bacteria
Resistance to Polymyxins is caused by…
G- bacteria have a structural modification of the lipid A moiety of LPS
Aminoglycosides work through…
Penetration of the outer membrane of G-, association with a two-stage active transport system, and binding to the 30S ribosomal subunit
Factors limiting successful chemotherapy
- Failure of the drug to enter the host cell (location)
- Abscess formation and necrosis
- Presence of foreign bodies
Types of resistance
- Intrinsic (e.g., mycoplasma does not have peptidoglycan so Vancomycin would not work)
- Acquired (horizontal gene transfer or spontaneous mutation)
- Selective pressure
Describe synergism between sulfa drugs and trimethoprim
Both drugs act on metabolism, but their sites of action are different (resistance to one does not mean resistance to both). Trimethoprim blocks the function rather than the synthesis of folic acid by inhibiting dihydrofolate reductase
Drug interactions
- Synergism (bactericidal + bactericidal)
- Antagonism (bactericidal + bacteriostatic)
- Indifference
Describe Tetracycline and Penicillin interaction
Antagonism: tetracycline blocks protein synthesis, preventing the cell growth required for penicillin to cause lysis
Plate Dilution Assay
Allows you to determine MIC (Minimal Inhibitory Concentration, lowest concentration of a drug that inhibits more than 99% of bacterial cells)
Can test several bacterial isolates at once
Tube Dilution Assay
Advantage: may plate the bacteria afterwards to see if the drug is bactericidal or bacteriostatic
Disadvantage: requires lots of tubes
Broth Microdilution Assay
Miniaturized version of the tube dilution assay
Advantage: may test a single bacterial isolate against a wide range of drugs to find multiple MIC’s
Disc Diffusion Method
Plate bacteria onto an agar plate, then place discs with antibiotic on them (CANNOT tell whether antibiotic is bacteriostatic or bactericidal)
