Antibacterial Agents: Introduction Flashcards
Define selective toxicity. Give examples
a
Define antibiotic spectrum (ie: narrow, extended, broad). Give examples
a
Define resistance (ie: natural, escape, acquired)
a
What are 4 biochemical differences between the pathogen target and the host which are then exploited by antibacterial agents?
1) Inhibiting metabolic pathways found in bacteria, not humans
2) Similar pathway in humans/bacteria, but have different enzyme structures
3) Macromolecular structure does not exist in human
4) Macromolecular structure differs between microbes and humans
What is an example of how inhibiting metabolic pathways found in bacteria, not humans, are exploited by antimicrobial agents
Folate metabolism:
Bacteria must create folate intracellularly —- mammalian cells get folate from environment
What is an example of how similar pathways in humans/bacteria, but have different enzyme structures are exploited by antimicrobial agents?
Protein synthesis:
- Bacterial ribosomes and mammalian ribosomes are different
Nucleic acid synthesis:
- DNA gyrase (bacteria) vs topoisomerase (humans)
- RNA polymerase structurally distinct in bacteria
What is an example of a macromolecular structure that does not exists in humans that is exploited by antimicrobial agents?
Cell wall synthesis:
- Peptidoglycan does not exist in eukaryotes!
What is an example of a macromolecular structure that different between microbes and humans that is exploited by antimicrobial agents?
Fungal cell membrane:
- Ergosterol —> major part of fungal membranes
- Whereas cholesterol —> in mammalian membranes
Describe natural (intrinsic) resistance
- Microbes lack a susceptible target for drug action
Eg:
- Fungal cell walls —> no peptidoglycan
- Mycoplasma —> no cell walls
- Pseudomonas —> drug cannot penetrate outer membrane
Describe the escape mode of resistance
Microbes are sensitive and antibiotics reach target BUT…
1) organism escapes b/c of precursor availability
2) Failure to lyse (no osmotic pressure difference)
3) Emphasizes important role for surgical drainage
What is acquired resistance? What are the two modes of acquired resistance?
Selective pressures produces successive generations of organisms w/ biochem traits that minimize drug action
1) Mutational (chromosomal) resistance
2) Plasmid mediated resistance
Describe mutational (chromosomal) resistance
- Multiple steps must occur for appreciable resistance
- Proper dosing and duration of antibiotic therapy can prevent this
Describe plasma mediated resistance
- Can emerge during a single course of treatment REALLY IMPORTANT
- Can code for resistance to multiple drugs (MDR gene)
Resistance occurs through:
1) Conjugation
2) Transduction
3) Transformation
What are the major mechanisms of bacterial resistance to antibiotics?
1) Altered targets
2) Enzymatic destruction
3) Alternative resistant metabolic pathway
4) Decreased entry
