Mechanisms of Drug Resistance Flashcards
———- drugs may have mutagenic properties and non-specifically increase the probabilities of many kinds of mutation.
Bacteriostatic
Transformation
Small pieces of DNA containing genes for drug resistance are taken up from the environment and incorporated into the genome of a drug-sensitive bacterium.
Transduction
Resistance genes are transferred from one bacterium to another by a bacteriophage.
Conjugation
Drug resistance genes contained in a plasmid are transferred from one cell to another through a direct connection formed by a pilus.
Transposition
Allows resistance genes to move between plasmid and chromosomal DNA. Requires some enzymatic help.
Biochemical mechanisms of Drug resistance (7)
1) Decreased intracellular Drug level
2) Increased Inactivation of the drug
3) Decreased conversion of a drug to a more active compound.
4) Increased concentration of a metabolite that antagonizes drug action.
5) Altered amount of Target enzyme or receptor
6) Decreased affinity of the receptor for the drug
7) Decreased activity of an enzyme required to express the drug effect
What are the mechanisms of decreasing intracellular drug level?
Decreased drug entry (mutations in porin proteins)
Increased drug efflux (acquisition of genes that encode an active efflux system for the drug)
What is mechanism of increasing inactivation of the drug?
Bacteria can produce enzymes that render antibiotics biologically inert.
Augmentin
B-lactamases inhibitor with amoxicillin
B-lactamases
Enzymes that cleave penicillins and cephalosporins
In the absence of autolytic enzymes, drugs that inhibit cell wall synthesis are —– rather than ——
bacteriostatic
bactericidal
Autolytic enzymes
breakdown sections of the proteoglycan matrix during growth
