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24 Cards in this Set
- Front
- Back
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What are the two main origins of drug-resistant strains
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Chromosomal Mutation
Genetic exchange or chromosome, plasmid or transposons |
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Chromosomal Mutation Rate
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1 in 10^6 cell divisions
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Through what mechanisms can resistance be transferred/
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Transformation
Conjugation Transduction |
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R-plasmids
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Resistance plasmids
Those involved in transference of drug resistance Contains resistance transfer factor (RTF) to start process of conjugation and "r" determinant that contains the actual link genes that confer resistance |
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Conjugative plasmid
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Self-transmissible
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Resistance transfer factor
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AKA RTF
Component of R-plasmid that initiates and controls conjugation |
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"r" determinant
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Actual segment of genome in R-plasmids that contain one or more linked genes that confer resistance
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Non-conjugative R-plasmid
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Unable to initiate self-transfer and does not encode for a sex pilus
Rarely encodes for more than 2 antibiotic resistance genes Transfer is mediated by mobilization |
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Mobilization
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Conjugative plasmids cause transfer of nonconjugative plasmids
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Transposons
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DNA sequences with capacity for excising themselves from one genome and inserting into another
Resistance gene can transpose from plasmid-plasmid, plasmid-chromosome, plasmid-bacteriphage They have a predilection for plasmids |
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What are the physiological or biochemical mechanisms of drug resistance
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Decreased permeability of organism to drugs
Inactivation of inhibitor by enzymes produced by resistance organism Modification of properties of drug receptor site Increased synthesis of an essential metabolite that is antagonistic for drug |
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Which antibiotics have organisms developed a decreased permeability to?
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Tetracycline
Sulfonamide Beta-lactams |
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Intrinsic Permeability
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Relative difficulty of certain antibiotics to get into the cell
Has to do with the size of the antibiotic like Vancomycin and Bacitracin |
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Differential Permeability
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Relative resistance based on the differences in F porin sizes in which the antibiotics traverse
H flu < E.coli < Pseudomonas aeruginosa |
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Efflux
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Antibiotics get pumped back out using either ATP hydrolysis driven pumps or proton-motor force driven pumps
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What are ways to decrease permeability of organisms to drugs
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Intrinsic Permeability
Differential Permeability Efflux |
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Which antibiotics have organisms inactivated by enzymes to develop resistance?
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Beta-lactam (through Beta-lactamases)
Aminoglycoside (through acetyltransferase, phosphotransferase, and adenyltransferase) Chloramphenicol (through transacetylase These resistance forms are mostly carried on plasmids |
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Beta lactamases
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Enzyme of resistance in organisms that decrease effectiveness of Beta-lactam antibiotics through hydrolysis
Classified into serine enzymes (Class A,C,D) and metalloenzymes that use Zinc (Class B) Functions outside the cell in Gram+ and inside the periplasmic space in Gram- |
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Inducible beta-lactamase
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Gene responsible for production of beta lactamase is repressed until beta-lactam antibiotic is introduced
Antibiotic de-represses the gene |
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What are the ways organisms have developed to modify the drug receptor side rendering them resistant to antibiotics
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They alter the 50S ribosomal subunit (resistant to erythromycin)
They alter PBP (resistant to penicillin and methicillin) |
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What antibiotics has resistance occurred through modification of drug receptor site
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Erythromycin (through altering 50S ribosomal subunit)
Penicillin/Methicillin (through altering PBP) |
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How are antibiotics rendered ineffective through synthesis of resistant pathways
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Either mutational or plasmid mediated
Production of altered dihydropteroate synthetase (1000x less sensitive to sulfonamide) Production of altered reductase (1000x less sensitive to Trimethoprim) |
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What drugs have developed resistance due to synthesis of a resistant pathway?
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Sulfonamide (through the plasma mediated production of altered dihydropteroate synthetase)
Trimethoprim (through plasma mediated production of altered reductase in folic acid pathway) |
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What are drivers of antibiotic resistance
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Unnecessary use of antibiotics
Use of antibiotics in agricultural industry Individuals taking old prescriptions |
