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093014 - Bacterial Resistance to Antibiotics
N/A
40
Immunology
Graduate
10/05/2014

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Term
ESKAPE - 6 families of bacteria that are developing resistance
Definition
Escheria, Staph, Klebsiella, Acinetobacter, Pseudomonas, Enterobacter
Term
Ways that bacteria can exchange genes (3)
Definition
Transformation, Transduction, Conjugation
Term
Antibiotic resistance mechanisms of bacteria (5)
Definition
Block entry, block binding, replace target, destroy antibiotic, don't activate antibiotic
Term
Resistance - formal definition
Definition
Bacteria are not inhibited by clinically-achievable, "nontoxic" levels of the antibiotic
Term
Transformation - general process
Definition
Uptake of foreign bacterial DNA by a new bacteria. 1) Cell lyses, releasing DNA; 2) DNA is taken into new cell; 3) DNA is integrated & expressed
Term
Transduction - bacteriophage example
Definition
Acquisition of new DNA via a vector. Normally viruses replicate & take their own DNA, lyse cell, and leave; bacteriophages can take some BACTERIAL DNA when they leave, thus accomplishing GENE TRANSFER if they infect a different bacterial strain (and, this doesn't kill the new bacteria either)
Term
Conjugation - general process
Definition
Direct cell-cell transfer, via sex pili
Term
Conjugative plasmid; definition
Definition
Plasmids that encode for the ability to transfer from cell to cell. Normal plasmids have an origin site "ori"; conjugative plasmids have a 2nd origin site "oriT" for DNA Transfer Apparatus
Term
Replicon - definition
Definition
Able to replicate as independent DNA molecules from their own origins. Applies to both plasmids and chromosomes
Term
Imported resistance (transformation, transduction, conjugation) vs Mutational resistance?
Definition
Prob of mutational = 1/10^6; prob of imported = 1/(10^3-10^5), a 10-1000x increase
Term
Intrinsic resistance
Definition
Inherent property of an organism making it antibiotic-resistant. Fungi produce their own penicillin, but they don't make peptidoglycan anyway so they are intrinsically B-lactam resistant. Not clinically relevant, because bacteria can't pick up this mutation from fungi
Term
Acquired (active) resistance
Definition
Obtains the ability to resist something it previously was unable to. S. fradiae makes neomycin AND an enzyme that inactivates neomycin that enters. Clinically relevant, because these active abilities can also be acquired
Term
Example of how E. coli has acquired neomycin resistance
Definition
Similar aminoglycoside phosphotransferase sequence to S. fradiae, which is neomycin resistant - probably acquired the resistance from S. fradiae. Very unlikely that this is random
Term
ID the mechanism and type of example: Altered porin doesn't let B-lactam in
Definition
Blocking entry - mutational example
Term
ID the mechanism and type of example: Protein in membrane which actively pumps out tetracycline
Definition
Blocking entry - Imported example
Term
ID the mechanism and type of example: 1) Gram negative outer membranes/porins don't let vancomycin in. 2) Aminoglycoside uptake requires aerobic metabolism
Definition
Blocking entry - Intrinsic example
Term
ID the mech and type: RpsL (ribosomal binding ptn) doesn't bind streptomycin
Definition
Altering target - mutation
Term
ID the mech and type: RNA pol subunit doesn't bind rifampicin
Definition
Altering target - mutation
Term
ID the mech and type: RNA CH3transferase methylates rRNA, so erythromycin can't bind
Definition
Altering target - imported
Term
ID the mech and type: pNAM-NAG which doesn't bind vancomycin
Definition
Altering target - imported
Term
ID the mech and type: Alternative enzyme resistant to sulfonamides
Definition
Replace target - imported
Term
ID the mech and type: Alternate DHFR resists trimethoprim
Definition
Replace target - imported
Term
ID the mech and type: B-lactamases, aminoglycoside-inactivating enzymes
Definition
Hydrolyzing/modifying antibiotic - imported
Term
ID the mech and type: KatG that doesn't activate Isoniazid prodrug
Definition
Failure to activate antibiotic - mutation?
Term
Multigene resistance mechanism (vancomycin)
Definition
Incorporates lactate into Vancomycin so it can't bind, and gets rid of non-resistant forms. Requires many genes (VanA, VanH, VanX, VanY)
Term
Biggest barrier to interspecies gene transfer
Definition
The need for homologous recombination
Term
RecA function
Definition
Brings together 2 pieces of DNA for homologous recomb
Term
How many BP must match for RecA to work
Definition
~100 BP. This is a tough barrier to overcome; low probability of a foreign gene matching 100bp randomly
Term
What process circumvents the barrier of sequence homology and RecA function
Definition
Transposition - two types; cut and paste, and replicative
Term
Three basic types of DNA Transposons (and one mixed category type)
Definition
Insertion sequences, composite transposon, non-composite/simple transposons, (and, conjugative transposons)
Term
Insertion sequence structure
Definition
Transposase gene (1000 BP) with Inverted Terminal Repeats (10-30bp, transposase cutting sites) on each end
Term
Composite transposon
Definition
Two transposons with a gene (≤10K BP) in the middle; outermost ITRs can be cut and moved as a full thing. Each insertion sequence of a composite transposon is called a"Long Terminal Repeat" LTR
Term
Noncomposite/simple transposon
Definition
Long gene (>1000 BP) in between two ITRs. Like a giant insertion sequence
Term
Can transposition ("jumping genes") happen in other things besides bacteria?
Definition
Yes, it can happen in humans - RAGs in Ab/TCR gene assembly
Term
Conjugative transposons
Definition
Hybrid of transposon and conjugative plasmid; transposon leaves plasmid, conjugates, re-integrates with new cell's plasmid. This optimizes efficiency of horizontal gene transfer
Term
Surrogate selection
Definition
Transposons within transposons; selection of any one resistance gene will select for an entire plasmid containing multidrug resistance
Term
Major resistance reservoirs
Definition
Farms (antibiotic feed to fatten livestock, crop dusting) & hospitals (prophylaxis, defensive medicine)
Term
Drug-resistant salmonella
Definition
Subtherapeutic tetracycline to cows --> selected for Salmonella that was resistant to tetracycline AND ampicillin (MDR). People that ate the product and also had ampicillin for strep throat treatment would awaken the dormant salmonella
Term
Triclosan - define, and mechanism of what it would make resistant
Definition
Antibacterial soap. Similar target as Isoniazid for TB therapy, so it may be developing a drug-resistant TB strain
Term
Procalcitonin
Definition
Can be used as biomarker for infection to avoid unnecessary AB use
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