micro poop 3. Flashcards
What are the newest antibiotics targeting?
plasma membrane - bacteria have a step in plasma membrane making that we don’t
Why is there so much antibiotic resistance?
use on farm animals before they’re even exposed
natural (intrinsic) resistance
chromosomally mediated and is predictable
mutational resistance
random mutation - secondary resistance occurring after therapy with the antimicrobial has begun
transferable resistance
plasmid-mediated through conjugation (mating), transaction (bacteriophge transmission), transformation (uptake of DNA from environment)
What are the two transposable genetic elements?
transposons and insertion sequences —> “jumping genes”
What is the essential element to the transposition process?
that both elements are flanked on either end by short identical sequences of DNA in reverse order (inverted repeats)
What is required for transposons and insertion sequences to work?
existence on a replicon (chromosome, bacteriophage, plasmid) because they are incapable of autonomous self-replication
insertion sequences
mobile genetic elements that are known to encode only functions involved in insertion events (ability to turn on/off because they don’t want to waste energy on things they don’t need)
What does Staphylococci have to give it resistance?
insertion sequence
transposon
central sequence containing the phenotypic marker gene and transposase genes (have other gene material outside of what an insertional sequence has)
integron
DNA elements with the ability to capture genes by site-specific recombination - provides a convenient insertion site for antibiotic-resistance genes from foreign DNA sources
What is the difference between an integral and a transposon?
transposon is mobile, integrons (nonmotile) can be within transposon
gene cassettes
discrete genetic elements that may exist as free, circular, non-replicating DNA molecules when moving from one genetic site to another - include a gene and an integrase-specific recombinationn site
How can cassettes be added/deleted/moved?
due to the attC site
What are the 7 mechanisms of antibiotic resistance?
enzymatic inactivation, decreased permeability, efflux (kick antibiotic out), alteration of target site, protection of target site, overproduction of target, bypass of inhibited process
How do organisms resist b-lactam antibiotics?
with beta-lactamases (bacterial enzyme) that inactivate beta-lactam antibiotics by hydrolysis of the beta-lactamase bond
How does beta lactamase work?
require a serine or zinc atom moiety at the active site to hydrolyze the beta-lactam ring
How are beta lactams being modified to avoid resistance?
created beta-lactamase inhibitors and inhibitor combinations (bind irreversibly to beta-lactamases)
What is special about the extended spectrum cephalosporins and carbapenams?
they are resistant to beta-lactamases
What drug is most effective against ESBL-producing enterobacteriaceae?
carbapenems (any drug that ends in penem)
What common organisms primarily have extended-spectrum beta-lactamases?
klebsiella, e coli, proteus
What are AmpC Beta-lactamases?
differ from ESBLs because they are resistant to available beta-lactamase inhibitors and can hydrolyze the cephamycins - usually produced at low levels by organisms - resistance when produced at high levels (only carbapenems and 4th generation cephalosporins still effective)
What are super bugs?
carbapenem-hydrolyzing enzymes - most diverse group of all beta-lactamases - resistant to inhibition by beta-lactam inhibitors (plasmid encoded)
NDM-1 producing enterobacteriaceae
no antibiotics that touch it - carbapenase
How does staphylococci resist beta-lactams?
production of beta-lactamases and production of modified transpeptidase targets that are impervious to antibiotic activity (such as MRSA)
What type of microorganism is now resistant to penicillin? What has been our response?
pneumococci and enterococcus - we no longer use antibiotics for simple things like ear infection unless it is a repeated one
IS431
integron that can trap and cluster resistant genes for other antibiotics (found on the MecA gene plasmid - how MRSA is resistant)
How is S. Aureus methicillin resistant?
expression of the mecA gene which encodes PBP2a - protein with low affinity for beta lactam antibiotics
PBPs
transpepdidases in the cytoplasmic membrane - catalyze the synthesis of the peptidoglycan that forms the cell wall - alterations to this can lead to beta-lactam antibiotic resistance (such as PBP2A on the mega gene)
How does vancomycin work?
blocks cell wall synthesis by binding to the C-terminal D-Ala-D-Ala residue
How are strains becoming resistant to vancomycin?
adaptive multifactorial response to sublethal vancomycin exposure - thicker cell walls trap vancomycin, blocking action
How does acquired resistance to ahminoglycosides happen?
combination of decreased drug uptake, efflux pump activity, enzymatic modification of the drug
How does resistance to tetracycline happen?
efflux pump and ribosomal protection (sometimes both)
How does resistance to macrolides happen?
alteration of target site (ribosome) and efflux
How does resistance to sulfonamides happen?
mutational (alteration of metabolic pathway or target site)
How does resistance to trimethoprim happen?
changes in cell permeability and altered metabolic pathway
How does resistance to fluoroquinolone happen?
alteration of target enzymes (esp DNA gyros and topoisomerase)
