Flashcards in 1-30 Mechanisms of Resistance to Antibiotics Deck (23):
innate to resist activity of an abx due to inherent structural or functional characteristics
Ex) M.Tuberculosis, Pseudomonas aeruginosa
resistance may occur due to chromosomal mutation that is spontaneous or random
Mutability depends on structure and number of genes in which mutations can produce selectable phenotype
Acquired resistance - occurs when microorganism obtains ability to resist activity of abx to which it was previously susceptible.
Acquisition of gene(s) conferring resistance through horizontal gene transfer (process of swapping genetic material between neighboring bacteria)
Cite the differences among transformation, transduction, and conjugation with respect to how bacteria acquire extrachromosomal DNA
a. Tranformation - involves uptake of shore fragments of naked DNA
Transduction - involves transfer of DNA from one bacteria into another via bacteriophages
Conjugation - involves transfer of plasmids via sexual pilus, requires cell-cell contact
Major Mechanisms by which bactera can be resistant to antibiotics(7)
1. enzymatic inactivation (beta lactamase)
2. Efflux (push out)
3. Alteration of Target Site (MRSA PBP2->PBP2a)
4. protection of target site
5. overproduction of target
6. bypass of inhibited process
7. decreased permeability
4 classes of beta lactamases
narrow spectrum beta lactamases, extended spectrum beta lactamases (ESBLs), Amp C Beta lactamases, carbepenemases
describe beta lactamase
enzyme inactivates ring by splitting the amide bond
most common producers?
extended Spectrum Beta Lactamases - enzymes that mediate resistance against 3rd and 4th generation cephalosporins
Klebsiella, E.coli, and Proteus.
May treat with carbepenem
Amp C beta lactamases
chromosomal enzymes that confer resistance to penicillins, narrow spectrum cephalosporins.
i. Not susceptible to beta lactamase inhibitors
ii. Members of enterobacteriaceae except Klebsiella and E.coli
iii. Has been introduced into plasmids
largest resistance, hydrolyze carbepenems but also broad spectrum penicillins
i. Klebsiella pneumonia carbapenemases (KPC) and resistant enterobacteriaceae (CRE)
Discuss the action of beta lactamase inhibitors.
They have a beta lactam ring which beta lactamases preferentially bind to. Not antimicrobic
how are antibiotic genes typically transferred?
mainly through conjugation
what are transposons?
jumping genes, can jump from one place on chromosome to another, from one plasce on plasmid to antoher, or chromosome to plasmid.
Some organsisms are hard wired - but what is this gene picks up the excision and incision sequences? Turns into a transposon. What was once a "hard wired" gene, can now be found on plasmid
have own promoters. Are mobile genetic elements that are known to encode only fuctions involved in insertion events.
May contain partial or complete, alllow activation of downstream genes
Integrons - gene capturing machine. Little sequences with promoter sequences with a binding site (atttl1). The chomosomal casette comes insid ecell, gets into integron, unfolds, binds. Can also have many in a row.
Impact of integron-borne promoter region
The expression of cassette-associated resistance genes is influenced by their position in an integron and proximity to the promoter sequence and the number of cassettes in the integron.
as bacteria are exposed to antibiotics..
can take genes from promoter to now upregulate resistnace genes. (rpeviously sensitive, now resistance).
why would you ever want resistance genes downregulated?
Being resistant is energy internsive. If you don’t need to be promoting a beta lactamase, turn it off. Being attacked? Turn it back on (upregulate)
how to treat staph aureus?
it produces beta lactamase
give script for both inhibitor and antibiotic, such as augmentin
procedure if a patient has CRE's?
contact plus - strict isolation
Carbepenam-hyrolyzing beta lactamases (produced by CRE's - carbepenem resistant enterobacetre) - most diverse of all beta lactamases
-recognize and hydrolyze all beta lactamaes
-started of as kleb chromosome, turned into a trasnposon
how to treat MRSA