Antibiotic Resistance Mechanisms Flashcards
6 targets of antibiotics
- cell wall synthesis
- DNa replication
- RNA synthesis
- proteins synthesis
- folic acid synthesis
- membrane disruption
example and mechanism behidn disrupting the cell wall
- beta lactams (penicillin)
- during cell wall growth, an enzyme called transeptidase facilitates the linking of two peptide side chains off of M of the peptidoglycan cell wall
- it does this by removing one D-Ala and linking the next one in the chain to an adjacent L-Lys
- beta lactam’s backbone mimics that of D-Ala, D-ALa but the transpeptidase enzyme does not recognize it
blocking DNA replication
- fluoroquinilones
- block DNA gyrase and topoisomerase
- this disrupts DNa synthesis
blocking RNa synthesis
-rifampicin
-
blocking protein synthesis
- tetracylcines, macrolides
- tetracyline block the binding of amino acyl tRNA
- macrolides block the extension of the nascent polypeptide by blocking the A site
folic acid synthesis (blocking the synthesis of DNA subunits)
-sulfonamides
membrane disruption
- daptomycin for gam +
- colistin for gram -
- daptomycin forms a pore in the membrane
- colistin binds to LPS and disrupts the membrane
urgetn threats
- C diff
- neisseria gonorrhea
- carbapenam resistant enterobacteriaceae
how do bacteria resist the action of antibiotics?
-5 methods
- inactivating the antibiotic
- modifying or replacing the target
- remove the antibiotic from the cell via eflux pumps
- prevent uptake of the antibiotic
- develop persister populations: cells neither grow nor die during antibiotic exposure
inactivating the antibiotic
- beta lactam is an ex
- a protease cleaves the beta lactam ring
- secreted from the cytoplasm
- the gene for protease is often encoded on a plasmid DNA
modifying or replacing the target
- vancomycin resistance
- vancomycin blocks cell wall sythesis by binding the D ala D ala and blocks transpeptidase
- the bacterial cell with resistance will replace the first D ala with a D lactate, inhibiting the vancomycin from binding
removing the anitbiotic from the cell
- done via eflux pumps
- this causes multi drug resistnace
- AcrAB efflux pump uses a proton gradient to pump out the antibiotics, energy dependent
preventing antibiotic uptake
- decrease outer mem porin gene production in gram neg (regulation of OprD in p. aeruginosa)
- increased thickness/synth of the peptidoglycan cell wall gram pos
- capsule formation
- biofilm production
OprD
- gene that forms a pore in the gram neg membranes allowing for small nutrients including amino acids
- major route for carbapenem influx into the periplasm
- in drug resistant strains there is a negative regulator of the RNA polymerase for this gene
develop persister populations
- cells neither grow nor die during antibiotic exposure
- this happens when the full course of antibiotics is not taken
intrinsic resistance
-the organism is innately resistant to the antibiotic an example is gram negative resistance to vancomycin
acquired resistance
-the organism develops the abilitu to resist the antibiotice through acquiring mutations ot new genes via horizontal gene transfer
acquiring resistance through a mutation
- alter gene expression
- alter protein structure and or function
rifampicin resistane in TB
- rifampicin targets the beta sbunit of the bacterial RNa pol, rpoB
- mutations in the rpoB confer reisstance to rufampicin
horizontal gene transfer
- the transfer of genetic aterial between different organisms
- transformation (plasmid)
- conjufation (pili)
- transduction (phage)
what promotes antibiotic resistance?
- overuse/misprescribing (clinician)
- non-adherence to antibiotics regimens (patient)
- widespread use in agriculture
how to combat ABR
- increasing awareness and monitorin for ABR organisms within clinial and agricultural settings
- reduce.eliminate unnecessary prescription
- makinf sure patients understand the seriousness of ABR and the need for strict dherence to drug regiemns
- develop new druga
- modification of antibiotics use in ag
- using more thorough diagnosit methods
