Antimicrobials and Drug Efflux Flashcards
outline the cell wall structure of gram-negative bacteria
thin layer of peptidoglycan in periplasmic space between inner and outer membranes
outline the structure of gram positive bacteria
only have a single lipid membrane surrounded by a cell wall composed of a thick layer of peptidoglycan and lipoteichoic acid, anchored to the cell membrane via diacylglycerol
outline the cell wall of mycobacteria
thin layer of peptidoglycan and arabinogalactin and a thick layer of mycolic acids - this cell wall surrounds a single lipid membrane
what are the ways in which bacteria become drug resistant
decreased influx
efflux pumps
drug inactivation
resistance mutations
membrane/cell wall
function of transpeptidases
responsible for cross-linking peptidoglycan strands in bacterial cell walls
how does penicillin/beta-lactams perform their function
binds and inhibits transpeptidase
leads to weakened cells that cannot resist osmotic pressure
how are beta-lactams able to bind to transpeptidase
the beta-lactam ring is structurally similar to the D-Ala-D-Ala portion of peptidoglycan precursor
when are beta-lactams most effective
against dividing bacteria which need transpeptidase to synthesise new cell walls
what type of bacteria can beta-lactams target
gram+
and some gram-
how does the use of penicillin lead to antibacterial resistance
bacteria develop beta-lactamase that degrade the beta-lactam ring
inhibiting its transpeptidase binding capabilities
what is ciprofloxacin
a flouroquinolone
what does ciprofloxacin bind to
DNA gyrase
topoisomerase IV
function of DNA gyrase and how does ciprofloxacin affect it
cleaves DNA backbone
ligases the DNA - ATP dependent
done by introducing negative supercoils
ciprofloxacin - prevents it from re-ligating
how can bacteria become resistant to ciprofloxacin
mutations in the gyrAB and parCE genes to reduce affinity to DNA gyrase and topoisomerase IV
overexpression of efflux pumps to reduce ciprofloxacin M
how does ciprofloxacin inhibit topoisomerase IV
it intercalates into DNA at the nicks introduced by topoisomerases
what is erythromycin
a macrolide
ribosome 50s subunit inhibitor - protein synthesis inhibitor
how do macrolides inhibit protein synthesis
bind to the exit tunnel of 50s ribosome subunits
how do bacteria gain resistance against macrolides
methylation of ribosomes to reduce macrolide affinity
function of tetracycline
prevents protein synthesis by binding to the 30s subunit
inhibits the tRNA’s binding to the acceptor side of the mRNA
how do bacteria develop resistance to tetracycline
efflux pumps
changing the 30s ribosome subunit binding sites
what is polymyxin B
a group of peptides effective against gram- bacteria
what is the mechanism of action of polymyxin B
they act as cationic detergents that bind to negatively charged LPS on the outer membrane
results in disruption of the outer membrane
outer membrane disruption allows polymyxin to disrupt inner membrane
increases cell permeability
leads to cell death
why have polymyxin’s been historically restricted to topical use (like creams n stuff)
they are very toxic when given systemically
how do gram- bacteria in particular develop resistance to polymyxin B
they modify their LPS by substituting anionic groups with cationic
formation of capsules to protect their membrane
over-expression of OprH - a protein that increases outer membrane stability by binding to LPS
