lec 8-9 antibiotics Flashcards
bacteriostatic
stops bacteria from reproducing without killing them
inhibits protein synthesis
e.g. macrolides
bacteriocidal
kills bacteria
e.g. fluorouquinolones
bacteriolytic
destruction of bacteria by damaging their DNA or cell wall
broad spectrum antibiotics
act against a wide range of disease-causing bacteria including gram +ve and -ve
types of antibiotic
macrolides
fluoroquinolones
cephalosporins
macrolide structure
12-16 macrolactone rings with amino sugars attached
macrolide binding site
large 50S ribosomal subunit
macrolide functions
inhibit protein synthesis
if protein cannot exit via tunnel in ribosome, then translation is inhibited
leads to cellular growth and arrest
why are gram +ve bacteria difficult to target
thick peptidoglycan layer
fluoroquinolone structure
bicyclic core structure
bacteriocidal
fluoroquinolone function
targets DNA gyrase and Topoiosomerase IV
commonly used for urinary infections
causes irreversible damage
entry of fluoroquinolones into gram +/-ve bacteria
passive diffusion into gram +ve bacteria and via outer membrane porins in gram -ve
examples of fluoroquinolones
ciproflaxin
oxoflaxin
cephalosporins
broad spectrum
semi-synthetic beta-lactam antibiotic
derived from mould cephalosporium
chemically related to penicillins
function of cephalosporins
interfere with bacterial cell wall synthesis
clostridium difficile
pathogen that disrupts GI tract
dysbiosis
disruption of gut microbiota
bacteriophages as antimicrobials
use of phages (virus) to treat pathogenic bacterial infections
advantages of using bacteriophages as antimicrobials
specific
cheap
disadvantages of using bacteriophages as antimicrobials
narrow spectrum
bacterial resistance
stages of infection of bacteriophage into bacteria
- adsorption to specific receptor
- DNA injection
- peptidoglycan degradation - DNA transferred to cell
- redirection of host metabolism to phage DNA replication and phage protein sythesis
- assembly of phage particles
- bacterial cell lysis and phage progeny release
which bacteriophage late proteins are responsible for host cell lysis
lysins
holins
murein synthesis inhibitors
anti-virulence stratgies
inhibiti specific mechanisms
targeting toxins
inhibiting seccretion systems
UPEC mechanism
binds and invades cell
replicates inside cell and forms biofilm
biomass disperses and exits cell
spreads to new cells
synergistic effect
when interaction causes an increase in the effects of one or both of the drugs
synergistic drugs
suppress drug-susceptible populations more the single-drug therapies
antimicrobial resistance
resistance of a microorganism to an antimicrobial drug that was originally effective for treatment of infections caused by it
2 methods to measure resistance
increase in minimum inhibitory concentration (MIC)
minimal bacterial concentration (MBC)
minimum inhibitory concentration (MIC)
lowest concentration of antimicrobial that will inhibit visible growth of microorganism overnight
limitation of MIC
micro bacteria takes 4 weeks to grow, too slow to change overnight
minimum bactericidal concentration (MBC)
lowest concentration of an antimicrobial that will kill bacteria in vitro
how do we know how much antibiotic to administer
break points
break points
chosen concentration defining whether bacteria is susceptible or resistant to antibiotic
if minimum inhibitory concentration (MIC) is more than the susceptibility break point…
.. then bacteria is intermediate or resistant to antibiotic
if MIC is less than or equal to the susceptibility break point …
..then bacteria is susceptible to the antibiotic
bacteriostatic agent
stops bacteria from reproducing
reaches MIC levels in blood/tissues
bactericidal agent
kills bacteria
reaches cidal levels in blood/tissues
broad spectrum agent
low MICs for many different bacteria types
- very weak concentration of antimicrobial would kill many bacteria
narrow spectrum agent
low MICs for just a few bacterial types
susceptible (sensitive) microbe
inhibited by an agent at a low MIC
resistance microbe
only inhibited by agents at a high MIC (takes higher dose to kill them)
molecular mechanisms of resistance
- degradation of drugs by enzymes
- modification of drugs by enzymes
- alteration of drug target site
- drug efflux pumps
beta-lactamase mechanism
degradation
break down beta lactam ring
e.g. cephalosporins - interfere in cell wall synthesis - bactericidal
common antibiotic resistance
MRSA
methicillin
in MRSA
is a beta-lactam antibiotic so broken down by beta-lactamases
penicillin binding protein (PBP)
penicillin binding proteins join peptide bridges in peptidoglycan layer and facilitate cell wall synthesis
inhibited by beta-lactam antibiotics
what prevents penicillin from binding to a protein
pencillin binding proteins bind to beta-lactam antibiotics, preventing cell wall synthesis
therefore lactam ring is broken down
streptomycin
aminoglycoside
protein synthesis inhibitor
targets ribosome 30S subunit
modifies drug by phosphorylation
prevents drug from binding
modifying membrane permeability of transport systems…
prevents entrance of drug into a cell
drug efflux pumps
important for mediating resistance to many antibiotics
protein secretion system
rids of toxic products from inside cytoplasm to outside outer membrane
RND family transporters
used by drug efflux pumps
powered by electrochemical gradient
transposons
transposable elements
can change their position within a genome
can create or reverse mutations and alter a cell’s genetic identity
mediators of resistance
vertical gene transfer
- spontaneous mutant resistant strain
- apply antibiotic and only
individual resistant strain will survive and reproduce - all susceptible bacteria will die
- you have to wait for selection pressure (antibiotic) to occur
horizontal gene transfer
- transfer of genetic material between mature cells
- no increase in number of cells but increase in number of resistance cells
- transformation, conjugation and transduction
spread of antibiotic resistance genes
horizontal and vertical gene transfer
transformation
manipulation of a bacteria enabling it to take up DNA
protein secretion system (type 6) used to kill surrounding cells and uptake their DNA
natural transformation mediated by competence proteins
conjugation
resistance gene moves with replicating plasmid into a new cell (no replication involved)
transduction
resistance gene hijacks and integrates host cell plasmid with bacteriophage DNA
R plasmids
important in resistance
have genes for conjugation fertility factor
conjugation plasmid
a plasmid that is transferred from one bacterial cell to another during conjugation.
conjugation fertility factor
allows genes to be transferred from a bacterium carrying the factor to a bacterium lacking the factor by conjugation
origin of transfer
short sequence of genes necessary for DNA transfer from bacterial hst to recipient during bacterial conjugation
cis acting - oriT is found on same DNA that is transferred
