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Why is the bacterial cell wall a good target for antibiotic action?
It's different between animal cells and bacterial cells
its essential for bacterial life
How do gram + and gram - cells typically differ with respect to their cell envelope?
gram + does not have outer membrane and thick peptidoglycan
gram - has outer membrane and thin peptidoglycan
Why are gram - organisms typically more resistant to antibiotics?
the outer membrane acts as a barrier
Describe the structure of peptidoglycan. Which parts are relatively flexible and which are not?
Meshwork of glycan strands and and peptide cross-bridges
peptide cross-bridges are flexible and glycan strand are not
What is the function of the bacterial cell wall?
retain turgor pressure and give shape
How many molecules compose the cell wall surrounding an individual bacterium?
Why do bacterial cells have to have carefully coordinated enzymatic activities on the cell wall in order to grow?
because the turgor pressure and to let new molecules in you have to break bonds
For a rod shaped bacterial cell, cell wall growth can be divided into two distinct phases. What are they? Which of these is the only phase for a spherical cell?
Elongation and division
division is the only phase for a spherical cell
Describe a peptidoglycan precursor molecule in terms of the number and types of smaller molecular groups that it is made from.
Peptide chain (5)
Which part of a PG precursor is used to build glycan strand?
NAM & NAG
Which part of a PG precursor is used to build peptide cross-bridges?
What are the names of the enzymes that polymerized glycan strand and peptide cross-bridges, respectively?
tgase & tpase
What part of a PG precursor is used to link it to the existing PG wall structure?
Where are PG precursors located when they are used by enzymes to build new cell wall material? What is the whole precursor-carrier molecule called?
outface of cytoplasmic membrane
What is the name of the lipid carrier upon which PG precursors are built and transported?
which position on pentapeptides are typically linked together to form peptide cross-bridges in PG?
Why might rod shape be favorable to a bacterial cell?
surface area to volume ratio does not change
why type of fabric resembles the PG meshwork
what would happen if a bacterial cell had a shortage of precursor molecules?
it would not thrive or grow
How is the phosphorylation state of the bactoprenol carrier important for its role?
there is mono and di mono is needed to start
left with di after done which must be turned back into mono
Name two antibiotics that take advantage of the phosphorylation requirements of the bactoprenol cycle. How do they work?
bacitracin-binds the diphosphate and prevents dephospho rylation
friulimicin b-binds mono phosphate
what does a b-lactam ring look like? Why was it surprising to chemists?
square 4 member ring with nitro and oxygen
they thought it would unstable
what was the first b-lactam antibiotic discovered?
penicillin (isopenicillin n)
what are the 5 classes of b-lactamm antibiotics
penicillin, cephalosporins, carbapenems, monobactams, clavams
How are the clavam/penicillin sulfones different from the other 4 main classes?
not antibiotics they are a beta lactamase inhibitors
why is a clavam/penicillin sulfone plus another b-lactam class a good clinical combination?
the clavam protect the other antibiotic
why bacterial molecular structure is mimicked by the b-lactam ring?
d ala d ala
describe a second mechanism by which b-lactam antibiotics interfere with cell wall metabolism
new glycan strand can't be crossed in they get removed and the cells burn through PG precursors
if the b-lactam core structure is the real business end of the molecule, why have chemists made so many varieties with different R groups? at least 5 reasons
broader spectrum antibiotic, patent it, reduce allergens, make it more bio available, solubility, reduce susceptibility to b-lactamase
how are the mechanisms of action b-lactam antibiotics and glycopeptides like vancomycin similar, and how are the different?
similar-they both inhibit transpeptidation
diff- b-lactam binds to enzyme and vancomycin binds to substrate
Vancomycin is only active against gram + whereas many b-lactam antibiotics are active against both gram+ and gram - bacteria, why?
vancomycin is big so it cannot pass through the outer membrane
second generation glycopeptide antibiotics like teicoplanin, dalbavancin and oritavancin contain hydrophobic lipid tails in addition to their d-ala-d-ala binding domains. how might these lipid tails aid in antibiotic activity?
insert into cell membrane to increase concentration and then poke holes in membrane
what step of PG synthesis is targeted by fosfomycin?
What step of PG synthesis is targeted by tunicamycin? why is this compound not used clinically?
MraY its toxic
Antibiotics tech as Oisin are primarily used for food preservation. What is their mechanism of action?
binds diphosphate to lipid II and then poke holes in membrane
what is the target moenomycin? why is this antibiotic not used clinically?
not bioavailable in blood
what product typically contains bacitracin
phospholipid membranes are common to both bacterial and eukaryotic cells. how do we know that eukaryotic and bacterial cell membranes can be distinguished on the molecular level?
antimicrobial peptides and they harm bacterial cell and not ours
what is the likely basis of AMPs being able to specifically target bacterial membranes>
bacteria has more negative charges in their phospholipids
why is colistin (polymyxin E) only used as a last resort antibiotic?
how do polymyxins specifically target gram - bacteria?
they are + charged so they are attracted to the LPS - charge
why is daptomycin (Cubicin) only available clinically as an injectable antibiotic?
it is too large
what is the clinical use of daptomycin (what bacterial organisms is it used to target?)
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