Antibiotics: Cell wall biosynthesis and its inhibitors Flashcards
T/F: Enzymes of cells biosynthesis are unique to bacteria and are good targets for antibiotics
True
T/F: Gram negative have a thick peptidoglycan wall
False: Gram positive have a thick peptidoglycan wall
What is the building block for producing peptidoglycans in Gram positive bacteria, what is it made from
Lipid II/ N-acetyl glucosamine (NAG), N-acetyl muramic acid (NAM), Stem (penta) peptide
What is the most important amino acid in peptidoglycan
Alanine
T/F: Peptidoglycan sugars cross link to create polysacchride chains
False: Peptidoglycan peptide tails cross link with each other to create polysacchride chains through creating peptide bridges
What does transpeptidase do
Catalyzes crosslinkages in peptidoglycans
What is a B-lactam group
four membered cyclic amide
What are the drug classes that use Beta lactam grous
penicillin, cephalosporins, carbapenenms and monobactams
What is the mechanism of action for Beta-lactam antibiotics
TPase misidentifies Beta-lactam strucutre as D-Ala-D-Ala bond and then binds covalently making it irreversibly inactive
What is a structural difference of Penicllin G, what does it work best against, how is it administered
Beta-lactam ring fused to a thiazolidine ring, gram-positive bacteria, IM or IV
What is the precursor for many different manufactured Beta-lactam antibiotics
6-aminopenicillanic acid (6-APA)
What were changes to Beta-lactam antibiotics that allowed them to become orally available, what are they
Electron withdrawing side chains decrease the rate of acid hydrolysis/ amoxicillin and cloxacillin
What were penicllin improvements that allowed attack of gram negative bacteria/ what are examples of this
Slight polar side chains allowed entry through porins (-NH2 or COOH)/ Ampicillin, Amoxacillin, Carbenicllin
What are Beta-lactamases
Enzymes that hydrolyze amide bond in Beta-lactam rings
What are improvements in penicllin that allows resistance to Beta-lactamases, what are examples
Bulky side chains hinder access/ Methicillin and Cloxacillin
What is the MOA of Beta-lactamase inhibitors/ what are some examples
posses a Beta lactam ring and inactivate the enzyme without being degraded/ clavulanic acid, sulbactam, tazobactam
What is a starting compound for semisynthetic cephalosporins
7-aminocephalosporanic acid (7-ACA)
T/F: The first generations of cephalosporins are mostly active agains gram positive coccie and streptococci
True
T/F: Third generation cephalosporins have good activity against gram positive and gram negative pathogens
False: Third generation cephalosporins have better activity for gram-negatives and somewhat reduced activity against gram-positive pathogens
What does the cephalosporin moxalactam do in order to resist Beta-lactamases
Bulky side chains
T/F: Carbapenems are only good against Gram-positive
False: Carbapenems have good activity against gram positive and gram negative bacteria
T/F: Carbapenems are only used IV
True
What are other types of cell wall inhibitors that are not Beta-lactams
Fosfomycin, Bacitracin, Vancomycin
What is the MOA of bacitracin, why is it only for external barriers
Interfers with dephosphorylation of the lipid carrier that moves the peptidoglycan presursors across the cytoplamic membrane, also interferes with mammalian cells
T/F: Vancomycin is a glycopeptide and is active against gram positive bacteria
True
What is the MOA of vancomycin
Binds D-Ala -D-Ala residues at the end of the peptioglycan precursor lipid II, therefore not allowing Transpeptidase to catalyze cross linking of strands
What is improved version of Vancomycin, how is it improved
Televancin, has an additional hydrophobic side chain and a polar phosphate group binding the cell membrane and increasing the membrane permeability
What gene causes vancomycin resistance, what change does it cause
VRSA, replaces D-Ala-D-Ala for D-Ala-D-Lactate
T/F: Vancomycin can be used in treatment of infections that are methicllin and cephalosporin resistant
True
T/F: Monobactams (Aztreonam/Azactam) was developed as narrow-spectrum antibiotic targeting aerobic gram-negative bactera. It can be used in those allergic to Penicillin
True
