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MICABI - Exam 1

Lecture 3

Drug that are cell wall synthesis inhibitors (4) Penicillins, Cephalosporins, Vancomycin, Daptomycin
Drugs that are inhibitors of protein synthesis (4) Aminoglycosides, chloramphenicol, macrolides, tetracyline
Drugs that are antimetabolites (2) Sulfonamides and Trimethoprim
Drugs that affect membrane permeability (2) Polymyxin B, Gramicidin
Drugs that affect DNA replication & repair Fluroquinolones
Gram-positive bacteria structure features Cytoplasmic membrane, thick peptidoglycan, capsule, pilus, teichoic acid
Gram-negative bacteria structure features Cytoplasmic membrane, periplasmic space, thin peptidoglycan, out membrane with porins, capsule, pilus
cell wall feature that gives rigidity, maintains the balance of osmotic pressure and keeps bacterium from lysing peptidoglycan
Bacteria cell wall made of this kind of sugar linkage alpha 1,4-glycosidic linkages
bacteria specific peptide linkage D-Ala-D-Ala peptide linkage (links nearby sugars)
first stage of baterial cell wall synthesis Formation of UDP-AMP inside the cell
function of UDP-AMP cross-linker unit
second stage of bacterial cell wall synthesis Transfer of UDP-AMP through the membrane with modification and linkage to the cell wall
Vancomycin works on this stage of cell wall synthesis second stage (addition of the single unit - UPD-AMP - linkage to the cell wall)
third stage of bacterial cell wall synthesis Once inserted into the wall cross-linking reactions and modification of the wall components
Penicillins and cephalosporins work on this stage of cell wall synthesis third stage (peptide cross-link formation between carbohydrate polymers)
how does vancomycin bind to D-Ala-D-Ala via hydrogen bonds
polypeptide antibacterial inhibitors are active against which organisms they are only active against gram-positive (dont get taken up by gram-negative membrane very well)
polypeptide antibacterial inhibitors (3) Vancomycin, Teicoplanin and Bacitracin
Van A resistance gene confers resistance to vancomycin and teicoplanin is inducible and most likely on a transferable plasmid
Van B & C resistance genes confers resistance to vancomycin only - Van B is chromosomal and non-transferable
in high level resistance, D-Ala-D-Ala peptidoglycan gets replaced with this D-Ala-D-lactate
new drug (lipopeptide) that is bactericidal to resistant gram positive pathogens Daptomycin
Daptomycin currently approved for this use Complicated Skin and Skin Structure Iinfections (CSSSI)
Daptomycin mechanism Binds irreversibly to the cytoplasmic membrane, depolarizes the membrane in a calcium dependent manner
Daptomycin is a potent bactericidal against these gram positive resistant organisms VRE and MRSA
Penicillins and Cephalosporins (B-lactams) mimick this peptide D-Ala-D-Ala
B-lactams are these types of enzymes PBP 1a & 1b - transpeptidases
B-lactamases may have evolved from these penicillin binding proteins (PBP)
bacterial strains deficient in this, are susceptible to inhibition of transpeptidase, but not lysis autolysin
3 factors determining activity of Cephalosporin or Penicillins 1) Binding affinity for target enzymes 2) Ability to penetrate the outer membrane envelope 3) Sensitivity to inactivation by b-lactamase
two main components of beta-lactam antibiotic structure Thiazolidine ring and Beta-lactam ring
Broad spectrum antibiotics are based on this ability ability to penetrate the gram-negative cell membrane
Penicillins Group I and II spectrum Narrow Spectrum
natural penicillins (narrow spectrum) Penicillin G, Pen V
Penicillins Groups III and IV spectrum Broad Spectrum
broad spectrum penicillins (2) ampicillin and amoxicillin
only class of penicillins that have activity against pseudomonas ureidopenicillins (group V)
two main components of cephalosporin antibiotic structure Dihydrothiazine ring and beta-lactam ring
in which type of bacteria are beta-lactamases a problem gram-negative bacteria
beta-lactamase resistance is due to this mechanism hydrolyzing the lactam ring
where is beta-lactamase in gram-positive bacteria excreted out into the environment (gets diluted, so less likely to hydrolyze the lactam ring)
where is beta-lactamase in the gram-negative bacteria sitting in the periplasmic space (chances of the drug getting hydrolyzed are much higher)
high conservation between these bacterial enzymes suggests common ancestry beta-lactamases and the D-Ala carboxypeptidases
MRSA determined by this chromosomal gene transferred by transduction (requires penicillinase plasmid)
supplementary PBP's acquired in MRSA have this lowered affinity for methicillin and other b-lactams
drug of choice for MRSA infections Vancomycin (with rifampin in life threatening cases)
b-lactamase Inhibitors Tazobactam and clavulanic acid
Tazobactam latest beta-lactamase inhibitor developed has the same mechanism as clavulanic acid but is more potent
Created by: Krafty