Question | Answer |
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 |