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