β-lactam containing compounds bind to and inhibit ______________. - ANSWERSTranspeptidases.-Bind to transpeptidases much stronger than D-Ala-D-Ala.- Binding is covalent and irreversible and results in inhibition of the enzyme, cell wall synthesis, and consequently death by cell lysis
Novobiocin...
AMR Final Exam 100% Correct!!
β-lactam containing compounds bind to and inhibit ______________. -
ANSWERSTranspeptidases.-Bind to transpeptidases much stronger than D-Ala-D-Ala.-
Binding is covalent and irreversible and results in inhibition of the enzyme, cell wall
synthesis, and consequently death by cell lysis
Tetracyclines - ANSWERS- Isolated from soil-dwelling streptomyces
-Broad spectrum: effective against G(-)/(+), intracell bact (rickettsias, chlamydias)
-Most widely used antibiotic in ag
Chloramphenicol - ANSWERSIsolated from streptomyces
Broad-spectrum
small size allows diffusion
serious side effects
Quorum sensing inhibitors - ANSWERSMOA:Disrupt intercell signaling between
bacteria to block coordinated tissue invasionBenefits:Blocks sensing of necessary
concentrations of bacteria for optimal synthesis of virulence and invasion genes
Treatment of citrus greening disease uses clinically important antibiotics. What
antibiotics are they? - ANSWERSStreptomycin and tetracycline
Penicillin G, V, and Methicillin
broad or narrow - ANSWERSnarrow
Ampicillin and amoxicillin
broad or narrow - ANSWERSbroad
How many classes are there of β-lactam antibiotics? What are they? - ANSWERS5
1. Penicillins (mold)
2. Cephalosporins (mold)
3. Carbapenems (bacteria)
4. Monobactams (bacteria)
,5. Clavams (bacteria)
Bacitracin - ANSWERS- Margaret Tracy
- Found to physically bind to C-55-isoprenyl pyrophosphate and inhibit its
dephosphorylation
- Kidney toxicity: topical use only- Approved by FDA for use in ag (poultry)
C-55 isoprenyl pyrophosphate (flippase) - ANSWERS- Facilitates transport of lipid II
across bacterial membrane- Recharged against by dephosphorylation and is shuffled
back into the cytoplasm
_______________ inhibits cell wall synthesis through a mechanism that is distinct from
β-lactam and vancomycin. - ANSWERSBacitracin
Cycloserine - ANSWERS- Cell wall synthesis inhibitor
- D-alanine analog
- Small size --> penetrate membrane of G(-) bacteria: broad spectrum
- Restricted as secondary choice for MDR-Tb and XDR-Tb
D-cycloserine works ____________ of β-lactams, vancomycin, and bacitracin through a
very distinct mechanism - ANSWERSupstream
Fosfomycin - ANSWERSCell wall inhibitor
Highly reactive epoxide ring with broad-spectrum bactericidal properties
Inhibits MurA
Fosfomycin enters the cell via __________ _____________ or the glycerophosphate
transporter - ANSWERShexose monophosphate
Fosfomycin inhibits ___ steps of bacterial cell wall biosynthesis in the bacterial
cytoplasm. - ANSWERSearly
Dihydrofolate reductase (DHFR) - ANSWERS- An essential enzyme in both proks and
euks
- Converts dihydrofolate back into tetrahydrofolate that is converted into methylene-
tetrahydrofolate by a serine transhydroxymethylase
MurA - ANSWERSEnzyme that catalyzed add'n of enolpyruvated to UDP-N-
acetylglucosamine
Methotrexate inhibits ___ - ANSWERShuman DHFR
,cancer treatment/ immunosuppresent
Trimethoprim - ANSWERS- Bacteriostatic
- ~100,000 fold selectivity for bacterial DHFR
- Broad-spectrum antibiotic commonly prescribed to treat MRSA (always in combo)
Folate synthesis in bacteria requires - ANSWERSdihydropterin and PABA
Sulfanilamide is a drug that mimics... - ANSWERSPABA
Sulfa drugs - ANSWERScompetitive inhibitors of dihydropteroate synthase
prodrug prontosil
Cotrimoxazol - ANSWERS- Antimicrobial that combines a sulfa-drug (DHPS inhibitor)
with trimethoprim (DHFR inhibitor)
- Less chance for developing resistance
- Provides synergistic effect
When taken alone, trimethoprim and sulfamethoxazole are bacteriostatic, but when
combined they become __________. - ANSWERSbactericidal
Para-aminobenzoate synthesis: - ANSWERS- ADC synthase and lyase facilitate the
synthesis of PABA
- Abyssomicin C is a recently-discovered antibiotic that inhibits ADC synthase
Quinolone antibiotics - ANSWERS- Antimicrobial activity (Nalidixic acid)
- Characterized by a 4-quinolone bicyclic ring
- Type 2 topoisomerase inhibitor: gyrase and topo 4
Ciproflaxin - ANSWERS- Fluoroquinolone: broad-spectrum bactericidal antibiotic
- Most widely used antibiotic
Targets of quinolones: - ANSWERS- DNA gyrase (type 2 topoisomerase)
- Topoisomerase 4
DNA gyrase (type 2 topoisomerase) - ANSWERS- An enzyme responsible for
introduction of negative supercoils into DNA
- Heterotetrameric (GyrA and GyrB)
GyrA: - ANSWERSmediates enzyme-catalyzed DNA breakage-reunion
GyrB: - ANSWERSATPase activity and facilitates strand passing
, Fluoroquinolones bind to ______ and ________ subunits. - ANSWERS- ParC
(breakage-reunion subunit)
- GyrA
Topoisomerase 4 - ANSWERS- Paralogue of DNA gyrase
- Facilitates DNA strand passing
- Relaxes (+) supercoiled DNA
- Heterotetrameric (ParC and ParE)
Metronidazole - ANSWERS- Synthetic derivative of parasitic drug produced by
Streptomyces repurposed in 1962
- Prodrug: Activated by anaerobic bacteria, leading to formation of DNA adducts
- Class: Nitroimidazoles
Metronidazole is active against: - ANSWERSAnaerobic bacteria (C.diff, H.pylori,
bacterial vaginosis etc)
_______________ is non-specific and irreversible covalent binding to DNA leads to cell
death. - ANSWERSMetronidazole
Rifampin specifically binds to bacterial __________ ____________ and prevents RNA
synthesis. - ANSWERSRNA polymerase
Rifampicin - RNAP complex - ANSWERS- Crystal structure of RNA polymerase bound
with rifampicin molecule
- Rifampicin directly binds in the path of the elongating RNA molecule by a simple steric
block
In bacteria, the start codon AUG corresponds to formylmethionine, rather than
methionine. fMet is removed post-translationally. Its presence in humans indicates
presence of ___. - ANSWERSforeign bodies
Streptomycin, Neomycin, Kanamycin, and Gentamicin are all examples of... -
ANSWERSAminoglycosides
Aminoglycosides given in combination with β-lactam become.... -
ANSWERSbactericidal
Aminoglycosides' amino group is ___ charged at neutral pH, which allows them to
interact with ___ charged phosphate backbone. - ANSWERSpositive
negative
Binding of aminoglycosides to 30S ribosomal subunit leads to inhibition of _______
translocation from A to P site and causes misreading of mRNA - ANSWERStRNA
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