Antibiotic Action Flashcards
Modern medicine relies on antibiotics for?
Surgery and transplantation
Prophylaxis and treatment
Dentistry
What is selective toxicity?
Infective organism is selectively inhibited without damaging host
Exploits difference in structure and metabolic features
Two modes of antibacterial action
Bacteriostatic- cell growth stops
Bactericidal- kills Bacterial cells
What is steric hindrance
Interfere with reactions by altering enzyme responsible
Modes of antibiotic inhibition?
1) protein synthesis inhibition
2) cell wall biosynthesis inhibition
3) inhibition of nucleotide biosynthesis/folate synthesis
2 drug types which attack nucleotide metabolism
Trimethoprims
Sulpha drugs
Both inhibit formation of tetrahydrofolate an essential component of DNA
What Antibiotics target microbes
Macrolides Lincosamides Streptogramins Oxazolidinones Aminoglycosides Chloramphenicol
Aminoglycosides
Tetracyclines
50s
30s
Describe Mupirocin?
It’s mode of action
Effective against g+ve
Inhibits isoleucine tRNA synthase
Competitive inhibitor
Selective toxicity due to SNP between histidine 581 which is serine or arginine in eukaryotes
Mupirocin binds 8000x more effectively to Bacterial enzymes than isoleucine.
Describe Linezolid?
An oxazolidinone
Bacteriostatic
Active against g+ve removed by effluent in g-ve
Binds to 50s ribosome subunit
Interferes with aa-tRNA at acceptor site
Describe Tetracycline?
Mode of action
New generation?
Family of naturally occurring and semi synthetic compounds
Core tetracycline structure
Potential to add chemical groups to top of core cyclic rings
Broad spectrum agents
Binds to 16s rRNA of 30s subunit via hydrogen bonding network
Prevent aa-tRNA associating to ribosome
Tigecycline recently developed and solves resistance problem of previous tetracyclines
Aminoglycosides mode of action
Binds to 30s only/ and 50s cause conformational change that affects positions of mRNA codon and aa-tRNA
Causing misread proteins hay imbedd into cell membrane causing destabilisation and cell death
Aminoglycosides structure is?
3 ring structure
Amino-hexose
Amino-cyclitol
Amino-hexose
Macrolides mode of action?
Binds to 23s rRNA at peptide exit site in 50s subunit
Different macrolides bind to different places
Block exit of growing peptides in the 50s subunit tunnel
Causes premature dissociation of the peptidyl-tRNA from P-site
Macrolides structure
Macrocyclic lactose ring with two sugars attached
14-16 members ring compounds produced by streptomyces
Azalides 15 ring
Ketolides 14 ring
What is azithromycin
An azalide
World most popular antibacterial agent
Deals with H. Influenza
And Moraxella catarrhalis
Structure of steptogramins
Mode of action?
Synergistic drug
Comprises of two structurally unrelated molecules group and group b
Binds to 50s subunit
A–> prevents position of peptidyl-tRNA at P site, inhibits bond formation
B–> inactivated peptidyltransferase
What is Synercrid
A streptogramins
Composed of Dalfopriatin (A) And Quinupristin (B)
Both bind to 50s subunit
What are Lincosamides?
Not commonly used
Small group of antimicrobials only Clindamycin and lincomycin developed for clinical use
Binds to 50s subunit preventing peptide bond formation
Describe Fusidic acid
Steroid like antibiotic
Interferes with release of Ef-G from ribosome
Is and accessory protein needed for ribosomal translocation
Moves ribosome via ratchet mechanism
Recognises EF-G in bound state
Retains EF-G at bound state in A site
Fusidic acid binds to hinge are of EF-G
Which classes of Antibiotics target final stages of cell wall synthesis?
Beta-lactams
- penicillin
- cephalosporins
Glycopeptides
- Vancomycin
- Teicoplanin
Mode of action of beta lactams
Structural analogues for D-ala-D-ala
Compete for binding to PBPs
Undergo nucleophilic attack by the PBPs to lead to irreversible acetylation b-lactam so permanently bind to PBPs
Are bactericidal
Cross linking of peptides is blocked
What are Beta-lactamases
Enzymes that can confer resistance to B-lactams
4 classes
A, C, D are serine lactamases
B are Metallica-enzymes-use zincions
Evolutionary related to transpeptidase
How to protect against beta-lactamases
Serine lactamases inactivated by Clavulanic acid
What is vancomycin?
Mode of action?
Interferes with transglycosylation
Doesn’t bind to PBP buns to stem peptide D-ala-D-ala
Large molecule
Forms hydrogen bond with with D-ala-D-ala thus causing steric hindrance
Vancomycin binds to lipid 2 on the outside of the inner membrane this stops cross linking of peptidoglycans and incorporation into wall
Inactive against gram-ve as to large
What is Fosfomycin?
Antibiotic rather small
Natural product- 3 ring episode
Bactericidal
Acts on first step of PG synthesis
Binds covalently to essential cysteine residue at active site of MurA
Cycloserine?
Small broad spectrum agent
Structural analogy to D-alanine
Competitive inhibitor of alanine race made and D-alanyl-D-alanyl ligase
