Lecture 17 - Antimicrobials III Flashcards
Antimicrobials that bind to 30s ribosomal subunit
Aminogycosides, tetracyclines
Antimicrobials that target 50s ribosomal subunit
Chloramphenicol, macrolides
What does chloramphenicol target?
Peptidyl transfer
What do macrolides target?
Translocation
What does mupirocin target?
Isoleucyl tRNA synthesis
What do oxazolidones target?
Formation of initiation complex
What was the first aminoglycoside?
Streptomycin
What is tobramycin good for?
Treating pseudomonas
What is gentamicin good for?
A general-purpose anti-G- antimicrobial
Why do aminoglycosides need to be injected?
Not absorbed through epithelium, so if ingested would only be active in the GIT
How are aminoglycosides administered?
injected
Are aminoglycosides bacteriostatic or bactericidal?
Bactericidal
Stages of aminoglycodside bactericidal action
1)
2)
1) Binds 30s subunit, makes recognition of mRNA codons defective. Abnormal proteins form.
2) Abnormal proteins cause membrane to become more permeable. More aminoglycosides enter bacterium, cause complete ribosomal blockade
Why does a small amount of aminoglycoside initially enter a bacterium?
Aminoglycosides are lipid-insoluble.
Have difficulty passing through cell membrane, cell wall
What is a benefit of amikacin?
Resistant to a lot of enzymes which modify aminoglycosides, so as to inactivate them
Three types of bacteria, with respect to growth under streptomycin
1) StrS - Susceptible
2) StrR - Resistant
3) StrD - Dependent
Why are StrD bacteria dependent on aminoglycoside presence?
Ribosomes are defective. Aminoglycosides correct this defect.
Ways that aminoglycosides are modified by bacteria
1)
2)
3)
1) Phosphorylation
2) Adenylation
3) Acetylation
Methods of microbial resistance to aminoglycosides 1) 2) 3) 4)
1) Efflux
2) Modified outer membrane leading to reduced entry
3) Enzymatic modification of aminoglycoside, leading to reduced entry
4) Modified 30s subunit
Example of resistance by drug inactivation
1)
2)
1) Beta lactams by beta lactamases (hydrolysis)
2) Covalent modification - aminoglycosides, chloramphenicol