Antimicrobial Chemotherapy Flashcards
Which are the chemotherapy agents target features found in microbes?
Ribosome, cell wall (PG), nucleic acid synthesis, cell membrane
What are the types of antimicrobial agents?
Antibiotic drugs (penicillin)
Antiseptics (benzalkonium chloride)
Disinfectants (hypochlorite bleaches)
Name the two types of antimicrobial drugs
Bactericidal -> kill infecting bacteria
Bacteriostatic -> halt growth (immune system continues)
What are narrow spectrum and broad spectrum antimicrobial drugs?
NS: against limited subset of bacteria
BS: against wide range of bacteria
What are the two types of chemotherapeutic drugs?
Synthetic drugs (sulphonamides) -> lab synthesized
Antibiotics (penicilllin) -> natural products
What are the types of inhibitors (antibiotic classes)
Inhibitors of cell wall biosynthesis
Disruptors of membrane function
Inhibitors of nucleic acid synthesis
Inhibitors of protein synthesis
Inhibitors of metabolism
What type of inhibitor are beta-lactams?
Cell wall biosynthesis inhibitor
True or false: penicillin attacks transglycosylase
False: penicillin attacks transpeptidase
What is the mechanism of inhibition of beta-lactams?
Target cell wall biosynthesis (transpep.)
inhibit NAM NAG crosslinking
Explain glycopeptides
Prevent NAM-NAG to be in mesh
Targets substrates not enzymes
Unable to penetrate OM of g.-
What do the two types of vancomycins do?
A: Uncrosslinked strands of pre-existing PG
B: Lipid II substrate before polymerisation into PG
True or false: Vancomycin can act on g.+ and g. -
False: Vancomycin can only act on g.+
True or false: beta-lactams can act only on g.-
False: beta-lactams can act on g.- and g.+
Explain colistin’s (polymyxins) disruption of membrane function
Target LPS in g.- (destabilises LPS)
Not absorbed by GI so must be topical or IV
What type of inhibitor is Rifampicin?
Nucleic acid (transcription) inhibitor
What does Rifampcin do?
RNA pol. inhibitor
Blocks transcription elongation (initiation)
What type of inhibitor are Quinolones?
DNA gyrase inhibitors
What are two types of Quinolones?
Nalidixic acid (g.-)
Ciprofloxacin (broad)
True or false: Drugs have high binding affinity for 70S with low affinity for 80S
True
What type of inhibitors are aminoglycosides?
Protein synthesis inhibitors
What does Streptomycin (aminoglycoside) do?
High affinity to 16S rRNA of 30S
Inhibit formation of ribosomal initiation
What do tetracyclines (aminoglycoside) do?
Bind to 16S rRNA of 30S subunit and block A-site in 70S ribosome
What do macrolides (aminoglycoside) do?
Inhibit 50S subunit
Blocks elongating peptide exit tunnel
How does one determine mechanism of action?
Seeing what drug is binding to (biochemical ligand binding assay)
Whole genome sequencing
If it is inhibiting ribosome or inhibiting cell wall
What are the types of resistance mechanism?
Keep antibiotic outside cell
Modify/mutate molecular target of antibiotic
Destroy/inactivate antibiotic
Describe the destroy/deactivate antibiotic resistance mechanism
Modify/destroy antibiotic with offensive enzymes
Describe the modify/mutate molecular targe of antibiotic resistance mechanism
Change structure of ribosomes for ribosome inhibitors so they can’t be bound
What are beta-lactamase enzymes?
Hydrolytic enzymes that destroy beta-lactam antibiotics
From what did beta-lactamase evolve from?
PBP (transpeptidases)
In what ways are beta-lactamase and PBP’s similar?
Amino acid sequence similarities -> transpeptidase similar
Gene duplication + mutational remodeling
What are the types of spread of AMR genes?
Transformation (free DNA)
Transduction (bacteriophage)
Conjugative transfer (plasmid/transposon)
How does antibiotic resistance spread?
Spread HGT of pre-existing resistance genes
in situ evolution of new resistance genes
Describes Kirby-Bauer disc diffusion assay
Growth inhibited until Minimum Inhibitory Concentration (MIC)
Use of Mast rings
Why is keeping PABA free medium important?
For microbial growth
Antibiotic diffuses (3D)
What is a clinically susceptible organism?
High likelyhood of therapeutic success
What does MIC determine?
Whether a given strain is susceptible or resistant to antibiotic
What is MBC?
Minimum bactericidal concentration
Lowest concentration of antimicrobial that will kill test organism
