M: Antibiotic Action - week 9 Flashcards
What may antirmicrobials be directed against? (5)
bacteria, viruses, fungi, protozoa and helminths (so basically everything)
Name 4 subsets of antimicrobials
- antibiotics (antibacterial, so don’t work on viruses)
- antivirals
- antifungals
- antiparasitic drugs
What status of organism (i.e. quiescent or replicating) are antimicrobials directed against
Replicating organisms
What 4 ways can we classify antibiotics?
- Source
- Chemical structure (where name often comes from)
- Spectrum (whether broad or narrow)
- Broad mechanism of action (what they target and whether they are bacteriocidal or bacteriostatic)
What types of antibiotics are there and how are they derived? (3)
Natural: naturally, from moulds and bacteria
Semi-synthetic: natural, chemically modified
Chemotherapeutic agents: chemicals, synthetic
What is the reasoning behind adding a side chain to the base penicillin to create a penicillin variant?
For increasing resistance by stopping the activity of B-lactomase, which cleaves the molecule.
Why would you prefer a narrow spectrum of antimicrobial action over a broad spectrum? (2)
- the more organisms you attack the more likely one will develop resistance
- a broad spectrum can harm normal microbiota and cause problems that way
Provide 2 examples of bacteriostatic antibiotics
- chloramphenicol
- erythromycin
Provide 2 examples of bactericidal antibiotics
- aminoglycosides
- beta-lactams
Why might you decide to give bacteriostatic antibiotics rather than bactericidal? When might you not want to use bacteriostatics?
To give your immune system time to fight the bacteria. So don’t want to use in immunosuppressed people
How do bacteriostatics effect bacterial growth over time? How do bactericidals differ?
Growth is stopped however the bacteria are still viable and the viable bacteria count has not stopped.
Bactericidals actually remove/kill the viable bacteria
Name the 3 key considerations for antimicrobial action i.e. the 3 factors that determine whether an organism will be ‘sensitive’ or ‘resistant’ to the antimicrobial in question
- Selecive toxicity: want to target the organism, not the humans
- Access to site of infection: achieve adequate levels to where the organism is
- Provision of appropriate levels for an appropriate time: maintain adequate levels to allow inhibition or killing
How is selective toxicity achieved?
by exploiting the differences in the structure and metabolism of the bacterium and host cells
Name 6 classes of antimicrobials (S4) used by registered optometrists in ocular infections
- Beta Lactams
- Aminioglycosides
- Quinolones
- Macrolides
- Tetracyclins
- Cyclic Peptides
Note there are a few others i didn’t mention here, which can count as an answer for this question: chloramphenicol, rifamycins, glycopeptides, nitroimidazoles, nucleoside analogues
Name 4 antibacterial agents that act on peptide synthesis of the bacteria
- Macrolides
- Chloramphenicol
- Tetracyclines
- Aminoglycosides
Remember by: MCAT
Name 2 antibacterial agents that act on peptidoglycan synthesis of the bacteria
- beta lactams (e.g. penicillins, cephalosporins)
- glycopeptides (e.g. vancomysin)
Remember by: the BGs
Name 1 antibacterial agent that acts on cell membrane synthesis of the bacteria
Polymyxins
Name 2 antibacterial agents that act on folic acid of the bacteria
- Trimethoprim
- Sulphonamides
Name 1 antibacterial agent that acts on nucleic acid replication of the bacteria
- Quinolones
Name 1 antibacterial agent that acts on RNA synthesis DNA-dependent RNA polymerase
Rifamycins
Compare how antimicrobial agents diffuse through gram +ve vs gram -ve bacteria. Which one is easier to diffuse through? Why?
Gram +ve bacteria is easy/easier for antimicrobial agents to diffuse through the outer wall/membrane; With Gram -ve, the membrane stops entry and so the agent must go through the narrow channels (porins) to access the peptidoglycan
Describe the structure of peptidoglycan (4)
is a polymer consisting of sugars and amino acids. The sugar component consists of alternating residues of beta-(1,4) linked NAG and NAM. Attached to the NAM is a peptide chain of 3-5 amino acids. This peptide chain can be cross-linked to another peptide chain of another strand to form a 3D mesh like layer
What do NAG and NAM stand for?
NAG = N-acetylglucosamine
NAM = N-acetylmuramic acid
What is a peptide chain called when it consists of 5 amino acids?
A “pentapeptide”
Name 5 things that cell wall synthesis requires (for it to grow and extend)
- production of peptidoglycan monomers inside the cytoplasm
- transport across the membrane (via a carrier molecule with 2 phosphate groups on it)
- cleavage of existing peptidoglycan by autolysins (peptidases) and joining of new monomers
- peptide cross-linking, which occurs by “transpeptidation” by transpeptidases
- continual remodelling needed due to regular binary fission
What is “transpeptidation”? What transpeptidation takes place for peptide cross-linking?
A chemical reaction where an amino acid residue or peptide residue is transferred from one amino compound to another.
For cross linking: Addition of Gly-Gly-Gly-Gly-Gly
Roughly describe how cell wall synthesis occurs (5 steps)
- NAM with pentapeptide on it gets picked up by a carrier with one phosphate on it and goes through a process
- The carrier (with NAM and pentaphosphate) then picke up another phosphate and NAG, which makes it the “Monomer”
- Monomer on carrier with 2 phosphates travels across membrane
- Once there, NAM and NAG get delivered and incorporated into the peptidoglycan (of the wall)
- Carrier molecule loses a phosphate and gets recycled to do this again
How do beta-lactams work? Explain their structure, what they bind to and what effect this has when bound (3)
Beta-lactams act as a structural analogue of D-alanyl-D-alanine (D-ala-D-ala), which are the terminal amino acid residues on the precursor NAM/NAG peptide subunits of the peptidoglycan layer of the cell wall
- as a consequence, they bind to the active site of PBPs (i.e. DD-transpeptidases) and inhibit these transpeptidases. They also inhibit enzymes involved in remodelling the cell wall
What is the net result of using beta-lactams
inhibition of cell wall synthesis
What does PBP stand for?
Penicillin Binding Protein
Do all bacteria have the same PBP?
No. different bacteria may have different PBPs
What does the spectrum of activity of a particular beta-lactam depend on?
depends on whether the antibiotic binds to the different PBPs found in the organism
Name an example of a beta-lactam
Penicillin
Name 3 classes of drugs used to inhibit cell wall synthesis
- Beta-lactam antibiotics
- Glycopeptides
- Bacitracin
What class of drug is vancomycin? How does it work? How does it compare to beta-lactams? What is the outcome? (4)
it is a glycopeptide. it binds to terminal D-ala-D-ala residues in a slightly different way to beta-lactams.
- therefore it prevents incorporation of the NAM-NAG subunit into the growing peptidoglycan chain which therefore inhibits cell wall synthesis
How does the binding of vancomycin differ from beta-lactams?
vancomycin binds/acts on the final D-ala directly whereas beta-lactams inhibit the transpeptidases directly by being a D-ala-D-ala structural analogue
Both inhibit transpeptidase action on D-ala-D-ala but in different ways as described above
In regards to Bacitracin, describe the following:
A: its structure
B: when it acts
C: what it does
D: final outcome
Bacitracin
A: is a cyclic polypeptide
B: acts after the NAG-NAM subunit has been added to the peptidoglycan chain
C: prevents dephosphorylation of the phospholipid carrier, which prevents regeneration of the carrier of the subunits
D: inhibition of peptidoglycan/cell wall synthesis
State how Bacitracin is administered and why (1). What type of microorganisms is Bacitracin effective on?
Bacitracin is only administered topically, due to significant toxicity.
It is effective against Gram +ves and some Gram -ves
List 3 outcomes of cell wall synthesis inhibition (sequentially)
- bacteria continue to grow
- cell wall becomes weakened
- bacteria lyse
Describe the effect of peptidoglycan synthesis inhibition on binary fission
Cell wall no longer grows to accommodate the growing bacteria and a gap is formed. Bacteria squeezes through the gap in the cell wall and the cell wall breaks apart, leaving a single “spheroblast”, which is a bacteria with no cell wall, leaving it vulnerable to being lysed. Which is what happens
Name 3 targets that antimicrobial agents can act on to kill bacteria. Provide an example agent for each
- peptidoglycan synthesis (Cell wall) - e.g. Bacitracin
- cell membrane synthesis - e.g. Polymyxin B
- peptide/protein synthesis - e.g. aminoglycosides, tetracylcines, chloramphenicol, macrolides, mupirocin
In regards to Polymyxin B:
A: Describe its structure
B: What is its target to act on?
C: How does it act on its target?
D: What type of organisms is it effective against?
E: How toxic is it?
A: cyclic peptides
B: cell membrane
C: it interacts with cell membrane phospholipids: altering permeability and causes leakage of intracellular components
D: effective against Gram -ves and also fungi
E: is HIGHLY TOXIC.
How does the level of polymyxin B’s toxicity influence administration?
Since it is highly toxic, it is for topical use only
Name the 3 steps of polypeptide synthesis (protein synthesis)
- Initiation
- Elongation
- Termination
Describe the initiation step of polypeptide synthesis (4)
Protein synth begins when the mRNA to be translated associates with the initiating tRNA on the 30s ribosome. The 50s subunit then associates with the 30s subunit to form the ribosome
Describe the elongation step of polypeptide synthesis (4)
the ordered polymerisation of the amino acid chain. Binding and recognition of new tRNAs which carry individual amino acids occurs. Peptide bonds are formed between the amino acids, and the mRNA moves through the ribosome as more amino acids are added
Describe the termination step of polypeptide synthesis (1)
when a stop codon is reached
Provide an example of an antibiotic that works on the following parts of protein synthesis:
- initiation
- peptidyl transfer
- translocation
- tRNA synthesis
initiation: aminoglycosides, tetracyclines
peptidyl transfer: chloramphenicol
translocation: macrolides
tRNA synthesis: mupirocin
Define translocation in the context of protein synthesis
movement of the ribosome along mRNA
