10 Stop the prokaryotes Flashcards
Targets for Chemotherapy
Class I
- Carbon sources used to produce simple compounds
- Similar mechanisms in prokaryotes and eukaryotes
- Bacteria can utilise alternative carbon sources
Targets for Chemotherapy
Class II
- Class I products used to make small molecules
- Different pathways exist in prokaryotes and eukaryotes
- Same pathways may have differing sensitivity
Targets for Chemotherapy
Class III
- Small molecules assembled into larger biomolecules
- Every cell must make it’s own biomolecules
- Distinct differences between prokaryote and mammalian pathways
- Best target for chemo
Folate Synthesis
folate synthesis can be targeted at any point it will prevent bacteria going through normal FS pathway
Synthesis of Peptidoglycan Occurs in Three Phases
Assembly of the precursor inside the cytoplasm
Transport across inner membrane
Polymerisation occurring in the periplasmid space
Nucleic Acid Synthesis
- Inhibit nucleotides
- Alter base-pairing properties of template
- Inhibit DNA or RNA polymerase
- Inhibit DNA gyrase (topoisomerase II)
Infection and therapy are..
dose related
MIC
Min inhibitory conc
MIB
Min bactericidal conc
Antimicrobial agents directed against targets
Protein synthesis - aminoglycosides and tetracyclines inhibit 30S RNA
Macrolide’s, chloramphenicol and clindomycin inhibit 50S RNA
Various mechanisms of resistance bacteria have developed
Bacteria either have or will develop genetic resistance to all known antimicrobial agents
5 main mechanisms that bacteria use to resistant antibacterial drugs are:
- Site of action - eg enzymes, ribosomes or cell wall precursors can be altered. this may include acquiring a plasmid or transposon that codes for a resilient dihydropholate reductaste
this confers trimetthrim resitance on certain bacteria
- The inhibited steps can be bypassed
- Bacteria can reduce intracellular con of that antimicrobial agent either by reducing membrane permeability by iso or my active efflux of the agent (increasing how much you pump it out)
- Alternatively they could inactivate the drug. bacteria tat could use b lactamase that destroys the penicillin lactam ring itself
- Target enzyme can be overproduced by that bacterium. In order to have the required effect the dose of the antimicrobial effect would need to be increased significantly. In doing so there is potential risk of toxicity to the patient
Biochemical targets
Synthesis of peptidoglycan, proteins and nucleic acids