Antibiotic mechanism and Bacterial Resistance Flashcards
What is a anti-microbial agent? What is an antibiotic?
naturally occurring or chemically synthesised substances intended to be toxic for the pathogenic organisms but harmless to the host
- includes antibiotics. antivirals, antifungals and antiparasitics.
antibiotic
- natural substance or a derivative of a natural substance when taken in small doses will either kill or prevent the growth of bacteria but will not seriously harm the host
What are the classifications of antibiotics?
spectrum of activity
effect on organism
chemical structures
mode of action
What are the types of spectrum of activity?
broad spectrum activity
- antibiotics that are effective against a large variety of microbes
- high likelihood of destroying friendly bacteria of a patients normal microbial flora
- tetracycline
narrow spectrum activity
- antibiotics that are only effective a relatively small subset of bacteria
- penicillin
What are the different effects of antibiotics?
bactericidal
- interaction results in irreversible disruption or binding
- leads to cell death
- beta lactams
bacteriostatic
- interaction involves lower affinity binding and is reversible when the anti-bacterial is removed from the environment
- inhibit growth
- tetracyclines
What are the different modes of action?
inhibition of cell wall synthesis
- beta lactams (penicillin and cephalosporins), vancomycin
disruption of cell membrane
- nystatin, amphotericin B
inhibition of protein synthesis
- aminoglycosides, tetracyclines, chloramphenicol, lincosamides
inhibition of nucleic acid synthesis
- metronidazole, quinolone - nalidixic acid, ciprofloxacin
inhibition of metabolic pathways
- sulphonamides, trimethoprim
How is the peptidoglycan cell wall synthesised?
bacteria increase their size following binary fission
- autolysis (bacterial enzymes) break the glycosidic bonds between the peptidoglycan monomers and the peptide cross bridges that link rows of sugars together
- this is followed by insertion of new peptidoglycan monomers = enable bacterial growth
- transglycosidase enzymes catalyse the formation of the glycosidic bonds between the new N-acetyl muramic acid (NAM) and N-acetyl glucosamine (NAG) monomers and with the existing peptidoglycan chain
- transpeptidase enzymes (penicillin binding protein) reform the peptide crosslink between two rows and the layers of the peptidoglycan
What are the cell wall synthesis inhibitors? How do cell wall synthesis inhibitors work?
bactericidal
- vancomycin
- beta lactam - penicillin, cephalosporins
they bind to the transpeptidase enzymes (penicillin binding enzymes)
- weakens the bacterial cell wall
- some areas of the cell wall will be weak resulting in the cell bursting due to osmotic lysis
What antibiotics disrupt cell membrane function? inhibitors? How do these inhibitors work?
NAP
nystatin
amphotericin B
polymyxins
they bind to the lipid membrane of the cell to form pores in the membrane. this leads to
- ion leakage
- acidification
damage to the cytoplasmic membrane - increases permeability by disorganising the structure or inhibiting the function of bacterial membrane
What are the drugs that inhibit protein synthesis?
aminoglycosides - bactericidal
- streptomycin
- kanamycin
- gentamicin
tetratcylines - bacteriostatic
- tetracyclines
- minocycline
- doxycycline
chloramphenicol, clindamycin - bacteriostatic
- chloramphenicol
macrocodes - bacteriostatic
- erythromycin
Which antibiotics bind to the 30S portion of the ribosome? How do they work?
aminoglycosides - bactericidal
- irreversibly bind to the 16s rRNA and changes the shape of the 30S subunit
- change in shape causes misreading of the code on the mRNA
- affects many gram negative and some gram positive
- resistance is common
tetracylines - bacteriostatic
- bind reversibly to the 30S subunit and inhibit the binding of the tRNA to the acceptor site on the mRNA-ribosome complex
- broad spectrum
- resistance is common
- destruction of normal intestinal flora/stains teeth = not given to pregnant women/breastfeeding women (stains baby)
Which antibiotics bind to the 50S portion of the ribosome? How do they work?
chloramphenicol, clindamycin - bacteriostatic
- bind to the 50S portion and inhibit peptidyl transferase activity so no peptide bonds
- broad spectrum
- resistance is common
- chloramphenicol can be toxic = grey baby syndrome, aplastic anaemia
macrolides - bacteriostatic
- bind to the 5OS portion and stops translocation of the ribosome along the mRNA
- active against gram positive bacteria
- resistance is common
- may be an alternative to patients allergic to pencillin
What do nucleic acid synthesis inhibitors do? What are the drugs that inhibit nucleic acid synthesis?
interfere with purine (A,G) and pyrimidine (C,T,U) synthesis
rifampicin - bactericidal = inhibits RNA synthesis and function
quinolone - nalidixic acid, ciprofloxacin - bactericidal = inhibits DNA synthesis and function
metronidazole - inhibits DNA synthesis and function
How do nucleic acid synthesis inhibitors work?
inhibits RNA synthesis and function
rifampicin - bactericidal
- binds to DNA-dependent RNA polymerase and inhibits initiation of RNA synthesis
- broad spectrum
- treats tuberculosis, used in combination therapy
quinolone - nalidixic acid, ciprofloxacin - bactericidal
- bind to the A subunit of DNA gyrase and prevents supercoiling of DNA (essential for DNA replication)
- active against gram positive cocci
- treats UTIs
- resistance is common for nalidixic acid and developing for ciprofloxacin
metronidazole - bactericidal
- inhibit anaerobic bacteria and protozoa
- nitro group of metronidazole is reduced and this metabolite caused breaks in the DNA strand
- mammalian cells are unharmed as they lack the enzymes to reduce metronidazole
What do metabolic pathway inhibitors do? What are the drugs that inhibit metabolic pathway?
inhibit bacterial enzymes required for the synthesis of folic acid - tetrahydrofolic acid
sulphonamides - bacteriostatic
trimethoprim - bacteriostatic
How do metabolic pathway inhibitors work?
sulphonamides - bacteriostatic
- block thymidine (pyrimidine) and purine synthesis by inhibiting microbial folic acid synthesis
- broad spectrum
- treats UTIs
- co-trimoxazole
trimethoprim - bacteriostatic
- bind to dihydrofolate reductase and inhibit formation of tetrahydrofolic acid
- treat UTI
- treat MRSA in conjunction with rifampicin = combination therapy
