Intro to Antibiotics
Objectives:
- understand the main classes of antibiotics and their mechanism of action
- discuss the molecular mechanism of antibiotic resistance
- discuss how antibiotic resistance spreads
- be a good steward of antimicrobials
Content:
what are antibiotics inhibit bacterial growth interferes with specificially bacterial enzymes differential toxicity for bacterial cells target not prentent in eukaryotic cells or target sufficiently differenyt alot of antibiotic comes from nature
bacteria targets
cell wall synthesis
Betalactams
interferes with peptidoglycan crosslinking nam and nag chains have pentapeptide which are joined by penicillin binding proteins B lactams have a b Lactam ring which are broken by penicillin binding protein and then irreversable binds to PBP gumming it up
example classes
- penicillins
- cephalopsporins
- carbapenems
- monobactams
allergy to B lactams are grossly overreported so be fastidious most commonly to penicillins most commonly to R chains and so you can prescribe diffferent Blactams
Glycopeptides (massive proteins so only gram positive)
examples
- vancomycin
- teicoplanin
mechanism they just bind to the pentapeptide chain to prevent cross linking
Polymyxins
- colistin
- polymixin b
Polymyxin structure
peptide ring with lipid part. Lipid component inserts into membrane and causes pores to form
Cyclic cationic lipopeptide
positive charge is attracted to the negative membrane inner
gram negative only as it targets the outer membrane
daptomycin
similar struction to polymyxin but only targets gram positive bacteria
Nucleic acid synthesis
Folate synthesis
sulfadrugs
sulphonamides competitively inhibits step of tetrahydrofolic acid by imitating a precursor
trimethoprim structural analogue to dihydrofolic reductase
sulphonamides and trimethoprim together often called cotramoxazole only cotramoxazole used
DNA gyrase
fluoroquinolones inhibit dna gyrase dna gyrase introduces negatove supercoils
RNA polymerase
inhibits RNA polymerase resistance can occur due to a single point mutation
Metronidazoles
prodrug
when activated breaks dna, extremely toxic
activatied by ferredoxin or flavodoxin which are only present in anaerobes and microaerophiles
Aerobes and mitochondria use NAD instead
some protozoa also use ferredoxin and flavodoxin EG giardia
protein synthesis
Functions be binding to bacterial ribosomes 16s rRNA in the 30S subunit (small bit)
- aminoglycosides
- tatracyclines 23S rRNA in the 50S subunit (big bit)
- macrolide
- lincosamindes
- oxazolidinones
Spectrum of antibiotics spectrum is bacteria that get inhibited by a certain antibiotic