BMS2052 Study Guide - Final Guide: Tooth Enamel, Cephamycin, Cytostasis
4 May 2018
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Antimicrobial Agents and Resistance
ANTIBIOTICS
Antibiotics are selective inhibitors of microbial
growth. Are all small molecules. Antibiotics
target parts of bacteria that are very different
to us.
Narrow spectrum target a very specific group
of bacteria vs broad. mostly a matter of
permeability.
Natural antibiotics are obtained by
fermentation of producer organisms.
Semisynthetic are chemically modified natural
products (B-lactams). Synthetic do not have a
natural source (quinolines).
Antimicrobials may be cytocidal for one
organism but cytostatic for another.
Antibacterial Targets
- Rifamycins: RNA pol
- Quinolones: DNA gyrase
- Aminoglycosides and tetracylines: 30S
ribosomal subunit
- Macrolides and Oxaolidinones: 50S RS
- B-lactams: cell wall (PG)
- Anti-folates: metabolism
- Daptomycine and polymyxin:
cytoplasmic membrane (for MDR/XDR
bacteria)
For G+: B-lactams, some fluroroquinolones,
macrolides, tetracylines, anti-folates
For G-: some B-lactamns, fluroquinolones,
aminoglycosides, tetracyclins, antifolates
Penicillin targets the PG by forming an
irreversible cross link with the penicillin
binding protein (the enzyme which cross-links
D-ala to D-gly. B-lactams resemble D-ala/D-
ala. This prevents cross-linking occurring. The
bacteria dies from osmotic shock. These are
ineffective against intracellular bacteria. B-
lactams include:
- Monobactams
- Penicillins (ampicillin, amoxicillin ect)
- Carbapenems
- Cephalosporins
- Cephamycin
Carbapenems are beta-lactam antibacterial
that are derived from the natural produce
thienamycin. They are broad spectrum and
resistant to most types of beta-lactamases. IV
only.
PROTEIN SYNTHESIS INHIBITORS
Ribosomal interfering antibiotics. (the normal
function of ribosomes is to translate mRNA
into proteins).
Aminoglycosides are primarily anti-gram
negative agents (aerobic), they interfere with
proof-reading process for incoming aa-tRNA
by binding to the 30s. This is allowing proteins
to be made but are nonsense – premature
termination or mutated. They are
bactericidal. They are not orally bioavailable
as they bind to our own mitochondrial
ribosomes have side effects are ototoxic
and nephrotoxic. Eg. Streptomycin,
kanamycin. Resistance through target
mutations and modifying enzymes.
Tetracyclines (doxycycline, tigecycline) bind to
the 30S RB preventing entr of aa-tRNA into
the A-site. They are broad spectrum oral
bacteriostatic agents that are active against
intracellular pathogens. They bind divalent
cations (in milk or tooth enamel). They are
excreted how they go into the body eg in
sewage problem for generating resistance
and the environment. Resistance through
efflux or ribosomal protection proteins.
Macrolides block the exit tunnel of the
ribosome by binding to the 50S RS. They
target G+ and have a long half life. They enter
and accumulate in Euk cells. Eg erythromycin
and azithromycin. Have multiple resistance
mechanisms target modification (RNA
methylation), efflux and enzymatic
modification. Erythromycin interferes with
nascent protein progression by blocking the
protein exit tunnel by binding to the large
ribosomal subunit this only allows the first
couple of aa to be joined.
Oxazolidinones are a new class – a fully
synthetic drug. They bind to the rRNA on the
A side (do not have a protein target). They are
binding exactly where tRNA would on the
Document Summary
Antibiotics target parts of bacteria that are very different to us. Narrow spectrum target a very specific group of bacteria vs broad. Natural antibiotics are obtained by fermentation of producer organisms. Synthetic do not have a natural source (quinolines). Antimicrobials may be cytocidal for one organism but cytostatic for another. Daptomycine and polymyxin: cytoplasmic membrane (for mdr/xdr bacteria) For g+: b-lactams, some fluroroquinolones, macrolides, tetracylines, anti-folates. For g-: some b-lactamns, fluroquinolones, aminoglycosides, tetracyclins, antifolates. Penicillin targets the pg by forming an irreversible cross link with the penicillin binding protein (the enzyme which cross-links. Carbapenems are beta-lactam antibacterial that are derived from the natural produce thienamycin. They are broad spectrum and resistant to most types of beta-lactamases. Ribosomal interfering antibiotics. (the normal function of ribosomes is to translate mrna into proteins). Aminoglycosides are primarily anti-gram negative agents (aerobic), they interfere with proof-reading process for incoming aa-trna by binding to the 30s.
