Discuss Selective Killing of
Bacteria in a Mammalian Host
Intro
Selectivity is achieved by targeting compounds not found in mammalian host (cell
wall, folate synthesis) or compounds with different affinity to those in mammalian
host (DNA and protein synthesis). The host immune system achieves selectivity by
recognising non-self (antigens, PAMPs).
Killing of bacteria requires bactericidal action of drugs but some bacteriostatic drugs
will be discussed as well (protein synthesis inhibitors) since even bacteriostatic
effects can lead to killing by the host’s immune system and in high doses, the
bacteriostatic drugs can have bactericidal effects
Cell wall
Inhibiting cell wall production means normal turnover from autolysins will degrade
the cell wall and lead to osmotic lysis
Very selective since mammalian cells don’t have cell walls
NAG is converted to UDP-NAM by the addition of UDP, 3 C from PEP, D-Ala-D-Ala
D-cycloserine is a D-Ala analogue
Fosfomycin inhibits the transfer from PEP
UDP-NAM and UDP-NAG are combined
Transferred across the inner membrane by bactoprenol pyrophosphate
Bacitracin inhibits the recycling of this lipid carrier back to the cytosolic side
In the periplasm, transpeptidase (and transglycosylase) join monomers by acting on
the D-Ala-D-Ala peptide
Vancomycin binds to D-Ala-D-Ala and stops monomers bein polymerised
Resistance has formed by changing this to D-Ala-D-Lac
Penicillin mimics D-Ala-D-Ala and irreversibly inactivates transpeptidase
Discuss Selective Killing of Bacteria in a Mammalian Host 1
Bacteria in a Mammalian Host
Intro
Selectivity is achieved by targeting compounds not found in mammalian host (cell
wall, folate synthesis) or compounds with different affinity to those in mammalian
host (DNA and protein synthesis). The host immune system achieves selectivity by
recognising non-self (antigens, PAMPs).
Killing of bacteria requires bactericidal action of drugs but some bacteriostatic drugs
will be discussed as well (protein synthesis inhibitors) since even bacteriostatic
effects can lead to killing by the host’s immune system and in high doses, the
bacteriostatic drugs can have bactericidal effects
Cell wall
Inhibiting cell wall production means normal turnover from autolysins will degrade
the cell wall and lead to osmotic lysis
Very selective since mammalian cells don’t have cell walls
NAG is converted to UDP-NAM by the addition of UDP, 3 C from PEP, D-Ala-D-Ala
D-cycloserine is a D-Ala analogue
Fosfomycin inhibits the transfer from PEP
UDP-NAM and UDP-NAG are combined
Transferred across the inner membrane by bactoprenol pyrophosphate
Bacitracin inhibits the recycling of this lipid carrier back to the cytosolic side
In the periplasm, transpeptidase (and transglycosylase) join monomers by acting on
the D-Ala-D-Ala peptide
Vancomycin binds to D-Ala-D-Ala and stops monomers bein polymerised
Resistance has formed by changing this to D-Ala-D-Lac
Penicillin mimics D-Ala-D-Ala and irreversibly inactivates transpeptidase
Discuss Selective Killing of Bacteria in a Mammalian Host 1
