Title: Agents Attacking the Cell Membrane
1Agents Attacking the Cell Membrane
2Cell Membrane
Precursor biosynthesis
Respiration
15 classes including Antimycin Blastomycin Nitroi
midazole Nitrofurantoin
Triclosan Isoniazid Ethionamide Cerulenin Thiolact
omycin Naftidin Azoles
Structural integrity
Pore/channel forming Amphotericin
B Nystatin Gramicidin A Alamethicin Suzukacillin
Monazomycin Rofalomycin
Halophenols Chlorhexidines Polymixins Tyrocidin Gr
amicidin S Filipin Flavofungion Etruscomycin Defen
sins
Ionophores
13 classes including Monensin Nigericin Laslocid S
alinomycin
3Precursor biosynthesis
4Triclosan
Originally assumed to be a non-specific
antiseptic and has been widely used in household
products.
Now known to be a specific inhibitor of
enoyl-ACP reductase and that resistance can occur
through point mutation.
5Isoniazid
Selective agent for Mycobacteria. Important
part of tuberculosis chemotherapy. Recently
found to be activated by catalase to make a
specific inhibitor of enoyl-ACP reductase.
Resistance can occur through point mutations
that inactivate catalase or that decrease
affinity for target.
6Structural Integrity
7Chlorhexidine
In absence of chlorhexidine
In presence of chlorhexidine
8Gramicidin S
9Polymixin B
Cationic lipopeptide, binds to negatively charged
groups on the Gram-negative cell wall and
disrupts membrane. Resistance achieved by
enzymes that add amino-arabinose to cell wall,
increasing positive charge.
10Colistin
- A member of the polymixin family
- Use discontinued during 1980s because of
associated - nephrotoxicity
- Now being re-evaluated as a last resort for
treatment of - infections caused by multi-resistant
Gram-negative bacteria
11Pore/channel forming Peptides
12Gramicidin A
13Insect Anti-microbial Peptides
Cecropins are small amphiphilic peptides produced
by insects in response to stresses such as
bacterial infection. They work, like gramicidins
and polymixins, to collapse ion-gradients and
trigger lysis.
14Amphibian dermal secretions
Magainins are small amphiphilic peptides produced
by frogs and toads. They collapse ion-gradients
and cause lethal swelling of many bacteria.
15Defensins antimicrobial peptides of human origin
Defensins are small, soluble polypeptides
secreted by the Paneth cells located in the
invaginations of the intestinal epithelium. They
cause lysis of many bacteria
16Amphotericin B Nystatin
17Amphotericins
Macrocyclic lactones that bind to cholesterol
containing membranes to form pores. Important
anti-fungal agents
18Mobile Ionophores
19Valinomycin
Forms complex with K (Cs). Valine residues form
a hydrophobic shell arund the ion.
20Valinomycin
The free antibiotic and the lipid-soluble cation
complex diffuse freely across the membrane,
allowing the K concentration to reach
equilibrium across the membrane
21Nigericin
The free antibiotic and the lipid-soluble cation
complex diffuse freely across the membrane,
allowing the H/K concentration to reach
equilibrium across the membrane
22Monensin and Salinomycin
Salinomycin
Very similar in structure to nigericin, but form
a slightly smaller clathrate shell. Thus, more
selective for Na