Polymyxin
Polymyxins are cationic detergent antibiotics, with a general structure of a cyclic peptide with a long hydrophobic tail. They disrupt the structure of the bacterial cell membrane by interacting with its phospholipids. Polymyxins have a bactericidal effect on Gram-negative bacilli, especially on Pseudomonas andcoliform organisms. Polymyxin antibiotics are highly neurotoxic and nephrotoxic, and very poorly absorbed from the gastrointestinal tract. Polymyxins also have antifungal activity.
Well known examples:
- Colistin
- Polymyxin B
- Surfactin
Polymyxin acts as an antibiotic by damaging the cytoplasmic membrane of bacteria.
Also polymyxins biological source is Bacillius polymyxa.
Polymyxins are antibiotics, with a general structure consisting of a cyclic
peptide with a long hydrophobic tail. They disrupt the structure of the
bacterial cell membrane by interacting with its phospholipids. They are
produced by nonribosomal peptide synthetase systems in Gram-positive bacteria such as Paenibacillus polymyxa and are
selectively toxic for Gram-negative bacteria due to their specificity for
the lipopolysaccharide molecule that exists within many Gram-negative outer membranes.
Polymyxins B and E (also known as colistin) are used in the
treatment of Gram-negative bacterial infections. The global problem of advancing antimicrobial resistance has led to a renewed interest in their use recently.
Polymyxin M is also known as "mattacin".

# Mechanism of action
After binding to lipopolysaccharide (LPS) in the outer membrane of Gram-negative
bacteria, polymyxins disrupt both the outer and inner membranes. The hydrophobic
tail is important in causing membrane damage, suggesting a detergent-like
mode of action.
Removal of the hydrophobic tail of polymyxin B yields polymyxin nonapeptide,
which still binds to LPS but no longer kills the bacterial cell. However, it
still detectably increases the permeability of the bacterial cell wall to other
antibiotics, indicating that it still causes some degree of membrane
disorganization.
Gram-negative bacteria can develop resistance to polymyxins through various
modifications of the LPS structure that inhibit the binding of polymyxins to
LPS.

# Clinical use
Polymyxin antibiotics are relatively neurotoxic and nephrotoxic and are usually used only as a last resort if modern antibiotics are ineffective or are contraindicated. Typical uses are for infections caused by strains of multidrug-resistant Pseudomonas aeruginosa or carbapenemase-producing Enterobacteriaceae.
Polymyxins are not absorbed from the gastrointestinal tract, and, therefore, another route of administration must be chosen, e.g., parenteral (often intravenously) or by inhalation (unless perhaps
the target is bacteria in the gastrointestinal tract).
Polymyxins have less effect on Gram positive organisms, and are sometimes combined with other agents (as with Trimethoprim/polymyxin) to broaden the effective spectrum.

# Use in biomedical research
Polymyxins are used to neutralize or absorb LPS, which contaminates samples that are intended for use in, e.g., immunological experiments. Minimization of LPS contamination can be important because LPS can evoke strong reactions from immune cells and, therefore, distort experimental results.
By increasing permeability of the bacterial membrane system, polymyxin is also used in clinical work to increase release of secreted toxins, such as Shiga toxin from Escherichia coli.