Polymyxins are antibiotic

Antibiotic

An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...

s, with a general structure consisting of a cyclic
peptide

Peptide

Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...

 with a long hydrophobic tail. They disrupt the structure of the
bacterial cell membrane by interacting with its phospholipid

Phospholipid

Phospholipids are a class of lipids that are a major component of all cell membranes as they can form lipid bilayers. Most phospholipids contain a diglyceride, a phosphate group, and a simple organic molecule such as choline; one exception to this rule is sphingomyelin, which is derived from...

s. They are
produced by the Gram-positive bacterium Bacillus polymyxa and are
selectively toxic for Gram-negative bacteria due to their specificity for
the lipopolysaccharide

Lipopolysaccharide

Lipopolysaccharides , also known as lipoglycans, are large molecules consisting of a lipid and a polysaccharide joined by a covalent bond; they are found in the outer membrane of Gram-negative bacteria, act as endotoxins and elicit strong immune responses in animals.-Functions:LPS is the major...

 molecule that exists within many Gram-negative outer membranes.

Polymyxins B

Polymyxin B

Polymyxin B is an antibiotic primarily used for resistant gram-negative infections. It is derived from the bacterium Bacillus polymyxa. Polymyxin B is a mixture of two closely related compounds, polymyxin B1 and polymyxin B2. It has a bactericidal action against almost all gram-negative bacilli...

 and E (also known as colistin

Colistin

Colistin is a polymyxin antibiotic produced by certain strains of Bacillus polymyxa var. colistinus. Colistin is a mixture of cyclic polypeptides colistin A and B. Colistin is effective against most Gram-negative bacilli and is used as a lingerdoodle. It is one of the last-resort antibiotics for...

) 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

Detergent

A detergent is a surfactant or a mixture of surfactants with "cleaning properties in dilute solutions." In common usage, "detergent" refers to alkylbenzenesulfonates, a family of compounds that are similar to soap but are less affected by hard water...

-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

Pseudomonas aeruginosa

Pseudomonas aeruginosa is a common bacterium that can cause disease in animals, including humans. It is found in soil, water, skin flora, and most man-made environments throughout the world. It thrives not only in normal atmospheres, but also in hypoxic atmospheres, and has, thus, colonized many...

or carbapenemase-producing Enterobacteriaceae

Enterobacteriaceae

The Enterobacteriaceae is a large family of bacteria that includes many of the more familiar pathogens, such as Salmonella, Escherichia coli, Yersinia pestis, Klebsiella and Shigella. This family is the only representative in the order Enterobacteriales of the class Gammaproteobacteria in the...

.

Polymyxins are not absorbed from the gastrointestinal tract, and, therefore, another route of administration

Route of administration

A route of administration in pharmacology and toxicology is the path by which a drug, fluid, poison, or other substance is taken into the body.-Classification:Routes of administration are usually classified by application location...

 must be chosen, e.g., parenteral (often intravenously) or by inhalation.

Polymyxins have less effect on Gram positive organisms, and are sometimes combined with other agents (as with Trimethoprim/polymyxin

Trimethoprim/polymyxin

The drug combination trimethoprim/polymyxin is an antimicrobial solution for topical ophthalmic use in the treatment of acute bacterial conjunctivitis and blepharoconjunctivitis....

) to broaden the effective spectrum.

Use in biomedical research

Polymyxins are used to neutralize or absorb LPS-contaminating 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.