Many hypotheses explaining the channel formation induced by gramicidin A have
been put forth over the years. For example, two molecules of gramicidin form a “head-to-
head” helix, spanning the total width of the cell membrane. The helix creates a pore lined
with hydrophilic groups, permitting ion transport across the otherwise impermeable
lipid barrier of the membrane. Such a pore can accommodate even large ions, as long
as they are dehydrated. The movement of ions in the pore has been simulated in silico,
using elaborate molecular modeling calculations.
Colicins, bacteriostatic peptides encoded by bacterial plasmids, have been crystal-
lized and investigated by X-ray crystallographic methods. They have a mass of 79,000
daltons and an axial ratio of 1:10, giving these peptides a length of about 20 nm. They
are capable of forming a transmembrane channel with a diameter so large that glucose
molecules can pass through. Of course, this fatally disrupts the membrane potential of
the bacterial cell, with consequent bacteriostatic activity.
Ionophoric antibiotics do not distinguish microbial from mammalian membranes and
are therefore therapeutically limited. However, they are excellent tools for studying
membrane transport phenomena.
9.4.2.1 Surface-Active Antibacterial Agents
Biological membranes are indispensable to the proper functioning of all cells, includ-
ing bacteria and fungi. Hence, any agent that disrupts the membrane or otherwise inter-
feres with its integrity or function is a potential threat to the life of the cell.
Aliphatic alcohols are bactericidal because they damage the bacterial membrane, result-
ing in a rapid loss of the cytoplasmic constituents of the bacterium. At high concentrations,
such alcohols cause lysis (dissolution) of the bacterial cell. Because they damage bacterial
membranes, phenol (9.58) and cresol (9.59) are also effective disinfectants and are used in
commercial preparations (e.g., Lysol). They not only denature proteins but also act as
detergents, owing to the polarity of the phenolic hydroxyl group. The activity of phenols
can be increased considerably by attaching an alkyl side chain to the benzene ring, as in
n-hexylresorcinol (9.60), which makes the resulting compound more surface active.
Hexachlorophene (9.61) and fentichlor (9.62) are also very active and are used in disinfectant
EXOGENOUS PATHOGENS AND TOXINS 571