Hi listers,
Here is the Chap. 22 info referred to in Pt 1.
Fundamentals of control
Mode of action
The many processes and substances which function as antimicrobial
agents manifest their activity in one of several ways. For academic and
practical reasons, it is important to have some concept of how
microorganisms are inhibited or killed. Knowledge of the mode of action
of a particular agent may make it possible to predict the conditions
under which it will function most effectively as well as its
antimicrobial spectrum. A great deal of research has been performed to
determine the specific site of action of various agents. Such
investigations are complicated by the fact that when a cell is exposed
to a lethal agent many changes can be observed. The real problem is to
establish the initial damage by the agent which is responsible for the
general deterioration of the vital precesses.
In a general way, one may view the possible sites of action of an
antimicrobial agent by recalling certain features of the microbial cell.
A normal living cell contains the multitude of enzymes responsible for
metabolic processes. A semipermeable membrane (cytoplasmic membrane)
maintains the integrity of the cellular contents; the membrane controls
the passage of substances between the cell and its external environment
and is also the site of some enzyme reactions. The cell membrane proper
provides a protective covering to the cell in addition to participating
in certain physiological processes. Damage at any one of these levels
may initiate the changes leading to the death of the cell. The possible
sites of damage and agents responsible for the damage are several.
Damage to cell wall (membrane)
The cell membranes of some gram-positive bacteria are attacked by the
enzyme lysozyme found in tears,leucoytes, mucous secretions, and other
natural sources. Enzymes produced by several bacterial species are
capable of degrading the cell membrane structure of other species. Dis
integration of the cell membrane is followed by lysis. Some agents may
inhibit the formation of cell membrane material in a growing bacterial
culture, with the resulting formation of protoplasts. The protoplast
structure is susceptible to lysis unless special conditions are
provided. The antimicrobial effect of penicillin is attributed to its
inhibition of cell membrane synthesis.
Alteration of cell permeability
The cytoplasmic membrane preserves the integrity of the cellular
constituents as well as the selective transport of nutrients into the
cell. Damage to this membrane may result in the inhibition of growth or
the death of the cell. The antimicrobial activity of phenolic compounds,
synthetic detergents,soaps, and quaternary ammonium compounds is
attributable to their effect on cell permeability. These substances
destroy the selective permeability of the membrane, permitting leakage
of cellular constituents. This can be demonstrated experimentally by
suspending bacterial cells in an aqueous phenol solution and then, at
intervals, analyzing for nitrogen and phosphorus in samples of the cell
-free fluid. the bactericidal action of these agents can be correlated
with the leakage of nitrogen and phosphorus from the cell.
Alteration of protein molecules
The viability of a cell is associated with maintenance of protein
molecules in their natural state. A condition or substance which alters
this state, i.e., denatures the proteins,may irreparably damage the
cell. High temperatures denature proteins. Similarly, appropriate
concentrations of alcohol will denature proteins, producing a lethal
effect.
Inhibition of enzyme action
Each of the hundreds of different enzymes in the cell is a potential
target for an inhibitor. Inhibition of the energy-supplying reactions
may be particularly deterimental; many agents affect enzymes in these
key pathways, e.g., the glycolytic system, the Krebs tricarboxylic acid
cycle, and the cytochrome system. For example, cyanide inhibits
cytochrome oxidase, fluoride inhibits glycolysis, and trivalent arsenic
compounds block the tricarboxylic acid cycle. Dinitrophenol uncouples
oxidative phosphorylations.
Strong oxidizing agents,e.g., halogens and hydrogen peroxide,may damage
cellular constituents to such an extent that they can no longer perform
normal metabolic functions. For example, the activity of many enzymes
depends upon one of their components, a sulfhydryl group,-SH. An
oxidizing agent may alter this chemical arrangement and inactivate the
enzymes.
Inactivation of certain enzymes may come about as a result of
combination with metallic ions as mercury or silver. Note that the
effect is upon the sulfhydryl group. There are some instances of
inhibition in which the initial "lesion" is an interference in a
specific biosynthesis. A classical example is the blockage of folic acid
synthesis by sulfanilamide. One of the components of the folic acid
molecule is p-aminobenzoic acid,whose chemical structure is very similar
to that of sulanilamide. The sulfanilamide competes with the
p-aminobenzoic acid for the enzyme surface, thereby preventing synthesis
of the essential folic acid. Many other synthetic processes can be
interrupted by making available a compound structurally related to, but
slightly different from the natural metabolite ( silver ions attach to
and slightly alter metabolite structures). Some antibiotics function as
competitive inhibitors of essential synthetic processes by acting as
partial or total metabolic analogs. Examples are
chloramphenicol,oxamycin, and penicillin.
A posting on enzymes and catalysts is forthcoming.
Bless you Bob Lee
--
oozing on the muggy shore of the gulf coast
[email protected]
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