Fumispore

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|2º TEXTO |

This group of drugs has often been classified as non-specific protoplasmic poisons and indeed such views are still expressed today. Such a broad generalisation is, however, very far from the true position.

It is convenient to consider the modes of action in terms of the drugs' targets within thebacterial cell and in the following pages various examples will be given. The targets to be considered are the cell wall, the cytoplasmic membrane and the cytoplasm. Much more detailed treatments of the subject will be found in the references at the end of this chapter.

- sobre la pared celular (fenol, formol, mertiolato)

The cell wall

This structure is the traditional target for a groupof antibiotics which include the penicillins but a little-noticed report which appeared in 1948 showed that low concentrations of disinfectant substances caused cell wall Iysis such that a normally turbid suspension of bacteria became clear. It was thought that these low concentrations of disinfectant cause enzymes whose normal role is to synthesis the cell wall to reverse their role in some wayand effect its disruption or Iysis.

In the original report, the disinfectants (at the following percentages: formalin,0,12; phenol, 0,32; mercuric chloride, 0,0008; sodium hypochlorite, 0,005 and merthiolate,0,0004) caused Iysis of E. coli, streptococci and staphylococci.

Glutaraldehyde also owes part of its mode of action to its ability to react with, and provide irreversible cross-linkingin, the cell wall. As a result, other cell functions are impaired. This phenomenon is especially found in Gram-positive cells.

- sobre membrana citoplasmática

The cytoplasmic membrane

Actions on the cytoplasmic membrane may be divided into three categories.

1 Action on membrane potentials.

2 Action on membrane enzymes.

3 Action on general membrane permeability.

- sobrepotenciales de membrana (salicilamidas)

Action on membrane potentials

Recent work has shown that bacteria, in common with chloroplasts and mitochondria, are able, through the membrane-bound electron transport chain aerobically or the membrane-bound adenosine triphosphatase anaerobically, to maintain a gradient of electrical potential and pH such that the interior of the bacterial cell is negativeand alkaline. This potential gradient and the electrical equivalent of the pH difference(1 pH unit = 58 mV at 37°C) give a potential difference across the membrane of100-180mV, with the inside negative. The membrane is impermeable to protons, whose extrusion creates the potential described.

These results may be expressed in the form of an equation, thus:

Dp = Dy - ZDpH

where Dp is theprotonmotive force, Dy the membrane electrical potential and DpH the trans-membrane pH gradient, i.e. the pH difference between inside and outside the cytoplasmic membrane. Z is a factor converting pH units to millivolts so that all the units of the equation are the same, i.e. millivolts. Z is temperature dependent and at 37°C has a value of 62.

This potential, or protonmotive force as it is alsocalled, in turn drives a number of energy-requiring functions which include the synthesis of adenosine triphosphate ,the coupling of oxidative processes to phosphorylation, a metabolic sequence called oxidative phosphorylation and the transport and concentration in the cell of metabolites such as sugárs and amino acids. This, in a few simple words, is the basis of the chemiosmotic theory linkingmetabolism to energy-requiring processes.

Certain chemical substances have been known for many years to uncouple oxidation from phosphorylation and to inhibit active transport and for this reason they are named uncoupling agents. They are believed to act by rendering the membrane permeable to protons hence short-circuiting the potential gradient or protonmotive force.

Some examples of...