Miracle molecules of our age: ethylenediaminetetraacetic acid.

Abstract

In his outstanding book, Power Aging (1), Gary Null spends much of the early part of the volume discussing the numerous man-made chemicals and components that constitute a major part of the problems with pollution and damage to human health. It is almost as though anything chemical which we manufacture and use in our world can damage us. Even the pharmaceuticals which have been designed and synthesised, especially to cure us, always have side-effects some of which appear to be at least as bad as the conditions that they were designed to abolish. In view of what Dr Null says, can we find any synthetic chemicals which are harmless to man and yet have useful and important health benefits for which they were not designed? Here I discuss one agent, namely ethylenediaminetetraacetic acid (EDTA) that seems, at present, to fit the above criteria. 1. EDTA as a bacterial permeabiliser It is as a permeabiliser, particularly of Gram-negative bacteria, that EDTA is best known. Numerous inhibitory agents are hydrophobic, and because these fail to enter Gram-negative organisms, they cannot kill them nor even inhibit their growth Le. they cannot have a bactericidal nor a bacteriostatic effect Generally, failure of hydrophobic agents to penetrate into the Gram-negative cell results from the outer membranes (OMs) being impenetrable to them, hence preventing their passage across the envelope (2,3). Outer membrane impenetrability as the basis of the above effects can be proven, for hydrophobic agents, by comparing their effects on normal strains and those (lps mutants) altered in the lipopolysaccharide (LPS) component of the OM; whereas unmutated strains are insensitive to hydrophobic agents, they readily cross the envelopes of the mutants with a lethal effect (2,3). Strikingly, the OMs of some Gram-negative bacteria can also be permeabilised by treatment with EDTA. This molecule is a chelator and its removal, by chelation, of magnesium, manganese and calcium ions from the OMs leads to permeabilisation. These ions are intimately involved in the LPS-LPS and LPS-protein interactions which stabilise the OMs, and so removal of them leads to loss of LPS from the envelopes and permeabilisation to the normally non-penetrating hydrophobic agents (2-4). The removal of these ions and the loss of LPS from the OMs, in the presence of EDTA, is particularly marked in pseudomonads, so that these organisms show the most marked sensitisation by EDTA (3,4). Hydrophilic antibacterials normally cross the OMs via the porins, provided that these antibacterials are less than ca 600 molecular weight (2). If this is so, then Gram-negatives show sensitivity to them in the absence of EDTA. Many such agents will, however, also show an increased effect on EDTA-treated organisms, as the hydrophilic molecules will use both entry routes i.e. entering via both the porins and the permeabilised OMs. Hydrophilic antibacterials above 600 molecular weight normally fail to affect Gram-negatives; after permeabilisation by EDTA, however, some of them will use the OM route and cause lethality (2). As a result of its permeabilising effect, EDTA generally sensitises Gram-negatives to an array of potentially lethal agents to which they are inherently resistant. Such agents can be divided into four classes namely disinfectants, antiseptics, preservatives and antibiotics (4). Many of these agents are hydrophobic, and therefore, cannot enter Gram-negatives, especially pseudomonads, without permeabilisation. The permeabilising effect of chelators such as EDTA is especially important for antiseptics and antibiotics, because organisms are more and more commonly becoming resistant to such agents that originally killed them. The ability of chelators such as EDTA to reverse this effect is of great importance. EDTA and enhanced lethal effects of disinfectants, antiseptics and antibiotics on organisms on inert surfaces, on wounds and on burns Because phenols and cresols are hydrophobic, they generally fail to kill Gram-negatives and therefore cannot be used to disinfect inert surfaces. …