Antimicrobial activity of n-alkyltrimethylammonium bromides: influence of specific growth rate and nutrient limitation.

The antimicrobial activity of an homologous series of n-alkyltrimethylammonium bromides has been assessed towards Escherichia coli grown at a variety of specific growth rates and under various conditions of nutrient limitation. For each individual set of growth conditions activity was parabolically related to the n-alkyl chain length of the compounds and thus to compound lipophilicity (log P). The compound that showed optimal activity and thereby optimal lipophilicity (log Po) changed according to growth rate and nutrient limitation. Such changes are related to variations in the gross cell envelope composition of the cultures (phospholipid, lipopolysaccharide, neutral lipids, proteins). The data therefore support the hypothesis that changes in growth rate and nutrient limitation alter the overall lipophilicity of the cell envelope and thereby the optimal value of log P for compounds to traverse it. Additionally, the data suggest that for the compounds examined, the neutral acidic:neutral phospholipid ratios of the cell envelope, also influence the permeation of it.

Influence of specific growth rate and nutrient-limitation upon the sensitivity of Escherichia coli towards polymyxin B.

The sensitivity of Escherichia coli to the lytic action of polymyxin B was assessed for cells grown in a chemostat at a variety of specific growth rates and under conditions of carbon, nitrogen, phosphorus and magnesium limitation. Magnesium and phosphorus limited cells demonstrated a trend of increased resistance with increasing growth-rate, whereas carbon and nitrogen limited cells increased their sensitivity as the growth rate increased. Divergent patterns of sensitivity, such as these, allowed a number of models for resistance towards polymyxin to be assessed. It was not possible to attribute polymyxin sensitivity to any single envelope component; rather the patterns of sensitivity reflect, in a complex manner, presence of envelope proteins and acidic phospholipids.

Influence of specific growth rate and nutrient limitation upon the sensitivity of Escherichia coli towards chlorhexidine diacetate.

The sensitivity of Escherichia coli to chlorhexidine has been assessed for cells grown in a chemostat at a variety of specific growth rates, under conditions of carbon, nitrogen, phosphorus and magnesium limitation. At slow rates of growth (ca 0.08/h) little difference in sensitivity was observed. As growth rate was increased, however, the sensitivity of nitrogen- and carbon-limited cells increased whilst that of magnesium- and phosphate-limited cells decreased. It was not possible to correlate the observed patterns of chlorhexidine sensitivity with any single measure of cell envelope composition (phospholipid content, lipopolysaccharide, envelope proteins, etc.). The results presented are not consistent, therefore, with any simple model for chlorhexidine binding or action and more probably reflect subtle interaction between chlorhexidine, phospholipid-lipopolysaccharide complexes and cations within the envelope.

The effect of vasovasostomy upon the structure of the vas deferens in rats.

The reasons for the discrepancy between reappearance of sperm in the ejaculate following vasovasostomy and pregnancy rates remain obscure. To determine the possible adverse effects of reanastomosis upon the structure of the vas deferens, immediate microsurgical vasovasostomy was performed on 60 adult Sprague-Dawley rats. The fine structure of the mucosa, as seen by scanning electron microscopy, showed only subtle, transient changes with return to normal architecture within 3 months. Luminal dilatation, rather than stenosis, was a constant late finding. It is concluded that microsurgical reanastomosis has little, if any, permanent deleterious effect upon the structure of the vas deferens.