The Action of Urea and Some of its Derivatives on Bacteria
Authors: Weinstein Louis , McDonald Alice 
Published: January 2023

Summary and Conclusions
Studies of the action of two carbamates on various bacteria revealed that a 2 to 3 per cent concentration of urethane was bacteriostatic for all of the gram-negative organisms investigated, and that their susceptibility to urea was much less, since at least 6 per cent of this drug was required to accomplish the same degree of bacteriostatic effect with some of the organisms. E. typhi, S. paradysenteriae, S. schottmülleri, and Ps. aëruginosa, E. coli, and Streptococcus pyogenes, were most susceptible to the action of urethane while Diplococcus pneumoniae and Proteus vulgaris were inhibited to a somewhat lesser degree. P. vulgaris, Streptococcus pyogenes, and Ps. aëruginosa were the organisms least affected by urea. Most resistant to the action of the carbamates was Staphylococcus aurus.
Tests of the bactericidal activity of the carbamate compounds showed that, in a concentration of 10 per cent, urethane was regularly bactericidal for all of the gram-negative bacteria investigated. Staphylococcus aureus was also killed by this concentration of drug but a longer period of time was required than for the other organisms. The lethal effect occurred in from 5 to 15 minutes of exposure with the most susceptible bacteria. With some strains, a 5 per cent solution of urethane was found to produce death although the time required for killing was prolonged. Urea was found to be considerably less potent than ethyl carbamate in destroying the viability of bacterial cells since a concentration of 20 per cent of this substance required a much longer time to kill than 10 per cent urethane. Mixtures of quantities of the two drugs which separately exerted little antibacterial effect were found to be highly bacteriostatic when combined. It was impossible to ascertain whether or not this effect was additive or the result of potentiation of one substance by the other.
Investigations of the activity of the carbamates in different media revealed that the addition of organic material, in the form of horse-serum, not only did not reduce their antibacterial effects but, in many instances, actually increased them. The results obtained in synthetic media were difficult to compare with those in veal-infusion broth with or without added horse-serum because a large inoculum of organisms had to be used to start growth. It seemed, however, that the effect of urea and urethane in synthetic broth probably was more marked than in media of poorly-defined composition.
Studies of the effect of both carbamate compounds on the growth-curve of E. coli revealed that, even with concentrations which did not produce notable bacteriostasis when observed only at the end of the 24 hours, there was early inhibition of growth characterized mainly by prolongation of the lag-phase for varying periods of time, depending on the strength of the drug. The death-phase was found to follow immediately after the lag-period if the amount of urethane employed was large enough.
The exact mode of action of urea and urethane on bacteria could not be determined. The effect of these compounds in producing changes in hydrogen-ion concentration and osmotic pressure was studied and the data obtained indicated that neither of these factors probably played a role in the production of the antibacterial phenomenon. It has been pointed out by Harvey and others that urethane, in proper concentration, inhibits the enzymes responsible for respiration and luminescence in the luminescent group of bacteria. If an analogy can be drawn between this group of organisms and the ones reported in this paper, the possibility exists that the antibacterial effects noted in the present study resulted from inhibition of some essential enzymic systems of the bacteria. A direct study of the influence of urea and ethyl carbamate on the enzymic activity of the organisms which are adversely affected by these substances is necessary to prove this possible mechanism of action of the carbamates.