Ammonia production by pathogenic bacteria

Abstract

THE discovery of glutamine as a growth factor for Streptococcus haemolyticus [MDlclwain et at. 1939] and the occurrence ofhydrolytic and synthetic glutaminase in those animal tissues, kidney and liver [Krebs, 1935] which contain the most active deaminases [Krebs,. 1933], suggested that glutamine might play a part in the metabolism of amino-acids by streptococci, possibly as a carrier of labile NH3. It was considered desirable .therefore to examine the deamination of amino-acids by the organism since no interest has been shown in this field, though a soluble protease has been extracted by Stevens & West [1922]. Foster [1921] showed that NH, was liberated coincidently with disappearance ofNH,-N during the period of most active growth on glucose-broth or glucose-serum-broth, though subsequently NH2-N reappeared without disappearance ofNH3. This was assumed to be due to continued proteolysis without fuirther utilization of amino-acids. Out of 101 substrates tested as H-donators to indigo-tetrasulphonate, 71, including theamino-acids,werefound by Farrell [1935] to be inactive. The present work reconciles these findings, since it is shown that out of 22 c-amino-acids only arginine yields significant amounts of NH.3 and the reaction is not oxidative but hydrolytic. As the same behaviour was shown by streptococci of diverse habitat and nutritional requirements, the study was extended to staphylococci. Minor differences were shown but arginine was quantitatively the most important source of NH3, urea, the next best, being not more than half as active. The observations of Fildes [1934] and Knight [1936] suggested that this restricted metabolic activity might be related to a habitat in association with the products of animal metabolism with the ultimate development of patho-genicity in many of the organisms examined. Comparative data for representative human and animal pathogens of other genera were lacking; early work on amino-acid breakdown was restricted to chemical identification of the products of putrefaction, often by mixed cultures of unidentified organisms, while the recent work of the Cambridge school, under better controlled conditions, has dealt almost entirely with strict anaerobes and Bacterium coli (for bibliography see Stephenson [1939]). Experiments on the meningococcus and the diphtheria and typhoid organisms were therefore carried out. The first two showed even more restricted chemical activity than the-gram-positive cocci previously examined and the last, though an active NH,3 producer, resembled Bact. coli, forming little NH3 from arginine. To find how far the breakdown of arginine was a constant character of gram-positive cocci, experiments were carried out with a strain of staphylococcus trained to grow on a synthetic medium with NH4+ salts as the main source of N [Gladstone, 1937, 2]. With such a strain.it is possible to alter at will any adaptive Whole-time worker for the Medical Research Council.