Albert Schatz

Streptomycin, a Substance Exhibiting Antibiotic Activity Against Gram-Positive and Gram-Negative Bacteria.∗†:

Summary A new antibacterial substance, designated as streptomycin, was isolated from two strains of an actinomyces related to an organism described as Actinomyces griseus. This substance resembles streptothricin in its solubility in water, mode of isolation and concentration from culture medium, its selective activity against gram-negative bacteria, and its limited toxicity to animals. However, the two substances differ in the nature of their respective bacteriostatic spectra as well as in their quantitative action upon different bacteria. It is suggested that one is dealing here with two closely related chemical compounds.

Effect of Streptomycin and Other Antibiotic Substances upon Mycobacterium tuberculosis and Related Organisms.

Summary Mycobacterium tuberculosis is subject to the bacteriostatic action of a variety of antibiotic substances. There is considerable variation in this respect, both in the sensitivity of the same organism to different substances and of different species or even strains of the same species of Mycobacterium to the same substance. Streptomycin is also highly effective against various related organisms, namely, Erysipdothrix and actinomy-cetes, comprising both saprophytic and parasitic strains, with considerable variation among different species.

Streptomycin-Induced Chlorophyll-less Races of Euglena

Summary When acted upon by streptomycin, certain strains of Euglena gracilis undergo a permanent loss of chlorophyll, without being inhibited in growth if good energy and carbon sources are supplied to make up for the loss of photosynthesis. The degree of exposure to streptomycin. Proliferating and non-proliferating cells, and cells exposd in the light and in the dark, appear equally susceptible to bleaching.

PRODUCTION OF ANTIBIOTIC SUBSTANCES BY ACTINOMYCETES

It has now been definitely established that a considerable proportion of all actinomycetes that can be isolated from soils or other natural substrates have the capacity of inhibiting the growth of, and even of destroying, bacteria and other microorganism.5 This was brought out emphatically in several of the surveys that have been made on the distribution of antagonistic properties among actinomycetes.1, 2, 4, 6, 10 Twenty to 50 per cent of all the cultures tested, whether freshly isolated from natural substrates or taken from culture collections, were found to possess antagonistic properties. The selective antimicrobial activities of actinomycetes differ greatly, both quantitatively and qualitatively, as could easily be demonstrated by their respective antibiotic spectra. The nature of the active agents or the antibiotics produced by these organisms depends upon the species; frequently upon the strain; the composition of the medium in which it is grown, and the conditions of cultivation.7, 8 Several distinct antibiotics have now been isolated from cultures of actinomycetes. Some, namely, actinomycetin, micromonosporin, mycetin, and actinomyces lysozyme, have been only partly purified, whereas others, including actinomycin, proactinomycin, streptothricin, and streptomycin, have been isolated and crystallized. These substances differ greatly in their chemical structure, antimicrobial properties, toxicity to animals, and in vivo activity. Some of the antibiotics are produced in simple synthetic media; others are formed in complex organic substrates; still others, like streptomycin, require the presence in the medium of a specific nutritive substance, an “activity factor,” which is either a precursor or a prosthetic group of an enzyme system essential for the production of the antibiotic agent. Although this “activity factor” can be synthesized by Streptomyces griseus, its addition to the medium favors the rapid production of streptomycin. Streptomyces griseus can, therefore, grow

Grisein, a New Antibiotic Produced by a Strain of Streptomyces griseus

Summary Streptomyces griseus is widely distributed in soils, peats and in composts. Only very few strains of this organism are capable of producing streptomycin. Most of the strains produce no antibiotic at all, whereas certain strains produce antibiotics that are distinctly different from streptomycin. One such new antibiotic was isolated and designated as grisein. Grisein is active against certain Gram-positive and Gram-negative bacteria. Its antibacterial spectrum is much more limited than that of either streptomycin or streptothriciiu Cultures of bacteria that are made resistant, by serial passage, to streptomycin still remain sensitive to grisein. Cultures of bacteria originally sensitive to grisein give rise easily to strains resistant to this antibiotic. Grisein shows a rather low toxicity to experimental animals and is rapidly excreted in the urine. It was found capable of protecting experimental animals against infections with S. schottmulleri and S. aureus.‡

Experimental In Vitro Demyelination

‘‘h CONSIDERING the pathology of multiple sclerosis, or indeed of any of the degenerative diseases of the nervous system, the mechanism of demyelination is one of the outstanding problems with which we are faced.”’ “For obvious reasons, the chemistry of the myelin destruction that accompanies Wallerian degeneration has been studied more intensively than that of other types of demyelination.”* In this process, physical destruction of myelin sheaths is the predominant feature during the first eight days following sectioning, whereas chemical degradation occurs from the eighth to the thirty-second day.* Wallerian degeneration is, therefore, relatively slow compared to the demyelination accomplished overnight by certain soil microflora.3 Such organisms would appear to be useful biologic reagents with which to investigate the chemistry of myelin degradation. This paper is concerned with applications of microbiology to the study of demyelinative phenomena. Previous investigations revealed that 132 soil microflora catabolized various lipids and lipid derivatives4 However, only six actinomycetes, out of the total 132 organisms surveyed, were found to markedly demyelinate blocks of bovine spinal cord in vitro.3 Because of this ability, these active cultures are now being exploited to develop in vitro demyelinating tests for screening chemical compounds to select agents with antidemyelinating properties. Substances effective in vitro may justify clinical trials to determine whether they interfere with demyelination in vivo. Such blocking agents may, in addition, help elucidate biochemical pathways whereby myelin is degraded. Finally, the active actinomycetes may provide enzymes and other myelinolytic substances that can be used to take myelin apart in a piecemeal manner, and thus contribute information concerning the physicochemical structure of this complex material. The present work was undertaken to study strain variation and conditions for maximal production of myelinolytic agent(s) by Streptomyces grbeus, the most active species so far obtained.

Soil, Water, Food, and Teeth

“Perhaps if we forgot about dental caries for a while and just became curious about teeth and their environment we might accumulate sufficient knowledge to answer many questions.”

Biochemical Studies with Mixed Populations of Oral Bacteria

UMEROUS quantitative investigations have attempted to determine qualitatively which organisms are the causative agents of dental caries and how enamel is destroyed. Examples of such work are pH measurements of saliva, plaque material, and pure and impure cultures of oral microflora, as well as the classical plate counts for total bacteria, acid formers, and other groups. Much of this voluminous literature has been competently surveyed in 1952 and is now conveniently accessible.1 However, the constantly changing interrelationships between the mixed microfloral population as a whole and its mean, over-all, or statistical biochemistry have received much less attention. Yet this kind of dynamic approach is suggested by the variability of conditions in the mouth. While some properties (e.g., moisture and temperature) remain fairly constant, others (e.g., diet and pH) vary continuously or discontinuously. These changes may be cyclical (e.g., variation in oxidation-reduction potential) and may result from factors intimately interrelated and exerting a mutual influence upon one another. For example, bacterial action is largely responsible for the pH of the microbic milieu while pH in turn exerts a selective, directive, or otherwise controlling effect on the biochemical activities of the developing culture. Direct qualitative studies of this kind of mass population dynamics would be different from the more static and quantitative technics so far largely employed. This paper reports experiments on the cultural properties and respiratory activities of mixed populations representing different physiologic groups of oral microorganisms. The objective was more to explore the respirometric methodology for studying the metabolism of oral bacteria in mixed culture than to conduct a comprehensive biochemical investigation. Although the Warburg technic has already been used to measure oxygen consumption by salivary microflora,2-4 its general usefulness exceeds this particular purpose.

The Importance of Chelation in Composting: A Historical Perspective

▪ Much more research is presently being done on composting organic wastes than on humification in the soil. Humus research has therefore been reincarnated in the form of composting research. However, chelation is a neglected but important chemical reaction in composting and the utilization of compost as a soil amendment, just as it has been in soil formation and soil fertility. Research is needed to clarify the role of chelation in composting. It is also important to recognize the limitations in interpreting results from compost research in which the role of chelation was not considered.

Metabolism of Esters by Streptomyces nitrificans.

Summary A homogenate of urethan-grown S. nitrificans exhibited a marked increase in oxygen uptake when supplied with many esters. Carbamates generally exerted a lesser though significant stimulation of gas consumption. Growth on urethan therefore produced cell material containing esterase(s) characterized by broad spectrum activity. But whether carbamates are hydrolyzed by these or specific enzymes is not yet known. Acetylcholine showed the least activity of all substrates tested, although choline caused an appreciable increase in oxygen uptake.