Guy P. Youmans

Effect of Streptomycin on Experimental Infections Produced in Mice with Streptomycin Resistant Strains of M. tuberculosis var. Hominis

Summary Streptomycin resistant human type tubercle bacilli were found to be as virulent for white mice as streptomycin sensitive strains. Infection produced in mice with these streptomycin resistant cultures was not suppressed by treatment of the mice with streptomycin.

The in vitro inhibition of growth of intracellular Listeria monocytogenes by lymphocyte products

Abstract The listeria-inhibiting activity of culture supernatants from listeria-immune and nonimmune lymphocytes was assessed on listeria-infected macrophage cultures. It was found that supernatant from listeria-immune lymphocyte cultures stimulated in vitro with antigen was markedly inhibitory to the multiplication of intracellular listeria. Some inhibitory activity was also evident in supernatant from antigen-stimulated non-immune lymphocyte cultures. Supernatant from listeria-immune lymphocytes stimulated in vivo with antigen was capable of inhibiting listeria. Some inhibitory activity was still evident upon dilution of active supernatant at 1:100.

The use of the mouse for the testing of chemotherapeutic agents against Mycobacterium tuberculosis.

During the last few years, increasing use has been made of iri t ravenously infectetl mice for the determination of the ability of substances to suppress experimental tul~erciilosis.-l! The use of mice for this 1)urpose is favored by the foliowiiig factors: an acute experiment o f 3 t:) 4 weeks duration can be easily performctl; the intravenous route of inoculation by-passes intermediate barriers and delivers a nearly uniform dosage to the lungs; the variables of environment are readily controlled; the variables of allergy and induced resistance are probahly minimized; statistically significant numbers of mice are more easily maintained than is the case with larger animals; smaller amounts of drug are required; the histopathology has been studietl and defined so the evaluation of results now may be more easily made. Furthermore, comparative studies have shown that the sulfonamities, sulfones, para-aminosalicylic x i t l , and streptomycin, substances which su1)press experimental tulierculosis of guinea pigs, also have a similar action in mice, although the degree of su1q)ression of the disease i n mice is frequently less marked than in guinea pigs.

Production of Small Colony Variants of Staphylococcus aureus by the Action of Penicillin.

Summary Unstable small colony variants were readily produced from nine out of ten strains of Staphylococcus aureus upon exposure to penicillin.

Production of Small-Colony Variants of Staphylococcus aureus.

We have previously reported the production of small-colony variants, or G forms, after prolonged serial transfer of S. aureus in lithium chloride broth or plain broth media. 1 , 2 Swingle 3 subsequently confirmed these results and also obtained these forms after extended growth in nutrient broth or casein-digest medium. Under these conditions the variants occur only rarely and in small numbers, seldom exceeding 1.0% of the colonies on a plate. Chinn 4 in a study of the metabolic activity of the small colony variants of S. paradysenterió Sonne and S. aureus found them to be metabolically far less active than the normal forms, having a reduced generation-time, reduced fermentative powers, lessened ability to reduce methylene blue and a slower cataphoretic velocity. This lowered metabolic activity and the ability to revert to forms identical with the parent culture furnishes some evidence that small-colony variants may be forms whose metabolism has been greatly reduced by some unknown factor. Quastel and Woolridge 5 studying the enzymes of B. coli found that among many inorganic salts barium, chloride was the most effective in inhibiting the metabolic activity of washed suspensions of these organisms. These results, and the known lowered metabolic activity of the small-colony variants, indicated that barium chloride might be effective as an incitant of their production. Concentrations of barium chloride of 0.5 to 5.0% were made up accurately in 1.0% peptone solution. Since S. aureus produces only slight growth in plain peptone medium the acetone-soluble portion of meat extract containing Hughes 6 growth factor was added. This was prepared by extracting 50 gm. of meat extract dissolved in 100 cc. distilled water with 6 to 8 volumes of acetone.

Occurrence of Streptomycin Resistant Tubercle Bacilli in Mice Treated with Streptomycin.

Summary Streptomycin resistant tubercle bacilli were obtained from the majority of intravenously tubercularized mice treated with amounts of streptomycin which permitted a relatively loag survival time.

Streptomycin Resistant Variants obtained from Recently Isolated Cultures of Tubercle Bacilli.

Conclusion Streptomycin resistant variants were obtained from 25 out of 57 (43.5%) recently isolated strains of tubercle bacilli.

Subsurface Growth of Virulent Human Tubercle Bacilli in a Synthetic Medium.

Summary Suspensions of five virulent strains of My. tuberculosis var. hominis were found to rapidly produce subsurface growth when inoculated into synthetic medium. One avirulent rapidly growing strain grew in a similar manner.

Effect of the h37ra strain of m. Tuberculosis and of a mycobacterial rna fraction on tumor growth.

Summary Data are presented to show that both an H37Ra strain of Mycobacterium tuberculosis and a ribosomal RNA fraction from this strain are effective inhibitors of tumor growth in mice. Mice were pretreated with tubercle bacilli or RNA fraction and challenged 5 weeks later with mixtures of tumor cells and the respective pretreatment agents. Comparative data with BCG are presented. Inhibition did not appear to be due to any direct toxic effect of tubercle bacilli or ribosomal RNA fraction on tumor cells. The necessity, for an inhibitory effect, of tuberculin hypersensitivity was deemed unlikely because the ribosomal RNA fraction neither induces nor provokes tuberculin hypersensitivity. The inhibition realized with mycobacterial extract avoids the risk to the tumor-bearer of viable organisms.

An Improved Method for Testing of Bacteriostatic Agents Using Virulent Human Type Tubercle Bacilli.

Summary A new technic for rapidly and efficiently testing the growth-inhibiting action of substances on virulent human type tubercle bacilli is described. The order of effectiveness of four compounds in inhibiting the growth of the avirulent acid-fast rapidly growing organism 607 was found to be: Sulfathiazole, sulfadiazine, 4,4diaminodiphenylsulfone, and sulfanilamide, while for the virulent human strain of tubercle bacillus H37Rv the order was found to be: 4,4diaminodiphenylsulfone, sulfathiazole, sulfadiazine, and sulfanilamide.