Comparison of antibacterial and antiimmune effects of certain rifamycins

Abstract

Comparison of the in vivo and in vitro immunosuppressive activities of the five rifamycins with their in vitro antibacterial and anti-ribonucleic acid polymerase activities indicated that correlation was poor. Examination of their activities on mitogen-induced blastogenesis in human peripheral blood leukocytes and inhibition of delayed-type hypersensitivity to partially purified protein derivative in immunized mice demonstrated that correlation was usually good. Antibacterial activity in cultures and the activities of the rifamycins inhibiting deoxyribonucleic acid-dependent ribonucleic acid polymerase appeared to correlate well. However, when these two types of activity, antiimmune and antibacterial, were compared, correlation was poor on occasion and indicated that the antiimmune activities and antibacterial activities of the rifamycins are probably not related.It has been reported previously (6) that some members of the ansamycin class of antibiotics, including certain rifamycins and streptovaricins, share the well-recognized immunosuppressive properties of rifampin (3,4,8,11). It was noted in that report that when the in vitro antibacterial activity of these substances was compared with their in vivo immunosuppressive activity, correlation was poor, suggesting that the two activities are unrelated.The following is a report of studies of the immunosuppressant activity of five rifamycins, chosen because they had large differences in antibacterial activity. Comparison of the antibacterial and immunosuppressant activities of these compounds demonstrated that their in vitro antimicrobial activity was often unrelated to their in vivo and in vitro immunosuppressive effects.MATERIALS AND METHODS Rifamycins used. The following rifamycins were kindly supplied by Gruppo Lepetit, Milano, Italy (the minimal inhibitory concentrations required for Mycobacterium tuberculosis, as determined in Lepetit's laboratory, are within parentheses): rifampin (0.5 ug/ ml), rifamycin SV (0.05 Ag/ml), rifamide (0.2 ytg/ml), 8 methyl-rifamycin (5 tLg/ml), and rifamycin formo-S (5 jg/ml). (See Results.) Rifamycins were prepared for use by dissolving them in a minimal volume of a 1:10 mixture of dimethyl sulfoxide (Me2SO) (Mallinckrodt, St. Louis, Mo.) and fetal calf serum (Grand Island Biological Co., Grand Island, N.Y.). This solution was further diluted with a volume of physiological saline sufficient to provide the desired concentration of drug. Solutions used for control studies contained a concentration of Me2SO and fetal calf serum in saline equal to the drugcontaining solutions.Inhibition of in vitro blastogenesis. The effects of the rifamycins studied on mitogen-induced blastogenesis were assayed by using human peripheral blood leukocytes. Blood was drawn from healthy donors into heparinized tubes, and the leukocytes were isolated and cultured by the method of Thompson et al. (14) and by the microculture technique with 5 x 104 cells in 0.2 ml of Eagle medium supplemented with pooled human AB plasma, penicillin, streptomycin, an...

Hygrocins A and B, Naphthoquinone Macrolides from Streptomyces hygroscopicus

“…For example, streptovaricins and rifamycins have a bridge chain of 17 carbons, and naphthomycins have a bridge chain of 23 carbons. Hygrocins A and B are the ansamycins with the shortest bridge ring (13 carbons) thus far isolated, which might account for their much weaker biological activity as compared with the above-mentioned known ansamycins (Table ) 4 Antimicrobial Activity of Hygrocin A and Hygrocin B in Comparison to Rifamycin S MIC (μg/mL)organismhygrocin A 12a hygrocin B 12a rifamycin S 12b,c Staphylococcus aureus 2999 128 128 0.01 Streptococcus pneumoniae 16 128 0.1 Streptococcus faecalis 1362/3 128 128 16 Haemophilus influenzae 128 128 0.01 Neisseria gonorrheae 64 128 0.1 Escherichia coli 1074 128 128 128 Candida albicans 128 128 Aspergillus fumigatus 16 32 Aspergillus niger 32 64 …”