DESCRIPTIONS OF ANTIBIOTICS 



1(17 



bacteria. Not active on gram negative bacteria, 

 mycobacteria, or fungi. 



Toxicity: 25 mg per kg lethal to rats. 



Reference: 1. Cercos, A. P. Rev. invest, agr. 

 2: 147-156, 1948. 



ActiiioiiiN celin 



Produced by: Sireploniyces albiis and Strepfo- 

 inyces sp. (1 , 2). 



Nenidiks: Antibacterial factor may be similar to 

 mycomycin. 



In discussing Feist mantel's (5) work on the 

 close genetic relationship of the tuberculosis or- 

 ganism and the actinomycetes, based upon the 

 reactions given to tuberculin and by preparations 

 of Nocardia farcinica (the culture being desig- 

 nated as Streptothrix farcinica and the preparation 

 as "farcin poison") in guinea pigs, Mathieson et al. 

 (6) used in 1935 the term "actinomycetin" for the 

 extract of the culture designated by them as 

 Actinomyces farcinica. In 1937, Welsch (7) used 

 the designation "actinomycetin" for the sterile 

 filtrates of an actinomycete which possessed bac- 

 teriolytic properties. 



Method of extraction: I. Broth-filtrate at i)H 

 3.0 saturated to 75 per cent with ammonium sul- 

 fate. Precipitate taken up in water and reprecipi- 

 tated by addition of alcohol or acetone at low- 

 temperatures. The lipoid antibacterial substance 

 is extracted from the ammonium sulfate precipi- 

 tate with ether. Ether concentrated to dryness. 

 Residue taken up in ether, washed with 5 per cent 

 HCl, then extracted into 5 per cent NaOH. Re- 

 extracted into ether at acid pH, then into water at 

 alkaline pH several times (2). The two peptidases 

 (Fi and Fi) of the staphylolytic principle (see 

 below) can be separated by chromatography (3). 

 II. Culture-filtrate concentrated in vacuo at 35 °C 

 while Nj is bubbled through the solution. Con- 

 centrate treated with ammonium sulfate at 0°C 

 and at pH 8.0. Precipitate which forms taken up in 

 0.033 M K_.HP()4, centrifuged, and dialyzed against 

 distilled water at low temperature (4). 



Chemical and ph\;sical properties: Actinomycetin 

 is a general term for all the products, having activ- 

 ity on microorganisms, which are produced by S. 

 albus and other Streptoniyces spp. It includes the 

 following: (a) A colilytic principle, which is a 

 protein and an enzyme and is not identical to the 

 other proteases or enzymes present in the mixture 

 (1). (b) A staphylolytic principle containing two 

 peptidases, Fi and Fo , which are weakly active 

 alone, but synergistically active when combined. 

 Fi : White powder or "pic unique" crystals; 

 soluble in presence of electrolytes at >pH 5.0. 



Basic protein having no protease-like activity. 

 r2 : Brownish powder, not completely purified; 

 soluble in the presence of electrolytes at >pH 5.0. 

 No protease-like activity (3). (c) Lytic system 

 active on livimj streptococci , in part distinct from 

 the staphylolytic principle, (d) Activity on heat- 

 killed or living pncumococci represented by four 

 lytic agents, at least two of which differ from the 

 staphylolytic, colilytic, and streptolytic prin- 

 ciples, (e) Activity (lytic) on heat-killed but not 

 living gram-negative rods, occurring at 60-65°C 

 more rapidly than thermal sterilization (1). (f) 

 Other enzymes capable of digesting a variety of 

 substrates, such as casein, keratin, fibrin, fibrino- 

 gen, and mucin (3). (g) Antibacterial substance: 

 yellowish oily liquid. Acidic, probably unsatu- 

 rated fatty acids. Soluble in dilute alkali, petro- 

 leum ether, ether, acetone, chloroform, and carbon 

 tetrachloride. Less soluble in ethanol. Insoluble in 

 water and dilute acids. Loses activity on exposure 

 to air (2). (h) Antiviral substance: differs from the 

 other agents present in the complex. Thermolabile 

 (4). 



Biological activity: The antil)acterial substance 

 (g) is active on certain gram-positive bacteria 

 including M. phlei. Not active on gram-negative 

 bacteria except Flavobacterium sp. Very active on 

 certain protozoa, such as Paramecium, Glaucoma, 

 and Colpidium sp. Biological activity inhibited by 

 complex organic substances of a protein nature (2). 

 The colilytic principle (a) is active on heat-killed 

 E. coli (1). The staphylolytic principle (b) is active 

 on the cell walls of living gram-positive bacteria 

 (3). The antiviral substance (h) destroys the abil- 

 ity of red cells to be agglutinated by influenza 

 MF 1 (A) and Lee (B), but not influenza PR 8 (A) 

 or Newcastle disease virus; it destroys the hemag- 

 glutinin of influenza A (MF 1 and PR 8), influenza 

 B (Lee), and influenza C, l)ut not the Newcastle 

 disease virus; it destroys the infectivity of in- 

 fluenza A (PR 8) in contact tests in eggs and mice. 

 It is not active in ovo. It is active in protecting 

 mice from influenza infections, if given by the 

 intravenous route (4). 



Toxicity: 1 gm given intraperitoneally kills mice 

 in 18 hours or less (4). Antibacterial substance was 

 toxic to tomato plant roots at 5 /ug per ml (2). 



Utilization: Study of the structure of bacterial 

 cells (3). 



References : 



1. Welsch, M. et al. Proc. Intern. Congr. Bio- 



chem., 3rd Congr., Brussels, 1955, p. 413- 

 415. 



2. Welsch, M. Phenomenes d'antibiose chez les 



