Previously described cases of streptomycin inactivation by R-factor carrying strains of E. coli have not lead to any measurable decrease in antimicrobial potency in the bulk substrate toward the culture. In these cases each cell inactivates only a few molecules. Out of 1, 800 strains of E. coli we have isolated five strains which inactivate streptomycin in large amounts giving a final concentration of the inactivation product of 0.25 mg/ml in 36 hours. Unlike all other streptomycin-resistant strains investigated these five strains were sensitive to butyl-streptomycylamine, a streptomycin derivative acting in the same way as streptomycin. The crude inactivation product has been isolated. Inorganic phosphate is liberated by treatment with alkaline phosphatase resulting in a streptomycin-like compound without any antimicrobial activity.

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By mutation and strain improvement techniques idiotrophs of Micromonospora purpurea, the gentamicin-producing organism, were obtained which require an exogenous source of 2-deoxystreptamine in order to produce gentamicin. Streptamine incorporation afforded a mixture of 2-hydroxygentamicin C as a complex of essentially the C₁ and C₂ components whereas 2-deoxystreptamine when incorporated by the same idiotroph afforded the same mixture of C₁, C₂ and C_1a gentamicins as the parent (m₁) organism. The 2-hydroxygentamicin C complex exhibited broad-spectrum antibiotic activity with an in vitro potency less than that for the gentamicin C complex, but with greater activity against selected gentamicin C resistant organisms. The LD₅₀ (i.v.) in mice of the 2-hydroxygentamicin C complex indicated that it had approximately half the toxicity of the gentamicin C complex. 2, 5-Dideoxystreptamine afforded a C₁, C₂, and C_1a mixture of 5-deoxygentamicins, which also had broad spectrum activity, and exhibited improved activity against several gentamicin-acetylating strains of resistant bacteria. The LD₅₀ (i.v.) in mice of the 5-deoxygentamicin C complex indicated that it was about 2.5 times more toxic than the gentamicin C complex. Two derivatives of 2, 5-dideoxystreptamine afforded the same mixture of 5-deoxygen-tamicins. 2-Epistreptamine upon supplementation to a broth containing growing cultures of these idiotrophs also produced antibiotic.

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A mutant of Micromonospora purpurea, which produces the gentamicin complex only when 2-deoxystreptamine is added to the fermentation medium, produces a new antibiotic complex, 2-hydroxygentamicin, when streptamine or 2, 4, 6/3, 5-pentahydroxycyclohexanone is added to the fermentation medium. This mutant also produces the gentamicin complex when 2, 4/3, 5-tetrahydroxycyclohexanone is added to the fermentation medium. The C₁ and C₂ components of 2-hydroxygentamicin have broad spectrum in vitro antibacterial activity similar to the gentamicin C₁ and C₂ components, but with greater activity against some gentamicin-resistant strains.

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The incorporation of uniformly ¹⁴C-labeled compounds into the streptothricin-type antibiotic nourseothricin was studied with a strain of Streptomyces noursei JA 3890b. 6.5% of radioactivity from U-¹⁴C-L-arginine was incorporated into the antibiotic, while glutamic acid, aspartic acid, alanine, proline, glycine and leucine displayed much lower incorporations. Furthermore, 95% of the activity incorporated from arginine was located in the streptolidine moiety supporting the suggestion that this subunit of streptothricin antibiotics is formed via the dehydroarginine pathway.

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A gene coding for desensitized L-threonine dehydratase was transduced with phage PS20 into a leucine accumulator of Serratia marcescens Sr41. The transductant converted L-threonine to α-ketobutyrate, a precursor of both norvaline and isoleucine. An isoleucine-valine auxotroph of the transductant accumulated large amount of norvaline from L-threonine as well as from D-threonine.

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Amphotericin B methyl ester (AME), the chemically modified derivative of amphotericin B, induced a concentration-dependent growth stimulatory effect on B82 mouse cells as indicated by increased 24- and 72-hour viable cell number, growth rate and DNA and RNA synthesis. In contrast, AME was not growth promoting toward RAG mouse cells or B82-RAG somatic cell hybrids, while hybrid cells exhibited the increased AME resistance pattern of B82 parental cells. A dissociation between the phenotypic expression of growth stimulation and polyene sensitivity was demonstrated in intraspecific mouse hybrids.

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