Streptomycin activity

Little or no loss of antimicrobial activity was further observed after fermentation of raw sausages containing streptomycin (6). However, smoking/scalding processes could cause a 32-45% reduction of the streptomycin activity (7). When semi- or fully preserved sausages were heated at 90-95 C for 1 h, the microbiological activity of the contained streptomycin exhibited a 50% reduction of the initial dose (8) however, some of the initial activity could be demonstrated in the juices exuded from the heated sausages even when the temperature was raised to 120-125 C. 

Paine jr., T.F., and F.Lipmann No anti-streptomycin activity shown by... 

In 1939 the isolation of a mixture of microbial products named tyrotbricin from a soil bacillus was described. Further investigation showed this material to be a mixture of gramicidin and tyrocidine. In rapid succession the isolation of actinomycin (1940), streptothricin (1942), streptomycin (1943), and neomycin (1949), produced by Streptomjces were reported and in 1942 the word antibiotic was introduced. Chloramphenicol, the first of the so-called broad spectmm antibiotics having a wide range of antimicrobial activity, was discovered in 1947. Aureomycin, the first member of the commercially important tetracycline antibiotics, was discovered in 1948. 

Before the discovery of streptomycin, pyrazinamide (126) was one of the front runners in the treatment of tuberculosis. A broad spectrum of biological activity has been associated with pyrazine derivatives, ranging from the herbicidal activity of (127) to antibiotic activity... 

Substitution of an amino group into the molecule affords an iigent with antibacterial activity. Although seldom used alone, l, ira- aminosalicylic acid (PAS, 7) has been employed as an adjunct Id streptomycin and isoniazid in treatment of tuberculosis. 

Most aiititubercular drag s are bacteriostatic (slow or retard the growth of bacteria) against the M. tuberculosis bacillus. These dm usually act to inhibit bacterial cell wall synthesis, which slows the multiplication rate of the bacteria. Only isoniazid is bactericidal, with rifampin and streptomycin having some bactericidal activity. 

Discovery of Kanamycin, and Establishment oflMC. Chloramphenicol, chlor- and oxy-tetracyclines, and pyridomycin (H. Umezawa, 1967) were active, in in vitro experiments, against strains of tuberculosis, but these drugs, in contrast to streptomycin, were clinically inactive. H. Umezawa... 

Stiepton dn was isolated by Waksman in 1944, and its activity against M tuberculosis ensured its use as a primaiy ding in the treatment of tuberculosis. Unfortunately, its ototoxicity and the rapid development of resistance have tended to modify its usefulness, and although it still remains a front-hne dmg against tuberculosis it is usually used in combination with isoniazid and p(4)-aminosalicyhc acid (section 11.5). Streptomycin also shows activity against other types of bacteria,... 

Figure 12.8. Transformation activity (streptomycin resistance) of a DNA-yeast extract mixture as a function of illumination time. (Reproduced with permission from Ref. 74.)...

The best results are obtained when 100 mg I. 1 streptomycin is added 48-50 h after the initiation of germination. With streptomycin treatment, 100-400% increases in recombinant protein expression have been obtained. The accumulation of both Rubisco subunits is prevented (Figure 3.7). The specific activity of GUS increases 2.5-fold when streptomycin is used (Figure 3.8). 

Fig. 3.8 Transgenic rapeseeds expressing the gusA reporter gene were germinated in an airlift tank with streptomycin added to the medium (100 mg L 1). Streptomycin was added 0, 38, 42 or 50 h after germination. When streptomycin is added after 50 h, a 2.5-fold increase in GUS activity can be seen. This indicates the importance of correct timing when streptomycin is added to inhibit endogenous Rubisco gene expression.

The answer is a. (Hardman, pp 1105-1108.) The activity of streptomycin is bactericidal for the tubercle bacillus organism. Other aminoglycosides (e.g., gentamicin, tobramycin, neomycin, amikacin, and kanamycin) have activity against this organism but are seldom used clinically because of toxicity or development of resistance. 

The answer is d. (Hardman, pp 1105-1108.) The bactericidal activity of streptomycin and other aminoglycosides involves a direct action on the 305 ribosomal subunit, the site at which these agents both inhibit protein... 

The cell-bound amylopullulanase was solubilized with detergent and lipase. It was then purified to homogeneity by treatment with streptomycin sulfate and ammonium sulfate, and by DEAE-Sephacel, octyl-Sepharose and puUulan-Sepharose column chromatography (12). The final enzyme solution was purified 3511-fold over the crude enzyme extract with an overall recovery of 42% and had a specific activity of 481 units/mg protein. The average molecular weight of the enzyme was 136,500 determined by gel filtration on Sephacryl S-200 and SDS-PAGE, and it had an isoelectric point at pH 5.9. It was rich in acidic and hydrophobic amino acids. The purified enzyme was quite thermostable in the absence of substrate even up to 90°C with essentially no loss of activity in 30 min. However, the enzyme lost about 40% of its original activity at 95 C tested for 30 min. The optimum tenq)erature for the action of the purified enzyme on pullulan was 90°C. However, the enzyme activity rapidly decreased on incubation at 95°C to only 38% of the maximal 30 min. The enzyme was stable at pH 3.0-5.0 and was optimally active at pH 5.5. It produced only maltotriose and no panose or isopanose from pullulan. 

Extractions traditionally have been performed using buffers (j ) the same used to obtain the maximum response in standard curves. Unfortunately this has been a major failing of the plate diffusion assay systems. It is rare that the pH can be adjusted to the optimum necessary for greatest response simply by blending a matrix with buffer. As much as a 30 to 40% loss of activity can occur by not adjusting the pH properly analysis for residues of the streptomycins and erythromycin, for example, can yield results 20% lower by having the pH of the analyte 0.2 units below 8.0 if the pH is 0.5 units below 8.0, the loss of potency approaches 50% (14-15). 

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