The effects of a variety of oxazolidinones, with different antibacterial potencies, including linezolid, on mitochondrial protein synthesis were determined in intact mitochondria isolated from rat heart and liver and rabbit heart and bone marrow. The results demonstrate that a general feature of the oxazolidinone class of antibiotics is the inhibition of mammalian mitochondrial protein synthesis. Inhibition was similar in mitochondria from all tissues studied. Further, oxazolidinones that were very potent as antibiotics were uniformly potent in inhibiting mitochondrial protein synthesis. These results were compared to the inhibitory profiles of other antibiotics that function by inhibiting bacterial protein synthesis. Of these, chloramphenicol and tetracycline were significant inhibitors of mammalian mitochondrial protein synthesis while the macrolides, lincosamides, and aminoglycosides were not. Development of future antibiotics from the oxazolidinone class will have to evaluate potential mitochondrial toxicity.
Aim: To analyse the growth of Bacillus anthracis during simulations of the UK anthrax vaccine manufacturing process.
Methods and Results: Simulated vaccine production runs were performed using the toxigenic, acapsulate Sterne 34F2 strain of B. anthracis in semi‐defined medium. After rising during the logarithmic growth phase, the pH of the culture starts to fall at about 18 h from pH 8·7 to reach <7·6 at 26 h, coincident with consumption of glucose and optimal production of protective antigen (PA; 7·89 g ml−1, SD 1·0) and lethal factor (LF; 1·85 g ml−1, SD 0·29). No increased breakdown of toxin antigens was seen over the 26–32 h period. When glucose was exhausted, amino acids (principally serine) were utilized as an alternative carbon source. Sporulation was not observed during the 32 h.
Conclusions: PA and LF, the principal constituents in the UK anthrax vaccine, undergo little degradation during vaccine fermentation. The vaccine manufacturing process is robust and reproducible.
Significance and Impact of the Study: This is the first detailed analysis of the manufacturing process used for the UK acellular anthrax vaccine; insight gained into the process will support continued and safe vaccine manufacture.
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