Polyamines are required for optimal growth in most cells; however, polyamine accumulation leads to inhibition of cellular growth. To reduce intracellular polyamine levels, spermidine is monoacetylated in both prokaryotes and eukaryotes. In Escherichia coli, the speG gene encodes the spermidine acetyltransferase, which transfers the acetyl group to either the N-1 or N-8 position. In addition to polyamine accumulation, stress conditions, such as cold shock, cause an increase in the level of spermidine acetylation, suggesting an adaptive role for reduced polyamine levels under stressful growth conditions. The effect of spermidine accumulation on the growth of E. coli at low temperature was examined using a speG mutant. At 37°C, growth of the speG mutant was normal in the presence of 0.5 or 1 mM spermidine. However, following a shift to 7°C, the addition of 0.5 or 1 mM spermidine resulted in inhibition of cellular growth or cell lysis, respectively. Furthermore, at 7°C, spermidine accumulation resulted in a decrease in total protein synthesis accompanied by an increase in the synthesis of the major cold shock proteins CspA, CspB, and CspG. However, the addition of 50 mM Mg Polyamines, such as spermidine and putrescine, are present in virtually all cells (25, 33). These polycations have pleiotropic properties, which can influence several cellular processes. They can bind to nucleic acids, stabilize membranes, and stimulate the activity of several enzymes, such as RNA polymerase (1,31,34). Found in the ribosomal fraction, polyamines enhance the synthesis of several proteins and stimulate the in vivo assembly of the Escherichia coli 30S ribosomal subunit (7,13,21,35).Although intracellular polyamine is required for optimal growth, polyamine accumulation can lead to inhibition of cellular growth (11,25,26,33). The addition of spermidine to cell cultures of mouse FM3A cells results in a decrease in cell growth accompanied by inhibition of protein synthesis (11). To prevent polyamine toxicity in eukaryotes, polyamine catabolism is initiated by the monoacetylation of spermidine and spermine catalyzed by spermidine/spermine N 1 -acetyltransferase (SSAT) (4). The acetylpolyamines are then either further oxidized by polyamine oxidase or excreted from the cell.In E. coli, the speG gene encodes spermidine acetyltransferase (SAT), which transfers the acetyl group to either the N-1 or N-8 position of the polyamine (2,8,20). SAT is required to reduce the spermidine level, since the addition of exogenous spermidine to a speG mutant results in intracellular accumulation of spermidine (9). Furthermore, the excess spermidine causes decreased protein synthesis and cell viability during the stationary phase of growth (9). Acetylation serves to convert the polyamine to a physiologically inert form; acetylpolyamines cannot substitute for polyamines in RNA binding, in the enhancement of growth of an E. coli polyamine-deficient mutant, or in the stimulation of in vitro translation (18). Neither spermidine-deacetylating activity nor polyamin...

No abstract

Several studies of the efficacy of intradermal postexposure rabies vaccination have shown that this procedure is safe, effective, and cost saving. Less is known about the reliability of the present World Health Organization (WHO)-approved intradermal preexposure regimen, which consists of three 0.1-mL doses that are generally given on days 0, 7, and 28. Previous studies have shown that neutralizing antibody responses are lower and of shorter duration in subjects given the reduced-dose intradermal regimen. Thus, it is still uncertain whether the WHO-recommended single intramuscular or intradermal booster injections given on days 0 and 3 would prevent death in all cases. In this preliminary study, we evaluated titers of neutralizing antibody in Thai student volunteers given two simulated postexposure boosters, as recommended by WHO, and we compared these volunteers to a group given vaccine intramuscularly. We observed a lower, although adequate, accelerated immune response in those given the preexposure series and postexposure boosters intradermally.