Characterization of a Monoclonal Antibody Specific for Lipoteichoic Acid from Various Gram-Positive Bacteria

A hybrid cell line, 3G6, producing monoclonal antibody (mAb) against the polyglycerophosphate (PGP) backbone of lipoteichoic acids has been derived by the polyethylene glycol-induced fusion of mouse myeloma cells and spleen cells from mice immunized with partially purified glucosyltransferase from culture supernatant of Streptococcus mutans strain 6715. Immunodiffusion tests and ELISA revealed that the antibody reacted with purified PGP from group A Streptococcus pyogenes strain Sv as well as crude phenol-water and saline extracts of various gram-positive bacteria except for a few species such as biotype B S. sanguis, Micrococcus sp., and Actinomyces viscosus. Whole cells of serotype b S. mutans and Staphylococcus epidermidis were agglutinated upon addition of 3G6 mAb, while those of most other species were not significantly affected by this procedure. A hapten inhibition study showed that glycerophosphate was only a potent inhibitor of passive hemagglutination reactions between LTA coated sheep erythrocytes and 3G6 mAb.     

New target for inhibition of bacterial RNA polymerase: 'switch region'

A new drug target - the 'switch region' - has been identified within bacterial RNA polymerase (RNAP), the enzyme that mediates bacterial RNA synthesis. The new target serves as the binding site for compounds that inhibit bacterial RNA synthesis and kill bacteria. Since the new target is present in most bacterial species, compounds that bind to the new target are active against a broad spectrum of bacterial species. Since the new target is different from targets of other antibacterial agents, compounds that bind to the new target are not cross-resistant with other antibacterial agents. Four antibiotics that function through the new target have been identified: myxopyronin, corallopyronin, ripostatin, and lipiarmycin. This review summarizes the switch region, switch-region inhibitors, and implications for antibacterial drug discovery.     

Appearance of New Protein Species on the Cell Surface during Sexual Differentiation in the Heterobasidiomycetous Yeast,Tremella mesenterica

The effects of neural blockers on the pancreatic enzyme secretion in response to an intraluminal infusion of soybean trypsin inhibitor and HCl were investigated. The stimulation of pancreatic enzyme secretion upon the intraluminal infusion of soybean trypsin inhibitor was not blocked by atropine, but was completely blocked by guanethidine. The intraluminal infusion of 0.08 n HCl, which is known as a potent secretagogue of secretin, caused a rapid augmentation of trypsin output, which was not blocked by atropine or guanethidine. Preinjection of CR-1392 (1.5 mg/kg, i.p.), which is a strong cholecystokinin receptor antagonist, completely blocked the pancreatic response to soybean trypsin inhibitor, but not that to 0.08 n HCl. This inferred that guanethidine specifically suppressed the CCK-release from the small intestine.

These findings suggest that the pancreatic enzyme secretion in response to soybean trypsin inhibitor is mainly mediated by CCK, and that adrenergic modulation would be involved in the CCK-mediated pancreatic enzyme secretion in response to soybean trypsin inhibitor.     

Antibiotic Complex SP-351 Produced by a Psychrophile,Streptomyces sp. No. 351

In the course of a screening study for antibiotics using psychrophilic microorganisms a water-insoluble antibiotic complex, SP–351, was found in the culture filtrate of a psychrophilic actinomycete, strain No. 351. This active principle was isolated and characterized as a cyclicpolylactone antibiotic. The SP–351-producing strain was classified as a facultative psychrophile and identified as Streptomyces phaeochromogenes.

The main components of the antibiotic complex SP–351 changed with the composition of the culture medium but not with culture temperatures. Component A was exclusively produced in a medium composed of roasted soybean powder and glycerol; components B and C in a medium composed of soybean, glycerol and potassium nitrate; and components A and D in a synthetic medium containing a hydrocarbon, alcohol or ester as the sole carbon source. Maximum production of SP–351 from n-paraffin and methyl acetate was 10 and 15 mcg/ml, respectively.

SP–351 showed strong antibacterial activity against Gram-positive bacteria and acid-fast bacteria at 0.1~0.3 mcg/ml concentrations.     

Daily ethanol exposure during late ovine pregnancy: physiological effects in the mother and fetus in the apparent absence of overt fetal cerebral dysmorphology

High levels of ethanol (EtOH) consumption during pregnancy adversely affect fetal development; however, the effects of lower levels of exposure are less clear. Our objectives were to assess the effects of daily EtOH exposure (3.8 USA standard drinks) on fetal-maternal physiological variables and the fetal brain, particularly white matter. Pregnant ewes received daily intravenous infusions of EtOH (0.75 g/kg maternal body wt over 1 h, 8 fetuses) or saline (8 fetuses) from 95 to 133 days of gestational age (DGA; term ～145 DGA). Maternal and fetal arterial blood was sampled at 131-133 DGA. At necropsy (134 DGA) fetal brains were collected for analysis. Maternal and fetal plasma EtOH concentrations reached similar maximal concentration (～0.11 g/dl) and declined at the same rate. EtOH infusions produced mild reductions in fetal arterial oxygenation but there were no changes in maternal oxygenation, maternal and fetal Pa(CO(2)), or in fetal mean arterial pressure or heart rate. Following EtOH infusions, plasma lactate levels were elevated in ewes and fetuses, but arterial pH fell only in ewes. Fetal body and brain weights were similar between groups. In three of eight EtOH-exposed fetuses there were small subarachnoid hemorrhages in the cerebrum and cerebellum associated with focal cortical neuronal death and gliosis. Overall, there was no evidence of cystic lesions, inflammation, increased apoptosis, or white matter injury. We conclude that daily EtOH exposure during the third trimester-equivalent of ovine pregnancy has modest physiological effects on the fetus and no gross effects on fetal white matter development.     

Effects of CH-19 Sweet, a non-pungent cultivar of red pepper, on sympathetic nervous activity, body temperature, heart rate, and blood pressure in humans

We investigated the changes in autonomic nervous activity, body temperature, blood pressure (BP), and heart rate (HR) after intake of the non-pungent pepper CH-19 Sweet and of hot red pepper in humans to elucidate the mechanisms of diet-induced thermogenesis (DIT) due to CH-19 Sweet. We found that CH-19 Sweet activates the sympathetic nervous system (SNS) and enhances thermogenesis as effectively as hot red pepper, ant that the heat loss effect due to CH-19 Sweet is weaker than that due to hot red pepper. Furthermore, we found that intake of CH-19 Sweet does not affect systolic BP or HR, while hot red pepper transiently elevates them. These results indicate that DIT due to CH-19 Sweet can be induced via the activation of SNS as well as hot red pepper, but that the changes in BP, HR, and heat loss effect are different between these peppers.     

Synthesis and antibacterial activity of C11, C12-cyclic urea analogues of ketolides

C11, C12-cyclic urea analogues of ketolides were designed and synthesized by use of a novel ketene acetal intermediate. This intermediate enabled introduction of an amino group at C12 stereospecifically and in high yield. The resulting cyclic urea ketolides appear to have in vitro activity similar to that of telithromycin which contains a C11, C12 cyclic carbamate moiety. Some of the C2 fluorinated compounds have improved potency against erm-containing Streptococcus pyogenes.