Phylogenetic classification of serotype III group B streptococci on the basis of hylB gene analysis and DNA sequences specific to restriction digest pattern type III-3.

Previous work divided serotype III group B streptococci (GBS) into 3 major phylogenetic lineages (III-1, III-2, and III-3) on the basis of bacterial DNA restriction digest patterns (RDPs). Most neonatal invasive disease was caused by III-3 strains, which implies that III-3 strains are more virulent than III-2 or III-1 strains. In the current studies, all RDP III-3 and III-1 strains expressed hyaluronate lysase activity; however, all III-2 strains lack hyaluronate lysase activity, because the gene that encodes hyaluronate lysase, hylB, is inactivated by IS1548. Subtractive hybridization was used to identify 9 short DNA sequences that are present in all the III-3 strains but not in any of the III-2 or III-1 strains. With 1 exception, these III-3-specific sequences were not detected in nonserotype III GBS. These data further validate the RDP-based subclassification of GBS and suggest that lineage-specific genes will be identified, which account for the differences in virulence among the lineages.

Thiazolidine prodrugs of cysteamine and cysteine as radioprotective agents.

The need for protection against the toxic effects of ionizing radiation comes from many different directions: occupational exposure, nuclear accidents, environmental sources and protection of normal tissue during the therapeutic irradiation of cancer. Sulfhydryl-containing compounds, including cysteamine and L-cysteine, have long been known to possess radioprotective properties, but their therapeutic utility is limited by their side effects at radioprotective doses. To avoid this drawback, thiazolidine prodrugs of cysteamine and L-cysteine were prepared by the condensation of each thioalmine with the aldose monosaccharides, D-ribose and D-glucose, producing RibCyst, GlcCyst, RibCys and GlcCys. The prodrugs were designed to liberate the parent thiolamine nonenzymatically, after ring opening and hydrolysis, which is then available to function as a radioprotective agent. Cysteamine's inherent toxicity, measured using Chinese hamster V79 cells growing in culture, was completely eliminated, even at concentrations as high as 25 mM, by providing the thiolamine in the form of a prodrug. Good protection against radiation-induced lethality was demonstrated by the cysteamine prodrugs using a clonogenic assay. Protection against radiation-induced DNA single-strand breaks, as measured by alkaline elution, was also shown by both RibCyst and GlcCyst; this activity was higher than that exhibited by either cysteamine or WR-1065. The L-cysteine prodrugs, RibCys and GlcCys, also possessed radioprotective abilities under most of the conditions studied. Protection against DNA damage was comparable between L-cysteine, WR-1065 and RibCys.