Disease relevance of Blasticidin S

• They are based on two genes for the resistance to Blasticidin S (BlaS) and on the thymidine kinase (Tk) gene of herpes simplex virus (HSV) [1].
• The blasticidin S-resistance gene (bsr), isolated from Bacillus cereus K55-S1 strain, was inserted into pSV2 plasmid vector and introduced into cultured mammalian cells by transfection [2].
• A gene (bls) encoding a blasticidin S-acetyltransferase from Streptoverticillum sp. JCM4673 was cloned in the Streptomyces plasmid pIJ702 and expressed in S. lividans 1326 [3].
• Recombinant f1 phages carrying a shuttle vector pKA1M for expression of blasticidin S deaminase were introduced into monkey COS7 cells by mixing with dioctadecylamidoglycylspermine (DOGS) [4].
• As a prerequisite, a vector was generated containing a blasticidin resistance cassette for selection in the Escherichia coli host strain KS272 (pKOBEG) and a phleomycin resistance cassette for selection in P. anserina [5].

High impact information on Blasticidin S

• CENP-A and heterochromatin were assembled over noncentromeric DNA, including the gene blasticidin, into nonoverlapping domains [6].
• Polyamines affect diversely the antibiotic potency: insight gained from kinetic studies of the blasticidin S AND spiramycin interactions with functional ribosomes [7].
• Kinetics revealed that blasticidin S, after a transient phase of interference with the A-site, is slowly accommodated near to the P-site so that peptide bond is still formed but with a lower catalytic rate constant [7].
• New positive/negative selectable markers for mammalian cells on the basis of Blasticidin deaminase-thymidine kinase fusions [1].
• To develop a robust cell culture system capable of supporting the efficient growth of wt HAV, we transfected different cell lines with in vitro RNA transcripts of wt HAV containing the blasticidin resistance gene [8].

Chemical compound and disease context of Blasticidin S

• Biosynthesis of the antifungal agent blasticidin S in Streptomyces griseochromogenes requires the formation of free cytosine [9].
• Cytosinine--the nucleoside portion of blasticidin S--and pyridoxal phosphate were incubated with cell-free extracts of Streptomyces griseochromogenes prepared in D2O [10].
• Purification and characterization of a puromycin-hydrolyzing enzyme from blasticidin S-producing Streptomyces morookaensis [11].
• 5-Hydroxymethylblasticidin S and blasticidin S from Streptomyces setonii culture A83094 [12].
• Arginomycin, C18H28N8O5, which inhibits the growth of Gram-positive bacteria and fungi in vitro, is structurally related to blasticidin S and found to be relatively non-toxic [13].

Biological context of Blasticidin S

• At high concentrations of blasticidin S (>10 x K(i)), a second drug molecule binds to a weaker binding site on ribosomes, and this may account for the onset of a subsequent mixed-noncompetitive inhibition phase [7].
• Transfectants in which several copies of bsr had been integrated into the genome were highly resistant to blasticidin S [2].
• Blasticidin S base-pairs with the P-loop and thereby mimics C74 and C75 of a P-site bound tRNA [14].
• This dicistronic gene conferred blasticidin S-resistance to 293 cells besides luciferase activity, when examined not only by transfection but also by transduction using AAV vectors [15].
• The blasticidin S biosynthesis gene cluster was cloned from S. griseochromogenes and the pathway heterologously expressed in S. lividans from a cosmid harboring a 36.7-kb fragment of S. griseochromogenes DNA [16].

Anatomical context of Blasticidin S

• The bsr gene was integrated into the genome and conferred blasticidin S resistance on HeLa cells [2].
• We have also generated retroviral vectors that allow rapid pharmacologic selection of human keratinocytes without interfering with the potential of these cells to regenerate epidermis in vivo--we determined that blasticidin is superior to the commonly used neomycin [17].
• Anisomycin, trichodermin, trichodermol, trichothecin, fusarenon X, sparsomycin and blasticidin S inhibit peptide bond formation on these polysomes, whereas diphtheria toxin, pederine, cycloheximide and cryptopleurine block translocation [18].
• The toxic effects of blasticidin S were noted in ectodermal tissues including the skin, conjunctiva, cornea, and intestine [19].
• Each cell line of a panel of monochromosomal mouse-human somatic cell hybrids was individually transduced with an HIV vector encoding both cycT1 and blasticidin resistance (HIV-CIB) [20].

Associations of Blasticidin S with other chemical compounds

• Ribosomal binding sites were investigated for the diverse group of antibiotics: anisomycin, anthelmycin, blasticidin S, bruceantin, carbomycin, chloramphenicol, griseoviridin, narciclasine, T2 toxin, tylosin and virginiamycin M1 all of which are considered to inhibit the peptidyl transferase reaction by different mechanisms [21].
• In the case of yeast ribosomes, blasticidin is a relatively good competitor of sparsomycin interaction, but anisomycin, trichodermin, and narciclasin are not [22].
• Assembly of the protected cytosinine (32) and blastidic acid (47) by the BOP method in the presence of HOBt, and finally elaboration to 1 by deprotection of the fully protected 54 established the total synthesis of blasticidin S (1) [23].
• Alkaline phosphatase synthesis is more sensitive than total protein synthesis to tetracyclin and spectinomycin, but not to sparsomycin, streptomycin, chloramphenicol, kasugamycin, blasticidin S or thiostrepton; it is slightly more resistant than total protein synthesis to the latter two antibiotics [24].
• Fluctuation analyses revealed that these mutator mutants have increased rates of spontaneous mutation at 3 genetic loci tested (resistance to ouabain, blasticidin S and tunicamycin) [25].

Gene context of Blasticidin S

• A gene bls1 was linked to an ilv3 gene located on the right arm of chromosome X. The resistant phenotypes from both genes were not associated with ribosomes known to be target sites of Blasticidin S, when analyzed by poly(U)-directed polyphenylalanine synthesis [26].
• The functional expression of these genes was demonstrated by western blot analysis with MSP1 specific antibodies and by a blasticidin growing assay [27].
• Treatment with alpha interferon A/D cured the blasticidin-resistant Huh7 cells of the HAV infection [8].
• Crystallization and preliminary X-ray diffraction studies of blasticidin S deaminase from Aspergillus terreus [28].
• Expression of the blasticidin S deaminase gene (bsr) in tobacco: fungicide tolerance and a new selective marker for transgenic plants [29].

Analytical, diagnostic and therapeutic context of Blasticidin S

• The blasticidin S biosynthesis gene cluster from Streptomyces griseochromogenes: sequence analysis, organization, and initial characterization [16].
• Transformation vectors conferring resistance to neomycin and/or blasticidin were introduced into the cell as a calcium phosphate coprecipitate or by electroporation [30].
• Enzyme immunoassay of blasticidin S with high sensitivity: a new and convenient method for preparation of immunogenic (hapten-protein) conjugates [31].
• Following transfection of mutant parasites that contained other well-established selectable marker genes (HYG, NEO, BLE, PAC and SAT), clones resistant to 10 microg ml(-1) blasticidin S were shown by PCR and Southern blotting to have integrated the cassettes by homologous recombination [32].
• For the genes we have tested in these studies (myosin heavy chain kinases B and C), the efficiency of the double gene targeting event is found in the range of 2%-5% of all blasticidin-resistant colonies following the transfection step [33].

References