Function of the <Emphasis Type="Italic">rel</Emphasis> Gene in <Emphasis Type="Italic">Escherichia coli</Emphasis>

Sokawa et al. suggest that rel^- strains of Escherichia coli possess abnormal protein synthesizing machinery, which cannot carry out normal protein synthesis when the supply of amino-acids is limited.     

“Pleiotypic Response”

A hypothesis has been developed to relate stringent control in bacteria to a set of interactions involved in the regulation of growth of transformed and untransformed mammalian cells.     

Inhibition of DNA Synthesis but not of Poly-dAT Synthesis by the Arabinose Analogue of Cytidine <Emphasis Type="Italic">in vitro</Emphasis>

Kimball and Wilson¹ reported that the arabinose analogue of cytidine (ara-C) inhibited DNA polymerase in a crude extract prepared from Ehrlich ascites cells. Furth and Cohen² observed cytosine arabinoside triphosphate (ara-CTP) inhibited DNA polymerase in extracts from either calf thymus or bovine lymphosarcoma tissue, although these investigators³ had already found no effect of ara-CTP on DNA polymerase from Escherichia coli. The inhibition in both of these cases could be substantially reversed by dCTP; but incorporation of the arabinose nucleotide (ara-CMP) into DNA could not be unequivocally demonstrated. Graham and Whitmore⁴ reported the incorporation of ara-C into DNA in vivo and the inhibition of a DNA polymerase from L cells by ara-CTP. They found that ara-CMP was initially incorporated into small DNA strands but subsequently appeared in long strands. Momparler⁵ has presented evidence that, in vitro, ara-C incorporation was limited to the 3′-hydroxyl end of DNA chains. Such incorporation might be expected to block further chain elongation but this expectation was not supported by the evidence presented by Graham and Whitmore.     

Endopeptidase Activity of Phage λ-Endolysin

JACOB and Fuerst^1,2 demonstrated the presence of a bacteriolytic enzyme (λ-endolysin) in the induced cultures of lysogenic Escherichia coli K12 (λ). The enzyme was later identified as the product of gene R; of phage λ³ which is involved in bacterial lysis at the end of a latent period. The enzyme is apt to form spheroplast-like structures in E. coli² and one would therefore expect its substrate to be murein.     

Selective Utilization of Pyrimidine Deoxyribonucleosides for Deoxyribonucleic Acid Synthesis in Pneumococcus

When pyrimidine deoxyribonucleosides are supplied to growing cultures of Diplococcus pneumoniae, they are selectively used for incorporation into deoxyribonucleic acid (DNA). Differently labeled molecules of deoxyuridine, thymidine, and deoxycytidine were used to study the precursor pathways of this organism. Each of these preformed pyrimidine deoxynucleosides is incorporated intact (i.e., without cleavage of the glycosidic bond) and is predominantly recoverable as DNA thymidine. During the utilization of deoxycytidine and deoxyuridine by pneumococci, large proportions of the available precursor are converted to free thymidine, which is secreted back into the growth medium. The biochemical pathways for selective incorporation into DNA and the regulation of concentrations of intracellular thymidine compounds by excretion of free thymidine are discussed.     

Naturally occurring peptidoglycan variants of Streptococcus pneumoniae.

Analysis by high-performance liquid chromatography of the stem peptide composition of cell walls purified from a large number of pneumococcal strains indicates that these bacteria produce a highly conserved species-specific peptidoglycan independent of serotype, isolation date, and geographic origin. Characteristic features of this highly reproducible peptide pattern are the dominance of linear stem peptides with a monomeric tripeptide, a tri-tetra linear dimer, and two indirectly cross-linked tri-tetra dimers being the most abundant components. Screening of strains with the high-performance liquid chromatography technique has identified two naturally occurring peptidoglycan variants in which the species-specific stem peptide composition was replaced by two drastically different and distinct stem peptide patterns, each unique to the particular clone of pneumococci producing it. Both isolates were multidrug resistant, including resistance to penicillin. In one of these clones--defined by multilocus enzyme analysis and pulsed-field gel electrophoresis of the chromosomal DNAs--the linear stem peptides were replaced by branched peptides that most frequently carried an alanyl-alanine substituent on the epsilon amino group of the diamino acid residue. In the second clone, the predominant stem peptide species replacing the linear stem peptides carried a seryl-alanine substituent. The abnormal peptidoglycans may be related to the altered substrate preference of transpeptidases (penicillin-binding proteins) in the pneumococcal variants.     

Microbial transformation of azacarbazoles X: Regioselective hydroxylation of 5,11-dimethyl-5H-indolo [2,3-b]quinoline, a novel DNA topoisomerase II inhibitor, by Rhizopus arrhizus

Summary Microbial transformation of cytotoxic 5,11-dimethyl-5H-indolo[2,3-b]quinoline (a compound displaying antitumor activity and affecting the activity of calf thymus DNA topoisomerase II) was performed by the Rhizopus arrhizus strain and yielded a 9-hydroxy derivative. The metabolite obtained displayed a stronger cytotoxity against KB cells than the parent compound (ID₅₀=0.001 mol/mL), and stimulated also the formation of calf thymus topoisomerase II mediated pSP65 DNA cleavage in vitro at the concentration of 3 M. Being analogous to 9-hydroxyellipticine (which is an antitumor alkaloid), this novel indolo[2,3-b] quinoline derivative can be regarded as a novel potential antitumor agent.