Rifamycin Antibiotics Research Articles

Rational Chemotherapy: Inhibition of Polymerase Activity of Cancer Cells

To the Editor.— Recent data indicate that transformation of normal cells by tumor viruses appears to require altered DNA polymerase activity to transcribe new genetic information. Multiple workers have noted the promise for rational cancer chemotherapy of drugs depressing RNA-dependent DNA polymerase (reverse transcriptase) activity from tumor viruses and human acute leukemia cells. The drugs include rifamycin antibiotics (J Natl Cancer Inst49:761, 1972) and clinically promising sulfhydryl (SH)-inhibitors (Knock et al inOncology, Nov, 1972). At concentrations as low as 10μg/ml, clinically useful SH-inhibitors depress reverse transcriptase activity of human leukemic lymphocytes to 12% to 16% of control, activity usually far exceeding that of available rifamycins. The SH-inhibitors were selected by performing three in vitro sensitivity tests on hundreds of human cancers: namely agar plate assay, the Kondo sensitivity test, and radioactive tracer studies monitoring the incorporation of labeled precursors to DNA, RNA, and protein of tumors. The three

Transcription During the Development of Bacteriophage φ29: Definition of “Early” and “Late” φ29 Ribonucleic Acid

Bacteriophage phi29 messenger ribonucleic acid (mRNA) production following infection of Bacillus subtilis has been analyzed. Early (e) phi29 RNA, made prior to the onset of phage deoxyribonucleic acid (DNA) replication and exclusively from the light (L) phi29 DNA strand, has been shown by RNA-DNA hybridization-competition experiments to be present throughout the phage latent period. No repression of e RNA production during phi29 development could be demonstrated. Unmodified host RNA polymerase molecules appear to be sufficient for the synthesis of e RNA since phage-specific RNA made in the presence of chloramphenicol hybridizes only to the L strand of phi29 DNA, and this RNA can be effectively competed during hybridization by e RNA. The appearance of late (l) phi29 RNA is coincident with the onset of viral DNA replication. This RNA consists of L DNA strand transcripts which are identical to e RNA and a new class of mRNAs made exclusively from the "heavy" (H) phi29 DNA strand (lH). Protein synthesis in infected cells is required for lH RNA production. Studies with the antibiotic rifamycin demonstrated that synthesis of the major phi29 structural proteins is dependent on production of lH RNA.

Rifamycin-resistant mutation in E. coli: effect of rifamycin on DNA-dependent RNA polymerase and on R17 phage growth.

Rifamycin-resistant mutants in E. coli, K12, Hfr strain, were isolated without mutagenic treatment. The frequency of natural mutation of this type appeared to be approximately 10−9. Selection of resistant strains was effected by plating 109 cells on agar plates containing 50 μg of rifamycin per milliliter. A total of 11 strains resistant to rifamycin thus isolated remained Hfr and, in the presence of rifamycin, permitted the growth of the RNA-containing, male specific coliphage R17, which is sensitive to rifamycin in a wild-type E. coli. DNA-dependent RNA polymerase was prepared from these resistant mutants and examined for sensitivity toward rifamycin and other antibiotics. It was found that the RNA polymerase of the resistant strain is indeed resistant to rifamycin. However, both rifamycin-resistant and -sensitive enzymes are inhibited by the other three antibiotics (acridine orange, ethidium bromide, actinomycin D), which are known to interact with the template molecule.

The effects of the rifamycin antibiotics on algae

It is well known that blue-green algae and green algae clearly differ in their protein synthesis machinery, blue-green algae having 70 S ribosomes similar to those of bacteria in their sedimentation coefficient and sensitivity towards antibiotics [l-4] whereas the green algae cytoplasm contains 80 S ribosomes similar to other eukaryotic ribosomes in their sensitivity to antibiotics [l-7] . It appears that a similar situation might occur in the mechanism of RNA synthesis as it is widely accepted that the rifamycins are inhibitors of RNA polymerase from bacteria, mitochondria and chloroplasts but are not active on RNA polymerase from eukaryotic cells [8-141. We have studied the effects of the rifamycin antibiotics on a blue-green and a green algae and the results obtained are reported in this work.

Transient activation of RNA polymerase in Escherichia coli B after infection with bacteriophage T4.

Sköld and Buchanan(1) have reported that there is a rapid loss of RNA polymerase activity in Escherichia coli B after infection with T4 bacteriophage. More recent studies on the mechanism of this inactivation have been made in this(2) and other laboratories.(3, 4) In this communication, we report the observation of a transient stimulation of RNA polymerase activity when measurement is made immediately after infection and when cells are ruptured by a gentle lysis procedure. The increase in activity is independent of the synthesis of protein. The activity in the extracts of infected cells is lost by treatment of the extract with antibody to E. coli RNA polymerase and is refractive to the inhibitory action of the antibiotic rifamycin. Hybridization experiments indicate that an RNA transcribed almost exclusively from a T4 DNA template is the product of incubation of extracts of infected cells with a reaction mixture containing an exogenous primer (salmon sperm DNA). These findings are consistent with the hypothesis that one of the first steps in phage infection is the formation of a transcription complex containing T4 DNA and E. coli RNA polymerase.

Bacteriologic studies of rifampin, a new semisynthetic antibiotic.

Journal Article Bacteriologic Studies of Rifampin, a New Semisynthetic Antibiotic Get access Calvin M. Kunin, Calvin M. Kunin From the Departments of Preventive Medicine and Medicine, University of Virginia School of Medicine, Charlottesville, Virginia 22901* Search for other works by this author on: Oxford Academic PubMed Google Scholar David Brandt, David Brandt From the Departments of Preventive Medicine and Medicine, University of Virginia School of Medicine, Charlottesville, Virginia 22901* Search for other works by this author on: Oxford Academic PubMed Google Scholar Herbert Wood Herbert Wood From the Departments of Preventive Medicine and Medicine, University of Virginia School of Medicine, Charlottesville, Virginia 22901* Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Infectious Diseases, Volume 119, Issue 2, February 1969, Pages 132–137, https://doi.org/10.1093/infdis/119.2.132 Published: 01 February 1969 Article history Received: 29 July 1968 Published: 01 February 1969

The inhibition of bacterial RNA synthesis by the rifamycin antibiotics

The inhibition of bacterial RNA synthesis by the rifamycin antibiotics