The Journal of Antibiotics
Online ISSN : 1881-1469
Print ISSN : 0021-8820
ISSN-L : 0021-8820
Volume 56 , Issue 2
Showing 1-22 articles out of 22 articles from the selected issue
  • KIYOTAKA FUJINE, MIHO TANAKA, KEISUKE OHSUMI, MICHIZANE HASHIMOTO, SHI ...
    2003 Volume 56 Issue 2 Pages 55-61
    Published: February 25, 2003
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    Novel immunosuppressive agents, FR252921, FR252922 and FR256523 were isolated from the cultured broth of a bacterial strain No. 408813. The strain was identified Pseudomonas fluorescens from morphological and physiological characteristics.
    FR252921, FR252922 and FR256523, novel compounds containing macrolactone ring, showed immunosuppressive activity against murine splenocyte proliferation stimulated with lipopolysaccharide (LPS) or anti-CD3 mAb in vitro.
    Download PDF (1223K)
  • KIYOTAKA FUJINE, FUMIE ABE, NOBUO SEKI, HIROTSUGU UEDA, MOTOHIRO HINO, ...
    2003 Volume 56 Issue 2 Pages 62-67
    Published: February 25, 2003
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    A novel immunosuppressive agent, FR252921 was isolated from the cultured broth of a species of Pseudomonas fluorescens. We have shown that FR252921 inhibited splenic proliferation stimulated with LPS, insensitive to calcinuerin inhibitor. In this study, FR252921 was found to inhibit IL-2 and IL-12 production as well as proliferaion of splenocyte. Analysis of transcription activity revealed that FR252921 inhibited activating protein-1 (AP-1). Exposures of antigen presenting cells (APC) to FR252921 attenuated proliferation supplemented by naïve T cells. Further, FR252921 strongly suppressed splenic dendritic cell proliferation stimulated with LPS and anti-CD40 mAb, while it did not inhibit purified T cell activation, including CD154 expression and IL-2 production. These results suggest that APC is dominant target cell population.
    Download PDF (852K)
  • KIYOTAKA FUJINE, HIROTSUGU UEDA, MOTOHIRO HINO, TAKASHI FUJII
    2003 Volume 56 Issue 2 Pages 68-71
    Published: February 25, 2003
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    A novel immunosuppressive agent, FR252921 was isolated from the cultured broth of a species of Pseudomonas fluorescens. We have shown that FR252921 inhibit activating protein-1 (AP-1) transcription activity and act dominantly against antigen presenting cells comparing to T cell. Possibility of FR252921 as concomitant drug of FK506, T-cell specific inhibitor was evaluated. FR252921 showed synergy with FK506 in immunosuppressive activity both in splenic proliferation and in murine skin transplantation.
    Download PDF (485K)
  • HIROAKI MORI, YASUHARU URANO, FUMIE ABE, SATOKO FURUKAWA, SHIGETADA FU ...
    2003 Volume 56 Issue 2 Pages 72-79
    Published: February 25, 2003
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    A cyclic tetrapeptide FR235222, a novel immunosuppressant, has been isolated from the fermentation broth of a fungus, Acremonium sp. No. 27082. FR235222 showed potent and selective inhibitory effects on both T cell proliferation and lymphokine production. Further study has revealed this compound exhibits potent inhibitory effects on the activity of mammalian histone deacetylases (HDACs).
    Download PDF (1862K)
  • HIROAKI MORI, FUMIE ABE, SATOKO FURUKAWA, SHIGETADA FURUKAWA, FUMIHIKO ...
    2003 Volume 56 Issue 2 Pages 80-86
    Published: February 25, 2003
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    FR235222, a novel immunosuppressant which possesses potent inhibitory effects on the activity of mammalian histone deacetylases (HDACs), has been isolated from the fermentation broth of a fungus, Acremonium sp. No. 27082. FR235222 exhibited marked immunosuppressive effects on mouse ex vivo splenic T-lymphocyte proliferation, mouse delayed type hypersensitivity (DTH) response, rat adjuvant-induced arthritis (AA) and rat heterotopic cardiac transplantation. These results showed potential clinical use of this compound as a new type immunosuppressant in the fields of autoimmune diseases and organ transplantations.
    Download PDF (1072K)
  • JING CHEN, JIANBO WU, YUAN LI, RONG JIANG, BAOYI LI
    2003 Volume 56 Issue 2 Pages 87-90
    Published: February 25, 2003
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    Interleukin (IL)-1 is known to be a cytokine which plays a major role in pathological conditions like septic shock, inflammation and auto-immune disease, hence, methods that reduce the activity of IL-1 have an impact on clinical medicine. Inhibiting the binding of IL-1 to IL-1 receptors is one of the methods. A new inhibitor of IL-1 receptor, 139A, was isolated from the fermentation broth of Streptomyces sp. 139. It was extracted from the broth filtrate, purified by Diaion HP-20, cation exchange resin and DEAE Sephadex A-25. 139A was identified as polysaccharide, its structure was elucidated on the basis of spectral analysis, the immobilized ligand IL-1 receptor binding assay (IL-1LRBA) proved 139A can competitively inhibits the binding of IL-1 to IL-1 receptors.
    Download PDF (493K)
  • MICHAEL KURZ, CLAUDIA EDER, DIETER ISERT, ZIYU LI, ERICH F. PAULUS, MA ...
    2003 Volume 56 Issue 2 Pages 91-101
    Published: February 25, 2003
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    Ustilago species produce an extracellular oil that shows activity in various pharmaceutical assays. We isolated several complexes of this heterogeneous glycolipid from cultures of Ustilago maydis DSM 11494 and Geotrichum candidum ST 002515, and determined the chemical structures of these new compounds, termed ustilipids, on the basis of NMR experiments, mass spectra, and fatty acid analyses. They all possess a 4-O-β-D-mannopyranosyl D-erythritol basic framework, the configuration of which was confirmed, after initial solvolysis, by a single-crystal X-ray structure analysis. All the investigated ustilipids and related compounds are similarly constructed: the three hydroxy groups of the erythritol side chain are free in all cases, whereas the hydroxy groups of the mannose residue are for the most part acylated. Medium-chain fatty acids have for the first time been detected as components of glycolipids produced by Ustilaginales. While the 2-hydroxy group of the mannose residue is esterified with a C2-C8 carboxylate side chain, the 3-hydroxy group is in all cases esterified by a longer, C12-C20 fatty acid residue. The oxygen functionalities at the 4 and 6 positions are either acetylated or present as free hydroxy groups.
    Ustilipids antagonize dopamine D3 receptors in micromolar quantities; other members of this class of compounds have been found to possess an inhibitory action on the neurotensin receptor. The hemolytic activity of ustilipids is low.
    Download PDF (1481K)
  • HEE-GUK BYUN, HUIPING ZHANG, MASAMI MOCHIZUKI, KYOKO ADACHI, YOSHIKAZU ...
    2003 Volume 56 Issue 2 Pages 102-106
    Published: February 25, 2003
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    Marine fungi producing antifungal compounds were screened against Pyricularia oryzae (P. oryzae), and a metabolite of marine fungus M-3 isolated from laver (Porphyra yezoensis) showed potent activity. Novel diketopiperazine (1) was isolated from the culture extracts, and its structure was elucidated by spectroscopic methods. The MIC of 1 against P. oryzae was 0.36μM.
    Download PDF (602K)
  • YASUHIRO IGARASHI, KATSUYUKI FUTAMATA, TSUYOSHI FUJITA, AKIRA SEKINE, ...
    2003 Volume 56 Issue 2 Pages 107-113
    Published: February 25, 2003
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    In the screening of novel antifungal compounds, yatakemycin was found in the culture broth of Streptomyces sp. TP-A0356. Yatakemycin was obtained by solvent extraction of the fermentation broth and chromatographic purification using ODS column and preparative HPLC. The structure of yatakemycin was elucidated by NMR and CID-MS/MS experiments as a novel antibiotic belonging to a family of CC-1065 and duocarmycins known to be DNA alkylating agents. Yatakemycin inhibited the growth of pathogenic fungi such as Aspergillus fumigatus and Candida albicans with the MIC values of 0.01-0.03μg/ml, more potent than amphotericin B (MIC: 0.1-0.5μg/ml) or itraconazole (MIC: 0.03-0.2μg/ml). It also showed potent cytotoxicity against cancer cell lines with the IC50 of 0.01-0.3μg/ml.
    Download PDF (1348K)
  • MARIAN PAUL SEGETH, ALAIN BONNEFOY, MARK BRÖNSTRUP, MARTIN KNAUF, ...
    2003 Volume 56 Issue 2 Pages 114-122
    Published: February 25, 2003
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    The coprophilic ascomycete Coniochaeta ellipsoidea DSM 13856 forms the new antibiotic coniosetin (1) in surface cultures grown on a medium containing malt extract and oatmeal. The structure of the compound C25H35NO4, MW 413, was determined by 2D-NMR and mass spectrometric studies. Coniosetin belongs to the class of tetramic acids; it consists of a substituted aliphatic bicyclic ring system linked to a tetramic acid subunit through a carbonyl center. The absolute configuration was determined by measuring its circular dichroism spectrum and comparing the data with those of equisetin. Coniosetin has a pronounced antibacterial and antifungal action, inhibiting even multi drug-resistant strains of Staphylococcus aureus at a concentration of 0.3μg/ml, though it is inactive against Gramnegative bacteria.
    Download PDF (1253K)
  • KOJI NAGAI, KAZUMA KAMIGIRI, NAKAKO ARAO, KEN-ICHI SUZUMURA, YASUHIRO ...
    2003 Volume 56 Issue 2 Pages 123-128
    Published: February 25, 2003
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    Novel antibiotics, YM-266183 (1) and YM-266184 (2), were found in the culture broth of Bacillus cereus QN03323 which was isolated from the marine sponge Halichondria japonica. The structures of both antibiotics were determined by several spectroscopic experiments as new thiopeptide compounds. They exhibited potent antibacterial activities against staphylococci and enterococci including multiple drug resistant strains, whereas they were inactive against Gramnegative bacteria.
    Download PDF (1541K)
  • KEN-ICHI SUZUMURA, TAKAKO YOKOI, MASASHI FUNATSU, KOJI NAGAI, KOICHI T ...
    2003 Volume 56 Issue 2 Pages 129-134
    Published: February 25, 2003
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    YM-266183 and YM-266184 are new antibacterial substances that have activity against drug-resistant bacteria produced by Bacillus cereus QN03323. These structures were elucidated by MS and NMR spectral analysis. YM-266183 and YM-266184 are the cyclic thiopeptides containing thiazole and pyridine moieties, and several unusual amino acids.
    Download PDF (596K)
  • KARI-ANN DRAKER, DAVID D. BOEHR, NADINE H. ELOWE, THERESA J. NOGA, GER ...
    2003 Volume 56 Issue 2 Pages 135-142
    Published: February 25, 2003
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    The growing availability of sequences of bacterial genomes has revealed a number of open reading frames predicted by sequence alignment to encode antibiotic resistance proteins. The presence of these putative resistance genes within bacterial genomes raises important questions regarding potential reservoirs of resistance elements and their evolution. Here we examine four gene products encoding predicted aminoglycoside-aminocyclitol antibiotic modifying enzymes, two phosphotransferases and two acetyltransferases, derived from analysis of the genome sequence of Mycobacterium tuberculosis strain H37Rv with the goal of assigning biochemical function by purification of each protein and characterization of their ability to modify aminoglycoside antibiotics. Only one of these enzymes, the previously characterized aminoglycoside acetyltransferase AAC(2')-Ic, displayed compelling aminoglycoside modifying activity. While the putative phosphotransferase encoded by the Rv3225c gene did display low levels of aminoglycoside kinase activity, the predicted kinase encoded by the Rv3817 gene lacked any such activity. A potential aminoglycoside 6'-acetyltransferase, encoded by the Rv1347c gene, did not show antibiotic acylation activity but did demonstrate selective thioesterase activity with numerous acyl-CoAs. This activity, together with the genomic environment of the Rv1347c gene in a likely polyketide synthesis cluster, suggests a role for this protein in secondary metabolism and not in antibiotic modification. It was thus shown that only one of four putative aminoglycosides modifying enzymes derived from the whole genome sequencing of M. tuberculosis H37Rv showed sufficient predicted enzyme activity to be annotated as an aminoglycoside resistance element. This study demonstrates the necessity of biochemical annotation methods as a follow up to in silico sequence alignment-based methods of assigning gene product function.
    Download PDF (1913K)
  • ANNE HAUTALA, SIRKE TORKKELL, KAJ RÄTY, TERO KUNNARI, JAANA KANTO ...
    2003 Volume 56 Issue 2 Pages 143-153
    Published: February 25, 2003
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    This paper focuses on study of second and third ring cyclization in anthracycline biosynthesis by a heterologous gene expression. Firstly, anthracycline non-producing Streptomyces peucetius mutant, D2 was heterologously complemented to produce daunomycins with plasmids pSgs44 and pSYE66, which contain putative cyclase genes of S. galilaeus and S. nogalater, respectively. A point mutation in the cyclase gene dpsY of D2 has changed glycine to serine resulting inactivation of the enzyme. Secondly, the putative cyclase gene snoaM from S. nogalater, was expressed in a gene cassette in S. lividans TK24 and S. coelicolor CH999 to study the influence of the cyclase gene on auramycinone production and the impact of endogenous genes on production profiles. The results obtained confirms that a cyclase closing the second and third ring of a polyketide is essential in anthracycline biosynthesis.
    Download PDF (1413K)
  • RYOU HIBAYASHI, NOBUTAKA IMAMURA
    2003 Volume 56 Issue 2 Pages 154-159
    Published: February 25, 2003
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    Argimicin A is a potent anti-cyanobacterial compound produced by one of algae-lysing bacteria, Sphingomonas sp. M-17. Since the compound seemed to exhibit selective activities against cyanobacteria and such selectivity were considered to be quite rare, the mode of action of argimicin A was investigated. Argimicin A showed a unique delayed action, i.e., the cyanobacterial cell division continued until at least 36 hours treatment even though the decrement of oxygen evolution has been observed at 24 hours treatment. The compound is concluded to be a photosynthetic inhibitor which interrupts electron transport chain prior to photosystem II. From the preliminary fluorescent spectrum of argimicin A treated cyanobacterial cells, the site of action was speculated to be photo energy transfer from a cyanobacterial specific complex of accessory protein pigments, phycobilisome, to photosystem II.
    Download PDF (792K)
  • MYOUNG GOO KIM, ULRICH STRYCH, KURT KRAUSE, MICHAEL BENEDIK, HAROLD KO ...
    2003 Volume 56 Issue 2 Pages 160-168
    Published: February 25, 2003
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    A select series of N(2)-substituted D, L-cycloserine derivatives were prepared and evaluated for inhibitory activity against purified alanine racemases (alr gene product) from Escherichia coli, Staphylococcus aureus, and Mycobacterium tuberculosis, as well as in a growth inhibition assay. N(2)-Modification led to loss of enzymatic inhibitory activity in most cases consistent with a recent proposal for cycloserine function.
    Download PDF (1177K)
  • YASUAKI ESUMI, YOSHIKATSU SUZUKI, TERUO ICHIKAWA, YOSHIKAZU IKEDA, KEN ...
    2003 Volume 56 Issue 2 Pages 169-172
    Published: February 25, 2003
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    Download PDF (501K)
  • K. C. SEKHAR RAO, S. DIVAKAR, M. SRINIVAS, K. NAVEEN BABU, N. G. KARAN ...
    2003 Volume 56 Issue 2 Pages 173-176
    Published: February 25, 2003
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    Download PDF (511K)
  • YOUNG CHEOL KIM, HYO-JEONG KIM, KEUN-HYUNG PARK, JEUNG-YONG CHO, KIL-Y ...
    2003 Volume 56 Issue 2 Pages 177-180
    Published: February 25, 2003
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    Download PDF (492K)
  • HIROAKI MORI, YASUHARU URANO, TAKAYOSHI KINOSHITA, SEIJI YOSHIMURA, SH ...
    2003 Volume 56 Issue 2 Pages 181-185
    Published: February 25, 2003
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    Download PDF (514K)
  • SHU-WEI YANG, TZE-MING CHAN, SHIRLEY A. POMPONI, GUODONG CHEN, DAVID L ...
    2003 Volume 56 Issue 2 Pages 186-189
    Published: February 25, 2003
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    Download PDF (354K)
  • Japanese Society of Antimicrobials for Animals, TSUGIAKI FUKUYASU, SH ...
    2003 Volume 56 Issue 2 Pages 190-196
    Published: February 25, 2003
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    In view of the recent rapid increase in incidence of infection with antimicrobial resistant bacteria in human medicine, there is international controversy as to the medical risk that is created by transfer of antimicrobial resistant bacteria and antimicrobial resistant genes, which may be produced through the processes of administration of antimicrobials to food-producing animals, via the food chain. Accordingly, International Cooperation on Harmonization of Technical Requirements for Registration of Veterinary Medicinal Products (VICH) provides the comprehensive guidelines for characterizing selection of antimicrobial resistance by bacteria which may adversely affect human health in order to establish the system of registry of antimicrobial drugs to be administered to food-producing animals.
    Currently, Japanese Society of Antimicrobials for Animals recognizes the lack of technical test standards in compliance with VICH guidelines in the world and has established the test standards for "in vitro mutation frequency studies" to evaluate the appearance frequency and resistant level of resistant bacteria and those for studies on the "antimicrobial activity in gut" to estimate the effects on intestinal flora from professional aspects.
    Download PDF (1104K)
feedback
Top