ANTIMICROBIAL AGENTS and CHEMOTHERAPY VOLUME 25 * JUNE 1984 NUMBER 6 Leon H

Total Page:16

File Type:pdf, Size:1020Kb

ANTIMICROBIAL AGENTS and CHEMOTHERAPY VOLUME 25 * JUNE 1984 NUMBER 6 Leon H ANTIMICROBIAL AGENTS AND CHEMOTHERAPY VOLUME 25 * JUNE 1984 NUMBER 6 Leon H. Schmidt, Editor in Chief (1985) George A. Jacoby, Jr., Editor (1985) University ofAlabama in Birmingham Massachusetts General Hospital Birmingham Boston Herbert L. Ennis, Editor (1987) Robert C. Moellering, Jr., Editor (1987) Roche Institute ofMolecular Biology New England Deaconess Hospital Nutley, New Jersey Boston, Massachusetts Robert L. Hamill, Editor (1985) John A. Washington II, Editor (1986) Eli Lilly & Company, Inc. Mayo Clinic Indianapolis, Indiana Rochester, Minnesota Peter G. Welling, Editor (1988) Warner-Lambert Co. Ann Arbor, Michigan EDITORIAL BOARD Norris Allen (1986) Robert J. Fass (1985) Stuart B. Vincent T. Andriole (1984) Stuart Feldman Levy (1986) Merle Sande (1985) John P. Anhalt (1984) (1985) Friedrich C. Luft (1984) Christine C. Sanders (1984) Bascom F. Anthony (1985) Sydney Finegold (1985) Joan Lusk (1986) W. Eugene Sanders (1984) Robert J. Fitzgerald (1986) R. Luthy (1986) W. Michael George R. Aronoff (1986) Martin Forbes (1986) Francis L. Scheld (1986) Robert Austrian (1986) Dale Macrina (1985) Jerome J. Schentag (1985) Richard N. Gerding (1985) Gerald L. (1986) Raymond F. Schinazi H. Baltz (1984) David Gilbert (1984) R. MatzkeMandell (1986) Rashmi H. Barbhaiya (1986) J. Glazko Gary (1986) Fritz D. Schoenknecht (1986) Arthur L. Barry (1986) Anthony (1984) George H. McCracken (1984) F. C. Sciavolino (1985) Irving H. Goldberg (1985) Gerald Medoff (1986) William John D. Bartlett (1984) Richard H. Gustafson (1984) Michael M. Shannon (1986) Michael Barza (1985) Jack Miller (1984) Charles Shipman, Jr. (1985) John E. Bennett (1984) Gwaltney (1986) Barbara Minshew (1985) Robert W. Sidwell (1984) Scott M. Hammer (1986) Bernard Moss (1984) P. Frederick Richard F. Bergstrom (1985) W. Lee Hand (1986) Thomas P. Sparling (1984) Gerald P. Bodey (1986) H. Hunter Moyer (1986) Harold Standiford (1985) Lawrence E. Bryan (1985) Handsfield (1986) Barbara E. Murray (1984) David A. Stevens (1986) Maurice W. Harmon (1984) John D. Nelson (1986) R. Sutherland Ward Bullock (1984) Joseph Hawkins, Jr. (1985) Harold C. (1985) Tsun Chang (1986) Michael Neu (1986) Vera L. Sutter (1984) Anthony Chow (1985) Higgins (1986) James T. Park (1985) Morton N. Swartz (1985) C. Richard Hornick (1986) James E. Pennington (1986) Richard B. Sykes Glenn Cobbs (1986) George Gee Jackson (1986) T. J. Perun (1985) Paul S. Cohen (1986) James H. (1986) Francis P. Tally (1984) William A. Jorgensen (1984) Lance R. Peterson (1985) Alexander Tomasz Craig (1984) William J. Jusko (1986) Burton M. Pogell (1984) (1985) Naomi Datta (1984) A. W. Karchmer (1985) Michael Ralph Tompsett (1985) Lawrence E. Day (1986) Donald Rein (1986) Francis L. S. Tse (1986) William E. Dismukes (1984) Kaye (1985) W. H. G. Richards (1986) Michael Waring (1984) R. George S. Kobayashi (1985) Richard Roberts (1985) Bernard Gordon Douglas, Jr. (1986) Donald J. Krogstad (1986) Ian M. Weisbium (1985) John C. Drach (1984) Felix Rollo (1985) Richard M. Welch (1986) Theodore Leitner (1986) Richard Root (1986) Richard Wise Eickhoff (1985) Stephen A. Lerner (1986) John P. Rosazza (1986) Gertrude B. Elion (1984) Matthew E. Levison (1986) Lowell Young (1985) Arthur English (1986) (1984) Jon E. Rosenblatt (1985) Pauline K. W. Yu (1985) Helen R. Whiteley, Chairman, Publications Board Walter G. Linda M. Illig, Peter III, Director ofPublications Managing Editor, Journals Deborah J. Shuman, Production Editor Antimicrobial Agents and Chemotherapy (ISSN 1913 I St., NW, 0066-4804), an interdisciplinary publication of the American Society for Microbiology, Washington, DC 20006, is devoted to the dissemination of knowledge relating to all aspects of anticancer agents and chemotherapy. Instructions to authors are published in antimicrobial, antiparasitic, and editors and the Publications Department. the January issue each year; reprints are available from the into two Antimicrobial Agents and Chemotherapy is published monthly, and the twelve numbers are volumes per year. The nonmember subscription price is $157 per year; single copies are divided (foreign, $41 [surface rate]) per year; single copies are $7. $21. The member subscription price is $31 back issues, lost or late Correspondence relating to subscriptions, reprints, defective copies, availability of proofs, disposition of submitted manuscripts, and general editorial matters should be Department, 1913 I St., NW, Washington, DC 20006 (phone: 202 833-9680). directed to the ASM Publications Claims for missing issues from residents of the United States, Canada, and Mexico the issues; residents of all other countries must submit must be submitted within 3 months after publication of of failure to claims within 6 months of publication of the issues. Claims for issues missing report an address change or for issues "missing from files" will not be allowed. because Second-class postage paid at Washington, DC 20006, and at additional mailing offices. POSTMASTER: Send address changes to Antimicrobial Agents and Made in the United States of America. Chemotherapy, ASM, 1913 I St.. NW, Washington, DC 20006. Copyright © 1984, American Society for ii All Rights Reserved. Microbiology. H*: 14ltS* e ;11wl* ( Fl4u. The code at the top of the first page of an made for article in this journal indicates the copyright owner's consent that copies of the article personal use or for personal use of specific clients. This consent is given on the condition, may be per-copy fee through the Copyright Clearance Center, Inc., 21 however, that the copier pay the stated 107 and 108 of the U.S. Copyright Congress St., Salem, MA 01970, for copying beyond that permitted by Sections Law. This consent does not extend to other kinds of copying, such as copying for general advertising or promotional purposes, for creating new collective works, or for resale. distribution, for Author Index Ackerman, Bruce H., 785 Gotoh, Akira, 754 Malewicz, B., 772 Stachowski, Michael, 778 Actor, Paul, 694 Grappel, Sarah F., 694 Momsen, M., 772 Strikas, Raymond, 778 Apolloni, E., 760 Grossman, Dena M., 690 Morrison, Joan O., 725 Sun, Chong-Son, 729 Arosio, E., 760 Guymon, L. F., 767 Myers, William F., 690 Tannenbaum, Charles S., 673 Baron, Ellen J., 781 Hastie, Annette T., 673 Neu, Harold C., 687 Thornsberry, Clyde, 710 Barry, Arthur L., 710, 775 Higgins, Michael L., 673 Neut, C., 764 Tofte, Robert W., 785 Bayer, Arnold S., 725 Hindler, Janet A., 781 Bedows, Elliott, 719 Benoni, G., 760 Jakas, Dalia R., 694 Parr, Thomas R., Jr., 747 Ubukata, Kimiko, 754 Borowski, E., 772 James, Philip R., 735 Parrillo, Patricia, 778 Bryan, L. E., 747 Jenkin, H. M., 772 Passarella, E., 760 Vaara, M., 701 Jones, Ronald N., 710, 775 Penn, Robert L., 770 Velo, G. P., 760 Campos, Jose, 706 Phillips, Lillian, 694 Verbist, Ludo, 783 Catlin, B. Wesley, 676 King, John W., 770 Pitkin, Donald, 694 Verpooten, Gert A., 783 Chin, Nai-Xun, 687 Knight, Paul R., 719 Pollet, Dirk E., 783 Viljarten, P., 701 Knight, Vernon, 729 Vosbeck, Klaus, 735 Davidson, Bruce A., 719 Kobasa, William D., 683 Raimondi, M. G., 760 Romond, C., 764 De Broe, Marc E., 783 Konno, Masatoshi, 754 Weinbaum, George, 673 Devos, J., 764 Kramer, Michael J., 729 Ross, Janette, 785 Rotschafer, John C., 785 Wilson, Samuel Z., 729 Dubreuil, L., 764 Kueppers, Friedrich, 673 Wisseman, Charles L., Jr., 690 Dunn, George L., 694 Wyde, Philip R., 729 Labthavikul, Pornpen, 687 Sakuma, Takashi, 742 Eisenstadt, Rosalee, 725 Lechi, A., 760 Sanfeliu, Isabel, 706 Lentino, Joseph R., 778 Scharpe, Simon L., 783 Yamashita, Naoko, 754 Garcia-Tornel, Santiago, 706 Levison, Matthew E., 683 Shafer, W. M., 767 Giuliano, Ruben A., 783 Lind, I., 767 Sparling, P. F., 767 Zimmermann, Willy, 735 AUTHOR INDEX VOLUME 25 Ackerman, Bruce H., 785 Bongaerts, Ger P. A., 234 Dotzlaf, Joe E., 216 Glasser, Lynne A., 510 Ackers, Irene, 579 Borner, K., 105 Dromer, Francoise, 168 Glette, Johan, 354 Actor, P., 373 Borobio, M. Victoria, 342 Dubois, Catherine, 168 Gnarpe, H'akan, 179 Actor, Paul, 694 Borowski, E., 772 Dubreuil, L., 764 Godefroy, Isabelle, 168 Adejuyigbe, Olusanya, 497 Borsa, F., 638 Dunn, George L., 694 Godfrey, A. J., 382 Adkinson, N. Franklin, Jr., 93 Bosso, John A., 630 Dworzack, David L., 494 Goessens, Wil H. F., 575 Ahmed, S. Masud, 643 Boutwell, M. E., 650 Dylewski, Joe S., 25 Goldman, Peter, 65 Akhter, S. Q., 643 Bouzos, John, 534 Gombert, Myles E., 510 Albritton, William L., 187, 296 Bright, Gene M., 113 East, Donald S., 83 Gooch, W. Manford, III, 502 Alford, Robert H., 405 Brion, Nils, 168 Eby, George A., 20 Goodman, Larry J., 504 Anderson, Burt, 296 Brook, Itzhak, 71 Echols, Roger M., 336 Gootz, Thomas D., 591 Andreana, Augusto, 182 Brown, Daniel R., 422 Egbert, Peter R., 25 Gordon, Y. Jerold, 522 Andrews, J. M., 612 Brown, Douglas, 286 Eisenstadt, Rosalee, 725 Goto, Sachiko, 98 Andritz, Mary H., 33 Brown, Timothy H., 405 Elion, Gertrude B., 507 Gotoh, Akira, 754 Angehrn, Peter, 607 Brumfitt, W., 276 Eliopoulos, G. M., 331, 401 Goueffon, Y., 463 Apolloni, E., 760 Bryan, C. S., 37 Eliopoulos, George M., 398 Grappel, Sarah F., 694 Arbeter, A. M., 417 Bryan, L. E., 382, 747 Elvers, A., 105 Greenman, Richard L., 16 Arceneaux, Jean E. L., 650 Buesing, Mary A., 283 Ene, Mokelu D., 1 Griffin, Paul E., 33 Arcey, Sergio M., 16 Butler, Thomas, 643 Eng, Robert H. K., 510 Gropen, Toby I., 522 Arndt, Kenneth A., 553 Buu-Hoi, Annie, 289 English, A. R., 118 Grossman, Dena M., 690 Aronoff, George R., 513 Byers, B. R., 650 English, Arthur R., 113, 226, 599 Gruft, Howard, 137 Aronoff, Stephen C., 279 Eppstein, Deborah A., 563 Guay, David R., 306 Arosio, E., 760 Cabezudo, Ignacio, 4 Guenthner, Sharon H., 4 Asahi, Yoshinari, 131 Cable, Douglas C., 258 Fadl-Allah, Nora, 375 Guerrant, Richard L., 653 Ash, Ronald J., 443 Campbell, Gwendolyn S., 205 Fainstein, V., 387 Gutterman, Deborah A., 16 Assael, Baroukh M., 395 Campos, Jose, 706 Falkinham, Joseph O., III, 137 Guymon, L.
Recommended publications
  • WO 2018/005606 Al 04 January 2018 (04.01.2018) W !P O PCT
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2018/005606 Al 04 January 2018 (04.01.2018) W !P O PCT (51) International Patent Classification: KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, A61K 38/43 (2006.01) A61K 47/36 (2006.01) MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, A61K 38/50 (2006.01) A61K 9/S0 (2006.01) OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, A61K 33/44 {2006.01) SC, SD, SE, SG, SK, SL, SM, ST, SV, SY,TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (21) International Application Number: PCT/US20 17/039672 (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (22) International Filing Date: GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, 28 June 2017 (28.06.2017) UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, (25) Filing Language: English TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, (26) Publication Langi English MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, (30) Priority Data: TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, 62/355,599 28 June 2016 (28.06.2016) US KM, ML, MR, NE, SN, TD, TG).
    [Show full text]
  • Drug Allergies: an Epidemic of Over-Diagnosis
    Drug Allergies: An Epidemic of Over-diagnosis Donald D. Stevenson MD Senior Consultant Div of Allergy, Asthma and Immunology Scripps Clinic Learning objectives • Classification of drug induced adverse reactions vs hypersensitivity reactions • Patient reports of drug induced reactions grossly overstate the true prevalence • The 2 most commonly recorded drug “allergies”: NSAIDs and Penicillin • Accurate diagnoses of drug allergies • Consequences of falsely identifying a drug as causing allergic reactions Classification of Drug Associated Events • Type A: Events occur in most normal humans, given sufficient dose and duration of therapy (85-90%) – Overdose Barbiturates, morphine, cocaine, Tylenol – Side effects ASA in high enough doses induces tinnitus – Indirect effects Alteration of microbiota (antibiotics) – Drug interactions Increased blood levels digoxin (Erythromycin) • Type B: Drug reactions are restricted to a small subset of the general population (10-15%) where patients respond abnormally to pharmacologic doses of the drug – Intolerance: Gastritis sometimes bleeding from NSAIDs – Hypersensitivity: Non-immune mediated (NSAIDs, RCM) – Hypersensitivity: Immune mediated (NSAIDs, Penicillins ) Celik G, Pichler WJ, Adkinson Jr NF Drug Allergy Chap 68 Middleton’s Allergy: Principles and Practice, 7th Ed, Elsevier Inc. 2009; pg 1206 1206. Immunopathologic (Allergic) reactions to drugs (antigens): Sensitization followed by re-exposure to same drug antigen triggering reaction Type I Immediate Hypersensitivity IgE Mediated Skin testing followed
    [Show full text]
  • Anew Drug Design Strategy in the Liht of Molecular Hybridization Concept
    www.ijcrt.org © 2020 IJCRT | Volume 8, Issue 12 December 2020 | ISSN: 2320-2882 “Drug Design strategy and chemical process maximization in the light of Molecular Hybridization Concept.” Subhasis Basu, Ph D Registration No: VB 1198 of 2018-2019. Department Of Chemistry, Visva-Bharati University A Draft Thesis is submitted for the partial fulfilment of PhD in Chemistry Thesis/Degree proceeding. DECLARATION I Certify that a. The Work contained in this thesis is original and has been done by me under the guidance of my supervisor. b. The work has not been submitted to any other Institute for any degree or diploma. c. I have followed the guidelines provided by the Institute in preparing the thesis. d. I have conformed to the norms and guidelines given in the Ethical Code of Conduct of the Institute. e. Whenever I have used materials (data, theoretical analysis, figures and text) from other sources, I have given due credit to them by citing them in the text of the thesis and giving their details in the references. Further, I have taken permission from the copyright owners of the sources, whenever necessary. IJCRT2012039 International Journal of Creative Research Thoughts (IJCRT) www.ijcrt.org 284 www.ijcrt.org © 2020 IJCRT | Volume 8, Issue 12 December 2020 | ISSN: 2320-2882 f. Whenever I have quoted written materials from other sources I have put them under quotation marks and given due credit to the sources by citing them and giving required details in the references. (Subhasis Basu) ACKNOWLEDGEMENT This preface is to extend an appreciation to all those individuals who with their generous co- operation guided us in every aspect to make this design and drawing successful.
    [Show full text]
  • Thienamycin**, a /3-Lactam Antibiotic with the Unique Structure Shown in Fig
    THIENAMYCIN, A NEW 8-LACTAM ANTIBIOTIC 1. DISCOVERY, TAXONOMY, ISOLATION AND PHYSICAL PROPERTIES* J. S. KAHAN, F. M. KAHAN, R. GOEGELMAN, S. A. CURRIE, M. JACKSON, E. O. STAPLEY, T. W. MILLER, A. K. MILLER, D. HENDLIN, S. MOCHALESt, S. HERNANDEZt, H. B. WOODRUFF and J. BIRNBAUM Merck Institute for Therapeutic Research, Mcrck Sharp & Dohme Research Laboratories Rahway, New Jersey, U.S.A. 07065 tCompania Espanola de ]a Penicilina y Antibioticos S. A., Madrid, Spain (Received for publication September 5, 1978) A new //-lactam antibiotic, named thienamycin, was discovered in culture broths of Streptomyces MA4297. The producing organism, subsequently determined to be a hitherto unrecognized species, is designated Streptomyces cattleya (NRRL 8057). The antibiotic was isolated by adsorption on Dowex 50, passage through Dowex 1, further chromatography on Dowex 50 and Bio-Gel P2, and final purification and desalting on XAD-2. Thienamycin is zwitterionic, has the elemental composition CuHIGN2O4S(M.W.=272.18) and possesses a distinctive UV absorption (Amax=297 nm, e=7,900). Its /3-lactam is unusually sensitive to hydrolysis above pH 8 and to reaction with nucleophiles such as hydroxylamine, cysteine and, to a lesser degree, the primary amine of the antibiotic itself. The latter reaction results in accelerated inactivation at high antibiotic concentrations. Thienamycin**, a /3-lactam antibiotic with the unique structure shown in Fig. 11,2) was dis- covered in the course of screening soil microorganisms for production of inhibitors of peptidoglycan synthesisin Gram-positive and Gram-negative bacteria. Taxonomic studies of the producing organism MA4297 resulted in its assignment to a new streptomycete species which has been named Strepto- myces cattleya.
    [Show full text]
  • By Nicole M. Gaudelli
    MECHANISTIC AND STRUCTURAL STUDIES OF THE THIOESTERASE DOMAIN IN THE TERMINATION MODULE OF THE NOCARDICIN NRPS By Nicole M. Gaudelli A dissertation submitted to The Johns Hopkins University in conformity with the requirements for the degree of Doctor of Philosophy Baltimore, MD 2013 © Nicole M. Gaudelli 2013 All Rights Reserved Abstract The nocardicins are monocyclic -lactam antibiotics produced by the actinomycete Nocardia uniformis subsp., tsuyamanensis ATCC 21806. In 2004 the gene cluster responsible for the biosynthesis of the flagship antibiotic, nocardicin A, was identified. This gene cluster accommodates a pair of non- ribosomal peptide synthetase (NRPS) whose five modules are indispensible for antibiotic production. In accordance with the prevailing co-linearity model of NRPS function, a linear L,L,D,L,L pentapeptide was predicted to be synthesized. Contrary to expectation and precedent, however, a stereodefined series of synthesized potential peptide substrates for the nocardicin thioesterase (NocTE) domain failed to undergo hydrolysis. The stringent discrimination against peptide intermediates was dramatically overcome by prior monocyclic -lactam formation at an L-seryl site to render now facile substrates for C-terminal epimerization and hydrolytic release. It was concluded through biochemical and kinetic experimentation that the TE domain acts as a gatekeeper to hold the assembling peptide on an upstream domain until -lactam formation takes place and then rapidly catalyzes epimerization and hydrolysis to discharge a fully-fledged pentapeptide -lactam harboring nocardicin G, the simplest member of the nocardicin family. An x-ray crystal structure of the TE domain revealed a catalytic center containing the expected Asp, His, Ser triad. Mutational analysis of these catalytic residues along with a proximal His established that the His of the catalytic triad was likely responsible for the epimerization activity rendered by the domain.
    [Show full text]
  • Antibiotic Resistance Gene Resource and Assay List
    TechnicalInformation Antibiotic Resistance Gene Resource and Assay List Understanding the relationships between drugs and the genes that pathogens use to evade or neutralize them is imperative for successfully treating a range of infectious diseases. This resource provides an overview of these relationships and information about Microbial DNA qPCR Assays and Assay Kits, which specifically detect microbial antibiotic resistance genes. Overview Resistance to drugs that target pathogens is a serious public health concern. Resistance is the result of specific genes harbored by microorganisms that reduce the impact of drug molecules. Mechanisms employed by these gene products include covalent modification of the drug or target, removal of the drug from the cells, or activation of an alternative pathway. To understand an organism’s reaction to a drug or family of drugs, researchers must know which genes act on which set of drug compounds. Scientists can detect the presence of a specific antibiotic resistance gene in a sample by using QIAGEN’s Microbial DNA qPCR Assays and Assay Kits. These assays are highly sensitive and specific molecular analysis research tools, designed by a proprietary algorithm to test for the presence of microbial genes. The Microbial DNA qPCR Assays are a mix of two PCR primers and one 5′-hydrolysis probe that enables quantitative real-time PCR. They can screen for extremely small amounts of a target DNA sequence within a metagenomic sample. Microbial DNA qPCR Assay Kits (BBXX#####A) are a complete solution for real-time PCR-based microbial detection. Microbial DNA qPCR Assay Kits contain a Microbial DNA qPCR Assay, Microbial DNA Positive Control, Positive PCR Control, Microbial DNA-Free Water, and Microbial qPCR Mastermix — everything required for a successful qPCR run.
    [Show full text]
  • NOCARDICIN A, a NEW MONOCYCLIC P-LACTAM ANTIBIOTIC I
    492 THE JOURNAL OF ANTIBIOTICS MAY 1976 NOCARDICIN A, A NEW MONOCYCLIC p-LACTAM ANTIBIOTIC I. DISCOVERY, ISOLATION AND CHARACTERIZATION HATSUOAOKI, HEI-ICHI SAKAI*, MASANOBU KOHSAKA, TOSHIO KONOMI, JUNJIHOSODA, YOSHIAKI Kunocnl**, EIKOIGUCHI and HIROSHIIMANAKA ResearchLaboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka,Japan (Receivedfor publicationJanuary 12, 1976) NocardicinA is a new monocyclic,3-lactam antibiotic obtainedfrom the fermentation broth of a strain of actinomycetes. The producingorganism, strain WS 1571,was identified as Nocardia uniformissubsp. tsuyamanensisATCC 21806. The antibiotic, obtained as colorlesscrystals, exhibits moderate in vitro antibacterialactivity against a broad-spectrum of Gram-negativebacteria including Proteus and Pseudomonas.It has low toxicity in laboratoryanimals. In the course of an investigation directed toward the discovery of new and novel Q-lactam antibiotics, an actinomycete, designated strain WS 1571, was isolated from a soil sample collected in Tsuyama city, Okayama Prefecture, Japan. Shake flask cultures possessed stronger inhibitory activity on a mutant strain of Eschericlua coli which is specifically supersensitive to ~-lactam antibiotics than on the parent strain (Table 1). Its selective inhibitory activity on (3-lactam antibiotic supersensitive cells, together with its sensitivity to some 3-lactamases, made us presume that it was a ~-lactam antibiotic. An isolation program was therefore undertaken to obtain Fig. 1. Chemical structure of nocardicin A and other /3-lactam antibiotics. Table 1. Sensitivity of a mutant of Escherichia coli which is supersensitive to ,5-lactam antibio- tics. MIC (mcg/ml)* Antibiotic E. coli Es-11 (parent strain) (mutant strain) Nocardicin A Penicillin G 100 0.8 Cephalosporin C 400 0.4 Cephamycin C 100 1.6 Nocardicin A 400 0.4 Fosfomycin 1.6 1.6 Cephalosporin C Cycloserine 25 25 Kanamycin 6.3 6.3 Actinomycin C > 100 > 100 * MIC was determined by serial agar dilution method with heart infusion medium.
    [Show full text]
  • Antibiotics/Antibacterial Drug Use, Their Marketing and Promotion During the Post-Antibiotic Golden Age and Their Role in Emergence of Bacterial Resistance
    Vol.6, No.5, 410-425 (2014) Health http://dx.doi.org/10.4236/health.2014.65059 Antibiotics/antibacterial drug use, their marketing and promotion during the post-antibiotic golden age and their role in emergence of bacterial resistance Godfrey S. Bbosa1,2, Norah Mwebaza1, John Odda1, David B. Kyegombe3, Muhammad Ntale1,4 1Department of Pharmacology and Therapeutics, Makerere University College of Health Sciences, Kampala, Uganda; Email: [email protected] 2Department of Primary Care and Population Sciences, University of London, London, UK 3Department of Chemistry, Makerere University, College of Natural Sciences, Kampala, Uganda 4Kampala International University School of Health Sciences, Ishaka Campus, Busyenyi, Uganda Received 20 December 2013; revised 7 January 2014; accepted 4 February 2014 Copyright © 2014 Godfrey S. Bbosa et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In accor- dance of the Creative Commons Attribution License all Copyrights © 2014 are reserved for SCIRP and the owner of the intellectual property Godfrey S. Bbosa et al. All Copyright © 2014 are guarded by law and by SCIRP as a guardian. ABSTRACT rial disease burden and hence a significant glo- bal public health problem. The resistant bacterial During the post-antibiotic golden age, it has diseases lead to the high cost, increased occur- seen a massive antibiotic/antibacterial produc- rence of adverse drug reactions, prolonged hos- tion and an increase in irrational use of these pitalization, the exposure to the second- and few existing drugs in the medical and veterinary third-line drugs like in MDR-TB and XDR-TB that practice, food industries, tissue cultures, agri- leads to toxicity and deaths as well as the in- culture and commercial ethanol production creased poor production in agriculture and ani- globally.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2015/0150995 A1 Taft, III Et Al
    US 2015O150995A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2015/0150995 A1 Taft, III et al. (43) Pub. Date: Jun. 4, 2015 (54) CONJUGATED ANTI-MICROBIAL Publication Classification COMPOUNDS AND CONUGATED ANT-CANCER COMPOUNDS AND USES (51) Int. Cl. THEREOF A647/48 (2006.01) A63/546 (2006.01) (71) Applicant: PONO CORPORATION, Honolulu, HI A633/38 (2006.01) (US) (52) U.S. Cl. CPC ........... A61K47/480.15 (2013.01); A61K33/38 (72) Inventors: Karl Milton Taft, III, Honolulu, HI (2013.01); A61 K3I/546 (2013.01) (US); Jarred Roy Engelking, Honolulu, HI (US) (57) ABSTRACT (73) Assignee: PONO CORPORATION, Honolulu, HI Disclosed herein are synthesis methods for generation of (US) conjugated anti-microbial compounds and conjugated anti cancer compounds. Several embodiments, related to the uses (21) Appl.ppl. NNo.: 14/418,9079 of Such compoundsp in the treatment of infections, in particu lar those caused by drug-resistant bacteria. Some embodi (22) PCT Filed: Aug. 9, 2013 ments relate to targeting cancer based on the metabolic sig (86). PCT No.: PCT/US2O13/O54391 nature of tumor cells. S371 (c)(1), (2) Date: Jan. 30, 2015 NH Related U.S. Application Data O Ag" (60) Provisional application No. 61/742,443, filed on Aug. B-Lactam Silver Ion 9, 2012, provisional application No. 61/742,444, filed on Aug. 9, 2012. O O O O O O HSONaNO -pE (CHO)2SO2 OEt Br2 OEt 2W4 OH NOMe 1 2 3 Q Q H.N.S NH, NHT chicci -VV653C(CH) NaOH Bra-oe 2 2 S1N (C6H5)3C- SNN a NOMe MeO -co.
    [Show full text]
  • Isoxazole Beta-Lactamase Inhibitors Isoxazol-Beta-Lactamase-Hemmer Inhibiteurs Des Beta-Lactamases Dérivés D’Isoxazole
    (19) TZZ ¥_Z_T (11) EP 2 831 069 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: C07D 451/06 (2006.01) A61K 31/46 (2006.01) 12.07.2017 Bulletin 2017/28 A61P 31/00 (2006.01) C07D 471/08 (2006.01) A61K 45/06 (2006.01) A61K 31/407 (2006.01) (2006.01) (2006.01) (21) Application number: 13769389.1 A61K 31/427 A61K 31/546 (22) Date of filing: 29.03.2013 (86) International application number: PCT/US2013/034589 (87) International publication number: WO 2013/149136 (03.10.2013 Gazette 2013/40) (54) ISOXAZOLE BETA-LACTAMASE INHIBITORS ISOXAZOL-BETA-LACTAMASE-HEMMER INHIBITEURS DES BETA-LACTAMASES DÉRIVÉS D’ISOXAZOLE (84) Designated Contracting States: • ALEXANDER, Dylan, C. AL AT BE BG CH CY CZ DE DK EE ES FI FR GB Watertown, MA 02472 (US) GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO • CROSS, Jason, B. PL PT RO RS SE SI SK SM TR Acton, MA 01718 (US) Designated Extension States: • METCALF, Chester, A., III. BA ME Needham, MA 02492 (US) • BUSCH, Robert (30) Priority: 30.03.2012 US 201261618127 P Wakefield, MA 01880 (US) 15.03.2013 US 201361790248 P (74) Representative: Böhles, Elena et al (43) Date of publication of application: Merck Sharp & Dohme Limited 04.02.2015 Bulletin 2015/06 Hertford Road Hoddesdon, Herts EN11 9BU (GB) (73) Proprietor: Merck Sharp & Dohme Corp. Rahway, NJ 07065 (US) (56) References cited: WO-A1-2009/133442 WO-A1-2010/038115 (72) Inventors: KR-A- 20100 130 176 •GU,Yu Gui Acton, MA 01720 (US) • IAN K.
    [Show full text]
  • Gene Clusters for Β-Lactam Antibiotics and Control of Their Expression
    RESEARCH REVIEW INTERNATIONAL MICROBIOLOGY (2006) 9:9-19 www.im.microbios.org Paloma Liras Gene clusters for β-lactam Juan F. Martín* antibiotics and control of Biotechnological Institute, their expression: why have Scientific Park of Leon, Spain, and Microbiology Area, clusters evolved, and from Faculty of Biological where did they originate? and Environmental Sciences, University of Leon, Spain Summary. While β-lactam compounds were discovered in filamentous fungi, actinomycetes and gram-negative bacteria are also known to produce different types of β-lactams. All β-lactam compounds contain a four-membered β-lactam ring. The structure of their second ring allows these compounds to be classified into peni- cillins, cephalosporins, clavams, carbapenens or monobactams. Most β-lactams inhibits bacterial cell wall biosynthesis but others behave as β-lactamase inhibitors (e.g., clavu- lanic acid) and even as antifungal agents (e.g., some clavams). Due to the nature of the second ring in β-lactam molecules, the precursors and biosynthetic pathways of cla- vams, carbapenems and monobactams differ from those of penicillins and cephalospo- rins. These last two groups, including cephamycins and cephabacins, are formed from three precursor amino acids that are linked into the α-aminoadipyl-L-cysteinyl-D-valine tripeptide. The first two steps of their biosynthetic pathways are common. The interme- diates of these pathways, the characteristics of the enzymes involved, the lack of introns in the genes and bioinformatic analysis suggest that all of them should have evolved from an ancestral gene cluster of bacterial origin, which was surely transferred horizon- tally in the soil from producer to non-producer microorganisms.
    [Show full text]
  • Substance Index for Volume 66
    The Journal of Antibiotics (2013) 66, 749–753 & 2013 Japan Antibiotics Research Association All rights reserved 0021-8820/13 www.nature.com/ja Substance Index for Volume 66 (3R,4R)-4-Acetoxy-3-[(R)-1-(t-butyldimethylsilyloxy) 161 A26771B 123 ethyl]-2-azetidinone AB3217-A 123 4-O-(400-O-Acetyl-a-L-rhamnopyranosyl)-ellagic acid 123 Acidomycin 371 Bedaquiline 571 Aclacinomycin A, N-benzyl- 165 4-O-Benzoyl-2,3,6-trideoxy-3-C-methyl-3- 131 Actinopyrone A 123 trifluoroacetamido-a,b-L-lyxo-hexopyranosyl acetate Actinorhodin 387 4-O-Benzyl-2,3,6-trideoxy-3-C-methyl-3-azido-a,b-L-lyxo- 131 Actinorhodin, diepoxy 295 hexopyranosyl acetate AFN-1252 571 4-O-Benzyl-2,3,6-trideoxy-3-C-methyl-3- 131 Albaflavenone 387 trifluoroacetamido-a,b-L-lyxo-hexopyranosyl acetate Albocycline 303 (S, Z)-3-Benzylidene-6-isopropylpiperazine-2,5-dione 31 Allosamizoline 123 (S, Z)-3-Benzylidene-6-methylpiperazine-2,5-dione 31 N-Allyl-aclacinomycin A 165 3-Benzylpiperazine-6-(4-methoxybenzylidene)-2,5-dione 31 (4R*,6R*,8S*)-8-Allyl-9,9-dimethyl-1-methoxy-4- 141 Bhimamycin F, H, I 719 prenyl-6-((triisopropylsilyloxy)methyl)bicyclo Biapenem 571 [3.3.1]non-1-ene-3,5-dione Biemodin 491 (4S*,6R*,8S*)-3-(8-Allyl-9,9-dimethyl-1-methoxy-6- 141 Brartemicin analogs 531 ((triisopropylsilyloxy)methyl)bicyclo[3.3.1]non-1- Brilacidin 571 ene-3,5-dione-4-yl)methyl)-2,2-dimethyloxirane (3S)-4-Bromo-2,3-dimethylbut-1-ene 147 (4S*,6R*,8S*,18S*)-8-Allyl-18-(1-hydroxy-1-methylethyl) 141 (2E,5R)-1-tert-Butyldiphenylsilyloxy-5- 155 -9,9-dimethyl-6-((triisopropylsilyloxy)methyl)-31- methanesulfonyloxy-2-methylhex-2-ene
    [Show full text]