The 4-Quinolones: Anti Bacterial Agents in Vitro PDF
Preview The 4-Quinolones: Anti Bacterial Agents in Vitro
Springer Series in Applied Biology The 4-Quinolones: Anti Bacterial Agents in Vitro Springer Series in Applied Biology Series Editor: Prof. Anthony W. Robards PhD, DSc, FIBiol Proposedfuture titles: Food Freezing in the 1990's and Beyond Ed. W. B. Bald Biodegradation of Natural and Synthetic Materials Ed. W. B. Betts Critical Loads of Environmental Pollutants Ed. M. J. Chadwick Separation and Immobilisation of Biomolecules Ed. U. B. Sleytr Gene Transfer in Eukaryotic Cells Ed. J. R. Ware The 4-Quinolones: Anti Bacterial Agents in Vitro Edited by G. C. Crumplin Springer-Verlag London Berlin Heidelberg New York Paris Tokyo Hong Kong Geoff Crumplin Department of Biology, University of York, YorkYOI 5DD Series Editor Professor Anthony William Robards, BSc, PhD, DSc, DipRMS, FIBiol Director, Institute for Applied Biology, University of York, York YOI 5DD, UK Cover Illustration: Electron micrograph of uropathogenic Escherichia coli showing Type 1 pili ISBN-13: 978-1-4471-3451-0 e-ISBN-13: 978-1-4471-3449-7 DOl: 10.1007/978-1-4471-3449-7 British Library Cataloguing in Publication Data The 4-Quinolones: antibacterial agents in vitro, 1. Medicine. Drug therapy. Quino1ones I. Crumplin, Geoffrey 1946- 615'.3 Library of Congress Cataloging-in-Publication Data The 4-quinolone: antibacterial agents in vitro/edited by G. C. Crumplin p.cm.-(Springer series in applied biology) Includes bibliographical references. 1. Quinolone antibacterial agents - Physiological effect. 2. Microbial sensitivity tests. 3. DNA topoisomerase ll. I. Crumplin, G. C. (Geoff C.), 1946- . ll. Series. RM666.Q55AI41990 89-26200 61S.7 -dc20 ClP Apart from any fair dealing for the purposes of research or private study, or criticism or review, as permitted under the Copyright, Designs and Patents Act 1988, this publication may only be reproduced, stored or transmitted, in any form or by any means, with the prior permission in writing of the publishers, or in the case of reprographic reproduction in accordance with the terms of licences issued by the Copyright Licensing Agency. Enquiries concerning reproduction outside those terms should be sent to the publishers. Ie Springer-Verlag London Limited 1990 Softcover reprint of the hardcover 18t edition 1990 The use of registered names, trademarks etc .. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant laws and regulations and therefore free for general use. Set by Institute for Applied Biology, University of York Foreword from Series Editor Biology, and its applications for the benefit of mankind., represents one of the most crucial and rapidly moving areas of scientific study as we enter the last decade of the 20th century. The Institute for Applied Biology represents one of Britain's largest and best integrated teams of research biologists to be found within a single academic department, while Springer-Verlag is one of the world's outstanding publishing houses in the area of science and medicine. The combination of these two forces leads to the publication of the "Springer Series in Applied Biology" which will become a major reference work in its own subject area. As is to be expected from a large and multidisciplinary Department, the range of seminars will extend from the study of foams to ecotoxicology and from biodegradation to genetic engineering. The aim will be to keep abreast of topics that have a special, applied, and contemporary interest. Up to four volumes will be published each year through the editorial office in York. Modern methods of manuscript assembly will streamline the publication process without losing quality and, crucially, will allow the books to be available in the shops within four to five months of the actual seminar. In this way authors will be able to publish their most recent work without fear that it will, as so often happens, become outdated during an overlong period between submission and publication. Our aim is to maintain the highest standards of both science and publication quality while minimising the delay between submission and publication. While the choice of subjects for seminars is made by our own editorial board, we are also always pleased to receive suggestions from external sources or, indeed, to consider the organisation and publication of seminars on topics other than those of direct interest to the Institute for Applied Biology. The applications of biology are fundamental to the continuing welfare of all people, whether by protecting their environment or by ensuring the health of their bodies. This series aims to become an important means of disseminating the most up-to-date information in this field. York, November 1989 A. W. Robards Editor's Preface The 4-quinolone antibacterial agents arose by Serendipity, and to a large extent have evolved in the same manner to the highly potent antibacterial agents which are now being advocated as potential 'drugs of frrst choice' for the treatment of a wide range of bacterial infections. It is now clearly established that they kill susceptible bacterial cells as a consequence of a unique mechanism of action upon what is a unique target molecule within the cell. However, fundamental biological studies of the effects of the 4-quinolones upon susceptible cells (even those carried out before the target molecule had been identified) have shown that the sheer diversity of effects upon cellular metabolism, control, and behaviour is limited only by the number of biological processes in the cell which involve DNA. Such a diversity of effects is not associated with any other group of antibacterial agents. The in vitro evaluation of 4-quinolones represents an important component of the development programme leading up to possible clinical use, as well as a means of monitoring and developing clinical usefulness. The scientific meeting on which this book is based was convened in order to provide a forum for the bringing together of many of the in vitro study procedures so that an overall philosophical question might be addressed. This philosophical question arises out of the accepted belief that the 4-quinolones are an unusual (if not unique) group of antibacterial agents and may be phrased as -"Are the 4-quinolones just like other antibacterials?" The evaluation and clinical use of antibacterial agents in the 1980s is carried out in the context of the principles of chemotherapy which were defined as long ago as 1912 by Paul Ehrlich. Up until the advent of the 4-quinolones, antibacterial agents have apparently conformed to these principles by functioning as fairly straightforward selective toxins, and techniques of experimentation and interpretation have become standardized. An antibacterial agent (such as a b-lactam, a sulphonamide, macrolide, aminoglycoside or tetracycline) is described as an agent which either inhibits the growth of susceptible bacterial cells or which renders the bacteria non viable. In contrast 4-quinolone agents have been variously described viii Editor's Preface as;-bactericidal agents, mutagens, anti-mutagents, modifiers of gene expression control, promoters or inhibitors of genetic transposition, DNA-damaging agents, plasmid-curing agents, recombinogens, anti recombinogens, inhibitors of DNA-synthesis, inhibitors of RNA synthesis etc... Some of these descriptions conform to the basic definition of an antibacterial agent, but some clearly do not It is of course convenient to maintain continuity of perception and methodology, but once in a while we have to ensure that what we are doing is justified. It is just possible that the 4-quinolone antibacterial agents represent not only a good opportunity to try and justify uniformity, but also that they may represent an instance where uniformity of treatment might not be fully justified. This Advanced Study Seminar was convened as a forum to relate what we do and do not know about the 4-quinolones in vitro, and to discuss how this knowledge might allow us to ensure that data derived from in vitro studies might relate to the clinical application of the 4-quinolones. Geoff Crumplin Contents 1 Quinolones as Broad-Spectrum Agents H. C. Neu.............................................................................. 1 2 Effects of Physiological Cation Concentration on 4-Quinolone Absorption and Potency J. T. Smith... ............ ............ ......................... ............. ............ 15 3 The Innuence of Oxygen upon Bactericidal Potency I. Morrissey, C. S. Lewin and J. T. Smith.................................... 23 4 Interactions of 4-Quinolones with Other Agents - the Importance in Assessing Practical Antibacterial Potency C. S. Lewin and J. T. Smith....................................................... 37 5 Molecular Effects of 4-Quinolones upon DNA Gyrase G. C. Crumplin ....................................................................... 53 6 Mechanisms of Killing of Bacteria by 4-Quinolones J. S. Wolfson and D. C. Hooper.................................................. 69 7 Use of an in vitro DNA Strand-Breakage Assay to Monitor Compound Interactions with DNA Gyrase L. P. Elwell, L. M. Walton, J. M. Besterman and A. T. Hudson....... 87 8 Comparisons of DNA Gyrases from Different Species N. J. R. Robillard, B. L. M. Masecar, B. R. Brescia and R. A. Celesk............... .................. .................................. ......... 103 9 Structure-activity Relationships of Fluoro-4-Quinolones L. A. Mitscher, P. V. Devasthale and R. M. Zavod......................... 115 x Contents 10 Aspects of Quinolone--DNA Interactions L. L. Shen. J. Baranowski. M. Nuss. J. Tadanier. C. Lee. D. T. W. Chu and J. J. Plattner .................................................. 147 11 Selective Toxicity: the Activities of 4-Quinolones against Eukaryotic DNA Topoisomerases T. D. Gootz. J. F. Barrett. H. E. Holden. V. A. Ray and P. R. McGuirk......................................................................... 159 12 In vitro Genotoxity Assessment and the Effects of 4-Quinolones upon Human Cells G. C. Crumplin........................................................................ 173 13 Mechanisms of Bacterial Resistance to 4-Quinolones D. C. Hooper........................................................................... 201 14 In vitro and in vivo Mutation Frequencies to Resistance - do they Correlate in the Long Term? J. T. Smith. .... ........ ....... ..... ............... ........... .... ..... ........ .... ...... 215 15 Measurement of the Frequency of Mutation to Resistance - the Importance of Testing under Physiological Conditions M. Odell ................................................................................ 229 16 Plasmid-borne Resistance to 4-Quinolones -- a Real or an Apparent Absence? P. Courvalin. C. Poyart-Salmeron and E. Derlot............................. 241 Poster Presentations Anaerobiosis and staphylococcal resistance to certain 4-quinolones D. J. C Knowles. G. T. Grimes and L. S. Holmes.......................... 249 Gram Negative Mutants Resistant to 4-Quinolones: Are they Competent Pathogens? G. C. Crumplin................ .................. ....... ....... ........ ........ ........ 257 Quinolone-Resistant E. Coli Mutants Overproduce a 60 kDa Protein Highly Homologous to GroEL P. Hallett. A. Mehlert and A. Maxwell......................................... 269 Subject Index Contributors Mr. J. Baranowski Department 47N, Building AP9A Abbott Laboratories, Abbott Park, Illinois 60064, USA Dr. J. F. Barrett The R. W. Johnson Pharmaceutical Research Institute, Raritan, NJ 08869 0602, USA Dr. J. M. Besterman Department of Molecular Biology, Burroughs Wellcome Company, 3030 Cornwallis Road, Research Triangle Park, NC 27709, USA Ms. B. R. Brescia Miles Inc, Pharmaceutical Division, 400 Morgan Lane, West Haven, CT 06516, USA Dr. R. A. Celesk Miles Inc, Pharmaceutical Division, 400 Morgan Lane, West Haven, CT 06516, USA Dr. D. T. W. Chu Department 47N, Building AP9A Abbott Laboratories, Abbott Park, Illinois 60064, USA Dr. P. Courvalin Institut Pasteur, 28 Rue du Dr Roux, 75724 Paris, Cedex 15, France Dr. G. Crumplin Department of Biology, University of York, York Y01 SOD Dr. E. Derlot Institut Pasteur, 28 Rue du Dr Roux, 75724 Paris, Cedex 15, France Mr. P. V. Devasthale Department of Medicinal Chemistry, Kansas University, Lawrence, KS 66045, USA
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