Antibiotics – serie

The idea for publishing these books on the mechanism of action and on the biosynthesis of antibiotics was born of frustration in our attempts to keep abreast of the literature. Gone were the years when we were able to keep a biblio­ graphy on antibiotics and feel confident that we could find everything that was being published on this subject. These fields of investigation were moving for­ ward so rapidly and were encompassing so wide a range of specialized areas in microbiology and chemistry that it was almost impossible to keep abreast of developments. In our naivete and enthusiasm, however, we were unaware that we were toying with an idea that might enmesh us, that we were creating an entity with a life of its own, that we were letting loose a Golom who instead of being our servant would be our master. That we set up ideals for these books is obvious; they would be current guides to developments and information in the areas of mechanism of action and bio­ synthesis of antibiotics. For almost every subject, we wished to enlist the aid of an investigator who himself had played a part in determining the nature of the phenomena that were being discussed. One concept for the books was that they include only antibiotics for which a definitive, well-documented mechanism of action or biosynthetic pathway was known.

The idea for publishing these books on the mechanism of action and on the biosynthesis of antibiotics was born of frustration in our attempts to keep abreast of the literature. Gone were the years when we were able to keep a biblio­ graphy on antibiotics and feel confident that we could find everything that was being published on this subject. These fields of investigation were moving for­ ward so rapidly and were encompassing so wide a range of specialized areas in microbiology and chemistry that it was almost impossible to keep abreast of developments. In our naivete and enthusiasm, however, we were unaware that we were toying with an idea that might enmesh us, that we were creating an entity with a life of its own, that we were letting loose a Golom who instead of being our servant would be our master. That we set up ideals for these books is obvious; they would be current guides to developments and information in the areas of mechanism of action and bio­ synthesis of antibiotics. For almost every subject, we wished to enlist the aid of an investigator who himself had played a part in determining the nature of the phenomena that were being discussed. One concept for the books was that they include only antibiotics for which a definitive, well-documented mechanism of action or biosynthetic pathway was known.

This volume is the third in the series devoted to Antibiotics initiated by Springer Verlag in 1967. The first two volumes were devoted to the Mode of Action of Antibiotics and Biogenesis, respectively and were received graciously. During the intervening years these two works have been used often by research workers and students alike and have been quoted extensively. Although a number of other excellent treatises on antibiotics have appeared, the Springer series has set a standard for thoroughness and quality that meets the need of the scientific community. It is against this background that the present Editors set about the preparation of a third volume in the Series on Antibiotics. Since the appearance of Volume I, also dealing with Mechanism of Action, tremendous strides have been made in the depth and breadth of our knowledge of molecular biology, microbial chemistry and molecular pharmacology and of their direct application to studies on the mode of action of drugs. The field of molecular biology itself was in its relative infancy during the preceding decade and the unique role played by many anti­ biotics in the development of our understanding of nucleic acid synthesis and function and its relationship to protein synthesis and cell physiology has led rapidly to a very precise, understanding of how many of these same antibiotics inhibit susceptible cells.

The first volume of Antibiotics was published in 1967 and contained a series of review papers on antibiotic actions. The editors, Drs. GOTTLIEB and SHAW, were aware of the rapid development of this field of study and provided a number of addenda in an effort to keep knowledge up to date while the book was in production. One year after the publication of Antibiotics I, this editor had a conference with Dr. KONRAD F. SPRINGER in which it became clear that another volume on actions of antibiotics would be necessary. For a variety of reasons, this was delayed until 1975 and became Antibiotics III. It did not contain addenda since it was recognized by the editors, Drs. CORCORAN and HAHN, that still another volume would have to follow and that in a moving field, such as the study of the actions of antibacterial drugs, no publication can be definitive or remain current, except for a limited period of time. The editors of Volume III grouped the contributions into sections: 1. Inter­ ference with nucleic acid biosyntheses, 2. Interference with protein biosynthesis, and 3. Interference with cell wall/membrane biosynthesis, specific enzyme sys­ tems, and those in which the mode of action was not known with certainty.

When Antibiotics I was published in 1967, the teleological view was held by some that" antibiotics" were substances elaborated by certain microorgan­ isms for the purpose of competing with other microorganisms for survival in mixed ecological environments. However, not only had J. EHRLICH and his associates shown 15 years earlier that chloramphenicol was produced by Strepto­ myces venezuelae in cultures of sterilized soils but not in parallel cultures of the same soils which were not sterilized, but operationally, the search for anti­ cancer antibiotics was actively under way (Antibiotics I reporting on numerous such substances), although the concept of antibiosis could not logically justify such undertakings. This editor hesitates to accept the use of the term "antibiotic" for anti­ microbial agents of non microbiological origins which is sometimes encountered, but neither does he subscribe to the view that antibiotics are in some fundamental manner different from chemotherapeutic substances of other origins. Modes and mechanisms of action of chemotherapeutic compounds are not systematic functions of their origins nor of the taxonomical position of the target organisms. Consequently, in the selection of topics for Antibiotics III (published in 1975), synthetic drugs and natural products of higher plants (alkaloids) were represented, along with antibiotics in the strict sense of the definition. We now present Antibiotics V, for whose assembly the same selection criteria were applied as for Antibiotics Ill. The aggregate length of the contributions rendered it impractical to place the entire text between the covers of one book.

The Series on Antibiotics produced by Springer-Verlag began more than a decade ago with the nearly simultaneous appearance of two volumes, one dealing with the mode of action of antibiotics and the other concerning the biosynthesis of them. The standards set by the original Editors were high, and these books have proved useful to many. The rapid advances in our knowl­ edge of the mode of action of antibiotics and other antitumor agents has stimu­ lated two further works in the same series (Volume III, 1975; and Volumes Vj1 and Vj2, 1979). For some time it had appeared to Dr. Konrad Springer that the time might' be ripe' for bringing the subject of the biosynthesis of antibiotics up-to-date. This Editor agreed to survey the literature and discuss this possibility with his colleagues who are active in research on antibiotics. In spite of the appearance of numerous review articles, both of a highly special­ ized and general nature, on the biosynthesis of antibiotics, it was agreed generally that it would be extremely useful to add a new volume on biosynthesis to the Series. Such a work should focus on collecting a group of contributions dealing with those antibiotics whose biosynthesis is understood in much greater detail now than it was in the middle 1960's. Since Volume II on biosynthesis continues to be available, this addition to the series has not dealt with each and every antibiotic whose biosynthesis was studied long ago.

It is not certain that the editors of Antibiotics I (1967), Drs. GOTTLffiB and SHAW, fully realized that they were laying the foundation for an entire series of which we present here Vol. VI. For some time to come, this will be the last volume of the Antibiotics series. There are several reasons for this. Firstly, the discovery of medicinally useful antibiotics has leveled off, because the number of microbiological products with antimicrobial properties is not infinite. In 1972 some 2500 antibiotic substances were known, of which approximately one per cent are clinically useful. Further search for antibiotics has led to increasing frequency of rediscoveries and drasti­ cally decreasing frequency of discoveries of new antibiotics. As the search for antibiotics with a standard methodology in conventional ecological niches has exhausted itself, there is a paucity of new and interesting substances on which to undertake modes/mechanisms of action studies. Secondly, the mechanism of action field has come of age and its results are now academic knowledge. This also holds true for synthetic chemothera­ peutic drugs and becomes the case rapidly for toxic substances with anti-eukar­ yotic action. The study of mechanisms of action was undertaken for two reasons: one was the basic scientific desire to know how antimicrobial substances inter­ fered with microbial biochemistry; the second one was the hope that such infor­ mation would be useful in the premeditated design of synthetic antimicrobials.