Gian Gualberto Gallo

The Mechanism of Action of Antibiotics

The information and the concepts discussed in this chapter have been organized using three approaches: (1) systematic, (2) experimental, and (3) with examples.

Antibiotics and Producer Organisms

What is the “natural” function of antibiotics, or, in other terms, what “evolutionary advantage” is conferred on a microbial strain by its ability to produce an antibiotic substance? Why is the ability to produce antibiotics more common in certain taxonomic groups than in others? During 30 years of intense antibiotic research several hypotheses have been put forth in answer to the above questions. In evaluating such hypotheses it is important to remember that antibiotics are a heterogeneous class of compounds in structure, biosynthetic origin, and mechanism of action and that they are the products of vastly differing organisms. Therefore, there may be more than one function of antibiotic substances, and they may confer different evolutionary advantages on different producing organisms.

The Use of Antibiotics

The term chemotherapy refers to treatment of diseases of microbial origin by the systemic administration of antibiotics or other drugs. Basically, this involves inhibition of the multiplication of the infectious microorganism through selective toxicity, without interfering with the function of the host, thereby enabling the host’s defense mechanisms to overcome the infection. It is beyond the scope of this book to undertake a detailed analysis of the methods or of the uses of chemotherapy, i.e., why a particular antibiotic is used for a given infection and how it is administered. However, it is important to analyze the basic principles of chemotherapy, which can be stated briefly as follows:

Biosynthesis and Genetics of Antibiotic Production

The study of biochemical and genetic aspects of antibiotic production is of great interest because it casts light on the mechanisms of cellular differentiation. It is also important for two practical reasons: the improvement of production yields and the possibility of directing the fermentation process toward products with desired characteristics.

The Search for and Development of New Antibiotics

The search for new antibiotics, fifty years after the introduction of penicillin into clinical use, continues to be very active. In fact, there are still microorganisms against which the available drugs are not effective, and the spread of resistant strains has made some antibiotics that once were very effective practically useless. On the other hand, new antibiotics are still being found despite many decades of intensive search.

The Activity of Antibiotics

The activity of an antibiotic reflects its ability to inhibit microbial growth. While the concept of antibiotic activity appears simple and straightforward, the quantitative expression of antibiotic activity is complex and depends on the assay method and the conditions under which the test microorganism is grown.

Activity of Antibiotics in Relation to Their Structure

Since it was observed that different natural penicillins display different biological properties, the study of the relationship between chemical structure and microbiological activity in an antibiotic molecule has become of major interest.