Chapter 1 : Antibiotics: Initial Concepts

Abstract:

Antibiotics are molecules that stop microbes, both bacteria and fungi, from growing or kill them outright. Evaluation of new antibacterial molecules typically follows a hierarchical procedure. A new compound is tested against a panel of bacterial strains, many of them pathogens arising from clinical isolates, and many of those possessing resistance to prior generations of antibiotics. If a new antibiotic candidate shows sufficient potency against marker strains, then the molecule may be evaluated in animals inoculated to have high levels of infections with specific strains of bacteria in particular tissues to see if the candidate molecule is protective and/or curative. The new antibiotic may then be compared against standard antibiotics used against such bacterial infections, with both antibiotic-sensitive and antibiotic-resistant strains of pathogens. Bacteria and fungi that make antibiotics need self-protection or autoimmunity mechanisms to protect themselves from the lethal chemical weapons they are producing. Two contemporary approaches for identifying new molecules active against resistant pathogenic bacteria are the continued screening of microbial broths for new antibiotics and the development of large synthetic libraries from combinatorial chemical approaches. In the hundreds of millions of years that antibiotics have been produced by some subsets of bacteria and fungi to act on their neighbors, evolutionary pressure has been at work for the bacteria under attack to devise resistance mechanisms to survive. In the 70 years of the antibiotic era in the treatment of human infectious disease, pathogenic bacteria have developed relentlessly with clinically significant resistances to one class of antibiotic after another.