Kathrin I. Mohr

The discovery of new antibiotics is mandatory with regard to the increasing number of resistant pathogens. One approach is the search for new antibiotic producers in nature. Among actinomycetes, Bacillus species, and fungi, myxobacteria have been a rich source for bioactive secondary metabolites for decades. To date, about 600 substances could be described, many of them with antibacterial, antifungal, or cytostatic activity. But, recent cultivation-independent studies on marine, terrestrial, or uncommon habitats unequivocally demonstrate that the number of uncultured myxobacteria is much higher than would be expected from the number of cultivated strains. Although several highly promising myxobacterial taxa have been identified recently, this so-called Great Plate Count Anomaly must be overcome to get broader access to new secondary metabolite producers. In the last years it turned out that especially new species, genera, and families of myxobacteria are promising sources for new bioactive metabolites. Therefore, the cultivation of the hitherto uncultivable ones is our biggest challenge.

Two new secondary metabolites, labindole A [2-methyl-3-(2-nitroethyl)-3H-indole] (1) and labindole B [2-methyl-3-(2-nitrovinyl)-3H-indole] (2), were isolated from the myxobacterium Labilithrix luteola (DSM 27648^T). Additionally, four metabolites 3, 4, 5 and 6 already known from other sources were obtained. Their structures were elucidated from high resolution electrospray ionisation mass spectrometry (HRESIMS) and 1D and 2D nuclear magnetic resonance (NMR) spectroscopy data and their relative configuration was assigned based on nuclear Overhauser effect (NOE) and vicinal ¹H-NMR coupling data. The compounds where tested for biological activities; labindoles A (1) and B (2) exhibited significant activity against Hepatitis C Virus, 9H-carbazole (3), 3-chloro-9H-carbazole (4) and 4-hydroxymethyl-quinoline (5) showed antifungal activities. Moreover, compound 3 had weak to moderate antibacterial activities, while labindoles A (1) and B (2) were devoid of significant antifungal and antibacterial effects.

For thousands of years people were delivered helplessly to various kinds of infections, which often reached epidemic proportions and have cost the lives of millions of people. This is precisely the age since mankind has been thinking of infectious diseases and the question of their causes. However, due to a lack of knowledge, the search for strategies to fight, heal, and prevent the spread of communicable diseases was unsuccessful for a long time. It was not until the discovery of the healing effects of (antibiotic producing) molds, the first microscopic observations of microorganisms in the seventeenth century, the refutation of the abiogenesis theory, and the dissolution of the question “What is the nature of infectious diseases?” that the first milestones within the history of antibiotics research were set. Then new discoveries accelerated rapidly: Bacteria could be isolated and cultured and were identified as possible agents of diseases as well as producers of bioactive metabolites. At the same time the first synthetic antibiotics were developed and shortly thereafter, thousands of synthetic substances as well as millions of soil borne bacteria and fungi were screened for bioactivity within numerous microbial laboratories of pharmaceutical companies. New antibiotic classes with different targets were discovered as on assembly line production. With the beginning of the twentieth century, many of the diseases which reached epidemic proportions at the time—e.g., cholera, syphilis, plague, tuberculosis, or typhoid fever, just to name a few, could be combatted with new discovered antibiotics. It should be considered that hundred years ago the market launch of new antibiotics was significantly faster and less complicated than today (where it takes 10–12 years in average between the discovery of a new antibiotic until the launch). After the first euphoria it was quickly realized that bacteria are able to develop, acquire, and spread numerous resistance mechanisms. Whenever a new antibiotic reached the market it did not take long until scientists observed the first resistant germs. Since the marketing of the first antibiotic there is a neck-on-neck race between scientists who discover natural or develop semisynthetic and synthetic bioactive molecules and bacteria, which have developed resistance mechanisms. The emphasis of this chapter is to give an overview of the history of antibiotics research. The situation within the pre-antibiotic era as well as in the early antibiotic era will be described until the Golden Age of Antibiotics will conclude this time travel. The most important antibiotic classes, information about their discovery, activity spectrum, mode of action, resistance mechanisms, and current application will be presented.