He discarded the contaminated plates into a Lysol basin. When he returned, he found several cultures contaminated with molds. Before leaving for vacation, he inoculated culture plates with Staphylococcus colonies and stacked the plates on the corner of his laboratory bench. In the summer and early fall of 1928, Fleming was studying the relationship between colony morphology of Staphylococcus and their virulence ( 14). In addition, he used the mycolysate on human subjects in 1930 and obtained considerable success ( 13).įrom these accounts, Fleming was therefore not the first to observe antibiosis between the fungal and bacteria in a vessel, but without controversy, he was the first to study the substance he termed “penicillin”.Īntibiotic hall of fame. The mycolysate was non-toxic when introduced into guinea pigs and rabbits. Gratia called the lytic agent “mycolysate”. This airborne contaminant was next demonstrated to attack killed cultures of Pseudomonas aeruginosa, Mycobacterium tuberculosis and Escherichia coli. A culture of white actinomycete grew on the plate surrounded by a clear zone of dissolved bacteria. In classic experiments performed in 1925–1926, Gratia and his assistants exposed a 2 % water agar plate containing dead Staphylococcus to the laboratory air.
He then found that co-injection of a normally lethal dose of Salmonella typhi, the causative agent of typhoid fever, with Penicillium glaucum prevented the animals from contracting typhoid ( 12).Īnother notable pioneer was Gratia, a Belgian scientist who did ground-breaking research on the phenomenon of bacteriolysis and its application to the defeat of bacteria pathogens ( 13). While completing his doctoral degree in 1897, Ernest Duschesne found antagonism between Penicilium and Escherichia coli in vitro. By the end of the 19th century, not only was this phenomenon well accepted, but it was also given a name – antibiosis ( 11).Ī few researches showing the contradictory effects between Penicillium and bacteria predate the now famous studies of Alexander Fleming and received little attention until after the clinical importance of penicillin was established. Initial work by Corneil and Babes and substantiated by experiments by Garre, firmly established that microbial antagonism was caused by the action of a diffusible substance produced by one organism on another ( 9, 10). For example, in a later work, Tyndall surmised that the bacterial growth inhibition observed in the presence of Penicillium was due to limiting oxygen conditions ( 8). Further evidence that Lister understood the clinical relevance of the antagonism is his reported treatment of infected wounds with Penicillium in 1884 ( 6).Īlthough many observed microbial antagonism, the concept that the phenomenon was caused by the production of a compound by one microorganism that could kill another was not immediately apparent. One of the earliest references to the therapeutic potential of the inhibition of bacterial growth by other microorganisms was in Pasteur and Joubert’s descripton of the inhibition of anthrax by air-borne organisms ( 7). Although perhaps only Roberts and Lister realized that their findings could be due to the action of an antibacterial compound, these observations are noteworthy nonetheless ( 6).
Others, including William Roberts, John Tyndall and Joseph Lister reported similar observations with Penicillium ( 3– 5).
The possibility of one organism interfering with the growth of another has been the subject of intense investigation since the early days of microbiology, In 1871, Sir John Burdon-Sanderson observed that media exposed to air rapidly became turbid with bacteria, but if a Penicillium mold happened to grow on the surface of the broth, less turbidity ensued ( 2). These early examples of remedies include applying molds to opened cuts and wounds, and eating radishes, leeks, garlic and onions that are now known to be anti-bacterial. The concept of using of chemicals to alleviate diseases, particularly infectious diseases, dates back to the Ancient Egypt, Babylon, the Far East and the Incas ( 1).
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