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Taxonomy
Taxonomy of Streptomyces
Fungi-like bacteria
Streptomyces spp. are Gram-positive aerobic bacteria of the order Actinomycetales within the class of Actinomycetes. The genus can be ubiquitously found in the soil. Although Streptomyces are eubacteria, they do not present in the usual bacterial coccoid or bacillary forms. In the contrary, they present as a network of filaments from which emerge aerial branches bearing chains of spores; a unique morphology that resembles filamentous fungi. Streptomyces bacteria are well adapted to the soil environment where they thrive as a substrate mycelium made of multiple hyphae that grow through tip extension and branch through the soil sourcing for nutrients.
This complex multicellular morphology had led earlier microbiologists to believe that the actinomycetes were fungi or intermediate links between fungi and bacteria. However, it is now proved beyond doubt that Streptomyces are indeed prokaryotes. Their genetic material, cell wall structure, and phages are similar to those of bacteria.
Phylogenetically, Streptomyces are a part of Actinobacteria. They possess genetic material (DNA) which are relatively rich in GC content (69-78%), when compared with other bacteria such as Escherichia coli (50%).
Prolific metabolite producer
Streptomyces colonies on agar plate
An important source of antibiotics
An important source of antibiotics
The most interesting property of Streptomyces is its unique ability to produce bioactive secondary metabolites. The diversity of secondary metabolites made by Streptomyces species has led some scientists to argue they are not simply chemical weapons used to kill other soil organisms but are signaling molecules which, at low doses, can modulate the transcription and translation of genes in target organisms. Although the concentrations of secondary metabolites in the natural environment are rarely known, it seems likely that antibiotic compounds are usually present in subinhibitory concentrations. Whatever the natural function of these secondary metabolites, it appears that their diversity evolved through interactions among bacteria and other organisms, and contemporary research have barely begun to sample or understand this chemical diversity.
Three Nobel laurates emerged from their pivotal discovery related to Streptomyces
Dr. Selman A. Waksman,
Winner of the 1952 Nobel Prize
for Physiology or Medicine
Dr. Selman A. Waksman
Dr. Selman A. Waksman
The discovery of Streptomyces spp. natural products was pioneered by Selman Waksman, a soil microbiologist who, after two decades of studying the actinomycetes as members of the soil microbial community, was inspired by the exploitation of Alexander Fleming's discovery of the first natural product antibiotic, penicillin. The genus Streptomyces was proposed by Waksman & Henrici in 1943. They were classified in the family Streptomycetaceae.
Student Albert Schatz, acting under his direction, found the culture that produced the new antibiotic streptomycin, and it was quickly established as the prime treatment for tuberculosis worldwide, as well as for many diseases caused by Gram-negative bacteria that were not previously treatable. These events provided the basis for Dr. Waksman receiving the Nobel Prize in 1952.
The discovery of antibiotics produced by streptomycetes in the 1940s led to extensive screening for novel bioactive compounds and subsequently the need for patenting led to an over classification of the genus. Producers of novel natural products were described as new species and patented. Species described within the genus Streptomyces increased from approximately 40 to over 3000. Many of these strains were considered to be synonyms. Standard identification criteria and type strains were needed to prevent over speciation. In 1964, the International Streptomyces Project (ISP) was initiated to introduce standard criteria for the determination of species so as to reduce the number of poorly described synonymous species.
Professor Selman Waksman with graduate student Albert Schatz.
Laboratory photograph during the studies leading to the discovery of streptomycin, 1944.
Dr. Satoshi Ōmura
Dr. Satoshi Ōmura
Satoshi Ōmura is a Japanese microbiologist and expert in isolating natural products. He developed unique methods for large-scale culturing and characterization of Streptomyces. Equipped with extraordinary skills working with these bacteria, Ōmura isolated new strains of Streptomyces from soil samples and successfully cultured them in the laboratory. From many thousand different cultures, he selected about 50 of the most promising, with the intent that they would be further analyzed for their activity against harmful microorganisms. One of these cultures later turned out to be Streptomyces avermitilis, the source of Avermectin.
Dr. William C. Campbell
Dr. William C. Campbell
William C. Campbell is an expert in parasite biology in the USA. He acquired Ōmura’s Streptomyces cultures and explored their efficacy. Campbell showed that a component from one of the cultures was remarkably efficient against parasites in domestic and farm animals. The bioactive agent was purified and named Avermectin, which was subsequently chemically modified to a more effective compound called Ivermectin. Ivermectin turned out to be highly effective in both animals and humans against a variety of parasites, including those that cause River Blindness and Lymphatic Filariasis.
Collectively, Ōmura and Campbell’s contributions led to the discovery of a new class of drugs with extraordinary efficacy against parasitic diseases. The discovery of this novel drug class have have revolutionized therapy for patients suffering from devastating parasitic diseases. Today, the Avermectin-derivative Ivermectin is used in all parts of the world that are plagued by parasitic diseases. The treatment is so successful that these diseases are on the verge of eradication, which would be a major feat in the medical history of humankind.
Future outlook
Limitless potentials
Limitless potentials
The fact that three nobel laureates emerged from the studies directly related to Streptomyces depicts the limitless potentialities yet to be exploited from the genus.
Today, streptomycetes are the primary producers of more than half of the 10,000 documented bioactive compounds and have offered over 50 years of interest to industry and academia. Streptomycetes are recognized as the most important source of antibiotics for medical, veterinary and agricultural use. Besides being renowned as the prolific producer of a plethora of agents with species-specific antibacterial properties, they have also been exploited as antifungals, antivirals, antitumoral, anti-hypertensives, and even as immunosuppressants.
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