Abstract
Growth of Streptomyces in submerged culture is characterized by the formation of complex mycelial particles, known as pellets or clumps, which strongly influence antibiotic production. Also, many bioactive molecules produced by Streptomyces have great potential to modulate soil bacteria morphological development. However, there has been no effort directed at engineering mycelial morphology using these small molecules. Here, thiostrepton was identified, using a combination of qRT-PCR, semi-preparative HPLC, and MALDI-TOF MS, as a pellet-inducing compound produced by S. laurentii ATCC31255. At sub-inhibitory concentration, thiostrepton stimulated Streptomyces coelicolor M145 pellet formation and antibiotics production were altered, with 3-fold and 2-fold decreases in actinorhodin and undecylprodigiosin yields, respectively. It was also shown that mycelial morphology can be influenced by other antibiotic class at sub-inhibitory concentrations. For instance, in the presence of spectinomycin, S. coelicolor M145, which under typical growth conditions forms large diameter pellets with many protruding hyphae, instead formed small diameter pellets with barely visible hyphae at the edge. Importantly, this morphology produced a 4-fold increase in undecylprodigiosin production and 3-fold decrease in actinorhodin production. These results indicated that these small molecules, previously identified as antimicrobials, also have great potential for influencing mycelial morphology.
Highlights
Actinobacteria and, in particular Streptomyces species, show filamentous growth from single spores and are able to produce thousands of chemically complex, natural, bioactive metabolites
There exists a strong link between mycelial morphology and antibiotics production in streptomycetes, but the relationship between mycelial morphology and antibiotics production in S. coelicolor M145 was not clear
We investigated whether a different mycelial morphology favouring antibiotics production could be generated by overexpression of cslA
Summary
Actinobacteria and, in particular Streptomyces species, show filamentous growth from single spores and are able to produce thousands of chemically complex, natural, bioactive metabolites. There is a critical pellet size for erythromycin production[7] It is of particular importance, through the application of genetic approaches, to engineer the mycelial morphology of industrial strains. The polyether antibiotic promomycin, as well as nigercin and monensin, have been shown to stimulate antibiotic production in Streptomyces spp.[18] These observations raise the possibility that diverse, bioactive, small molecules secreted by Streptomyces might have some positive or negative influences on mycelial morphology. In the presence of chloramphenicol, erythromycin, and tetracycline, no differences were observed in mycelial morphology and antibiotic production, compared to the control group When these bacteria were treated with spectinomycin, the formation of pellets with smaller diameter and barely visible hyphae at the surface were observed. For the first time, regulation of mycelial morphology is reported through the addition of antibiotics
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