Spore awakening is a series of actions that starts with purely physical processes and continues via the launching of gene expression and metabolic activities, eventually achieving a vegetative phase of growth. In spore-forming microorganisms, the germination process is controlled by intra- and inter-species communication. However, in the Streptomyces clade, which is capable of developing a plethora of valuable compounds, the chemical signals produced during germination have not been systematically studied before. Our previously published data revealed that several secondary metabolite biosynthetic genes are expressed during germination. Therefore, we focus here on the secondary metabolite production during this developmental stage. Using high-performance liquid chromatography-mass spectrometry, we found that the sesquiterpenoid antibiotic albaflavenone, the polyketide germicidin A, and chalcone are produced during germination of the model streptomycete, S. coelicolor. Interestingly, the last two compounds revealed an inhibitory effect on the germination process. The secondary metabolites originating from the early stage of microbial growth may coordinate the development of the producer (quorum sensing) and/or play a role in competitive microflora repression (quorum quenching) in their nature environments.

The complex development undergone by Streptomyces encompasses transitions from vegetative mycelial forms to reproductive aerial hyphae that differentiate into chains of single-celled spores. Whereas their mycelial life – connected with spore formation and antibiotic production – is deeply investigated, spore germination as the counterpoint in their life cycle has received much less attention. Still, germination represents a system of transformation from metabolic zero point to a new living lap. There are several aspects of germination that may attract our attention: (1) Dormant spores are strikingly well-prepared for the future metabolic restart; they possess stable transcriptome, hydrolytic enzymes, chaperones, and other required macromolecules stabilized in a trehalose milieu; (2) Germination itself is a specific sequence of events leading to a complete morphological remodeling that include spore swelling, cell wall reconstruction, and eventually germ tube emergences; (3) Still not fully unveiled are the strategies that enable the process, including a single cell’s signal transduction and gene expression control, as well as intercellular communication and the probability of germination across the whole population. This review summarizes our current knowledge about the germination process in Streptomyces, while focusing on the aforementioned points.

Streptomycetes, typical soil dwellers, can be detected as common colonizers of human bodies, especially the skin, the respiratory tract, the guts and the genital tract using molecular techniques. However, their clinical manifestations and isolations are rare. Recently they were discussed as possible "coaches" of the human immune system in connection with certain immune disorders and cancer. This work aimed for the characterization and evaluation of genetic adaptations of a human-associated strain Streptomyces sp. TR1341. The strain was isolated from sputum of a senior male patient with a history of lung and kidney TB, recurrent respiratory infections and COPD. It manifested remarkably broad biological activities (antibacterial, antifungal, betahemolytic, etc.). We found that, by producing specific secondary metabolites, it is able to modulate host immune responses and the niche itself, which increase its chances for long-term survival in the human tissue. The work shows possible adaptations or predispositions of formerly soil microorganism to survive in human tissue successfully. The strain produces two structural groups of cytotoxic compounds: 28-carbon cytolytic polyenes of the filipin type and actinomycin X2. Additionally, we summarize and present data about streptomycete-related human infections known so far.

Regulatory RNAs control a number of physiological processes in bacterial cells. Here we report on a 6S-like RNA transcript (scr3559) that affects both development and antibiotic production in Streptomyces coelicolor. Its expression is enhanced during the transition to stationary phase. Strains that over-expressed the scr3559 gene region exhibited a shortened exponential growth phase in comparison with a control strain; accelerated aerial mycelium formation and spore maturation; alongside an elevated production of actinorhodin and undecylprodigiosin. These observations were supported by LC-MS analyses of other produced metabolites, including: germicidins, desferrioxamines, and coelimycin. A subsequent microarray differential analysis revealed increased expression of genes associated with the described morphological and physiological changes. Structural and functional similarities between the scr3559 transcript and 6S RNA, and its possible employment in regulating secondary metabolite production are discussed.

AH made the genetic manipulations with the streptomycete strain, performed fermentations and cocultures with human cells, prepared the metabolic extracts, and performed cytotoxicity and immunomodulatory effects assays of the extracts. EC performed the phylogenetic analyses, analyzed the genomic data and made the hemolysis and growth-inhibitory activities assays in vivo. AC supervised the phylogenetic analyses and analyzed the data, performed the genome sequencing, and participated in the manuscript preparation. HL, PP, and JH assayed the human cells-targeted activities. HL designed and performed the in vivo cocultures and evaluated their effects. PP, JH, and AH designed and performed the experiments to assess immunomodulatory features of metabolic extracts and their cytotoxicity. JH and HL evaluated the human cells-related experiments data and participated in the manuscript preparation. MČ performed and evaluated the LC-MS experiments. VK made the strain taxonomic and morphologic characterization. JB was involved in the growth-inhibitory activities in vivo and in evaluation of the strain interactions with

Streptomyces are of great interest in the pharmaceutical industry as they produce a plethora of secondary metabolites that act as antibacterial and antifungal agents. They may thrive on their own in the soil, or associate with other organisms, such as plants or invertebrates. Some soil-derived strains exhibit hemolytic properties when cultivated on blood agar, raising the question of whether hemolysis could be a virulence factor of the bacteria. In this work we examined hemolytic compound production in 23 β-hemolytic Streptomyces isolates; of these 12 were soil-derived, 10 were arthropod-associated, and 1 was plant-associated. An additional human-associated S. sp. TR1341 served as a control. Mass spectrometry analysis suggested synthesis of polyene molecules responsible for the hemolysis: candicidins, filipins, strevertene A, tetrafungin, and tetrin A, as well as four novel polyene compounds (denoted here as polyene A, B, C, and D) in individual liquid cultures or paired co-cultures. The non-polyene antifungal compounds actiphenol and surugamide A were also identified. The findings indicate that the ability of Streptomyces to produce cytolytic compounds (here manifested by hemolysis on blood agar) is an intrinsic feature of the bacteria in the soil environment and could even serve as a virulence factor when colonizing available host organisms. Additionally, a literature review of polyenes and non-polyene hemolytic metabolites produced by Streptomyces is presented.

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