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.

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