A Human Lung-Associated Streptomyces sp. TR1341 Produces Various Secondary Metabolites Responsible for Virulence, Cytotoxicity and Modulation of Immune Response

Abstract

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.

Dysbiotic Gut Microbiota and Dysregulation of Cytokine Profile in Children and Teens With Autism Spectrum Disorder

“…Among the identified pathogenic taxa, several species of the Proteus and Neisseria genera are known human pathogens that can induce diseases such as meningitis and urinary tract infections. Streptomyces and Desulfovibrio have been well documented in inducing inflammatory diseases and have been shown to produce toxic, pro-inflammatory compounds as secondary metabolites ( Finegold et al, 2010 ; Herbrík et al, 2020 ). Containing more than 500 species, the colonization of Streptomyces within the human gut has been scarcely reported and evidence of its detection within that of ASD individuals has not been previously described.…”

Chemical entrapment and killing of insects by bacteria

“…They have no genes that are homologous to known virulence determinants or pathogenicity islands (57)(58)(59). Indeed, the existing literature on interactions between streptomycetes and higher eukaryotes indicates that they are either benign substituents of their microbiomes (60,61) or, in the case of many insects, highly bene cial mutualists (21)(22)(23).…”

Inhibition of Pro-Inflammatory Cytokines by Metabolites of Streptomycetes—A Potential Alternative to Current Anti-Inflammatory Drugs?

“…The last two were isolated in our laboratory from the cultures of producer streptomycete strains. Based on our previous observation, cytokines IL-1β and TNF-α are the most sensitive markers reflecting downregulation of inflammation using THP-1 cell line in our experimental setup [15]. Therefore, the capacity of manumycin-type metabolites to suppress both gene expression and secretion of IL-1β and TNF-α has been tested.…”

“…Though the effort to find a reliable treatment of inflammatory diseases is immense, breaking news on a universal drug with only mild side-effects are still missing. Currently, most of the clinically downregulation of inflammation using THP-1 cell line in our experimental setup [15]. Therefore, the capacity of manumycin-type metabolites to suppress both gene expression and secretion of IL-1β and TNF-α has been tested.…”