Abstract

Streptomyces sp. TR1341 was isolated from the sputum of a man with a history of lung and kidney tuberculosis, recurrent respiratory infections, and COPD. It produces secondary metabolites associated with cytotoxicity and immune response modulation. In this study, we complement our previous results by identifying the genetic features associated with the production of these secondary metabolites and other characteristics that could benefit the strain during its colonization of human tissues (virulence factors, modification of the host immune response, or the production of siderophores). We performed a comparative phylogenetic analysis to identify the genetic features that are shared by environmental isolates and human respiratory pathogens. The results showed a high genomic similarity of Streptomyces sp. TR1341 to the plant-associated Streptomyces sp. endophyte_N2, inferring a soil origin of the strain. Putative virulence genes, such as mammalian cell entry (mce) genes were not detected in the TR1341’s genome. The presence of a type VII secretion system, distinct from the ones found in Mycobacterium species, suggests a different colonization strategy than the one used by other actinomycete lung pathogens. We identified a higher diversity of genes related to iron acquisition and demonstrated that the strain produces ferrioxamine B in vitro. These results indicate that TR1341 may have an advantage in colonizing environments that are low in iron, such as human tissue.

Highlights

  • In our previous study we showed that TR1341’s antifungal, β-hemolytic, and cytolytic activities were due to the production of filipin III and fungichromin, and the antibacterial and cytotoxic activities were due to the production of actinomycin X2

  • TR1341 was isolated from the sputum of an elderly man, who was treated for several respiratory tract-related diseases for decades

  • The filipin Biosynthetic gene clusters (BGC) is similar to the one characterized in Streptomyces avermitilis NRRL 8165 [86] and Streptomyces filipinensis DSM 40112 [87], from which it was first isolated as an antifungal agent [88]

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Summary

Introduction

Studies on Streptomyces scabies and Streptomyces coelicolor proved that their ESX system seems to be involved in sporulation and development rather than virulence [43,44] Another important colonization mechanism is mediated by mammalian cell entry (MCE) proteins. TR1341 has a potentially better adaptation strategy to the human tissue niche which involves the production of specific secondary metabolites, or other abovementioned colonization mechanisms. These mechanisms give TR1341 an edge over other environmental strain

Materials and Methods
Morphological Characteristics and Microscopy
Growth Curve and Carbon Utilization Assay
Siderophore Production and Identification
Dataset
Orthologous Genes and Species Tree Inference
Biosynthetic Gene Clusters
Results and Discussion
Phylogenetic tree based on orthologousfamilies families calculated with
Biosynthetic predicted by grey
Conclusions
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