Streptomyces sp. BI87 from human gut: potent anticancer activities and divergence from known Streptomyces lineages

ABSTRACT Cancer is among the deadliest diseases with few truly curative therapies. Recent studies have shown that the human intestinal microbiota contains bacteria that exhibit potent suppressive effects on cancer or coordinate anticancer functions with the immune system. However, whether the peculiar anticancer trait was acquired stochastically by a strain of a non-anticancer bacterial species or an intrinsic property of a phylogenetic lineage of bacteria remained unclear. In this study, we compared a human gut isolate Streptomyces sp. BI87, which had highly effective anticancer activities, with the type strain of Streptomyces albidoflavus , DSM 40455 T , which was most closely related to BI87 among 30 type strains of the genus Streptomyces but did not show any detectable anticancer activities. We found that, although BI87 and DSM 40455 T had >99% 16S rDNA sequence similarity, they are phylogenetically separated by a genetic boundary into distinct natural species as evaluated by the 3Cs definition of bacterial species based on the ratio of common genes with zero sequence degeneracy. In addition to the anticancer activities, BI87 encodes several biological characteristics different from DSM 40455 T , including those of antibacterial and antiviral spectra, secondary metabolites, structural composition in the cell wall, and major cellular fatty acids. Based on the genomic and phenotypic distinctions of BI87 from closely related Streptomyces strains, we propose that the anticancer bacterial strain BI87 represents a new lineage at the natural species level within the genus Streptomyces . IMPORTANCE The characterization of the anticancer bacterial strain, Streptomyces sp . BI87, isolated from a healthy human, suggests the prevalent existence of anticancer microbes in the gut microbiome of humans, which may be nurtured and harnessed for cancer prevention or treatment without the need for the introduction of engineered and non-indigenous microbes to a person or the use of radio- or chemo-therapies. Also important is the finding that a close relative of BI87, Streptomyces albidoflavus DSM40455 T , does not express appreciable anticancer properties in the same in vitro and in vivo experiments, demonstrating that Streptomyces sp. BI87 represents a novel bacterial lineage with selective suppressive activities on cancer, at the phylogenetic level of natural species. Genomic comparisons between BI87 and DSM40455 T demonstrate that phylogenetic delineation of closely related bacteria needs to be conducted at the level of natural species rather than OTUs, as an OTU may contain phenotypically or even phylogenetically radically distinct bacteria.