Abstract
The DNA phosphorothioate (PT) modification existing in many prokaryotes, including bacterial pathogens and commensals, confers multiple characteristics, including restricting gene transfer, influencing the global transcriptional response, and reducing fitness during exposure to chemical mediators of inflammation. While PT-containing bacteria have been investigated in a variety of environments, they have not been studied in the human microbiome. Here, we investigated the distribution of PT-harboring strains and verified their existence in the human microbiome. We found over 2000 PT gene-containing strains distributed in different body sites, especially in the gastrointestinal tract. PT-modifying genes are preferentially distributed within several genera, including Pseudomonas, Clostridioides, and Escherichia, with phylogenic diversities. We also assessed the PT modification patterns and found six new PT-linked dinucleotides (CpsG, CpsT, ApsG, TpsG, GpsC, ApsT) in human fecal DNA. To further investigate the PT in the human gut microbiome, we analyzed the abundance of PT-modifying genes and quantified the PT-linked dinucleotides in the fecal DNA. These results confirmed that human microbiome is a rich reservoir for PT-containing microbes and contains a wide variety of PT modification patterns.
Highlights
Phosphorothioate (PT) DNA modifications, in which the nonbridging oxygen in the phosphate backbone is replaced by sulfur, are widespread among bacteria and archaea [1]
We performed an informatic analysis of sequenced microbiome-related genomes and a mass spectrometric analysis of fecal DNA to show the widespread presence of PT-modifying genes and PT-linked dinucleotides in the human microbiome
We searched for PT-modifying genes in over 40,000 bacterial genomes under the human microbiome category from websites
Summary
Phosphorothioate (PT) DNA modifications, in which the nonbridging oxygen in the phosphate backbone is replaced by sulfur, are widespread among bacteria and archaea [1]. The PT-modifying gene cluster, dndA-E, has been found in more than 1300 sequenced genomes [2] and confers cells with 5 -GpsAAC-3 /5 -GpsTTC-3 or 5 -GpsGCC-3 consensus sequences [3]. Another PT-modifying gene cluster has been reported, sspA-D, which confers cells with 5 -CpsCA-3 on the single strand [4]. We performed an informatic analysis of sequenced microbiome-related genomes and a mass spectrometric analysis of fecal DNA to show the widespread presence of PT-modifying genes and PT-linked dinucleotides in the human microbiome
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