Involvement of the DNA Phosphorothioation System in TorR Binding and Anaerobic TMAO Respiration in Salmonella enterica

Tang, You‐Zhi; Hong, Yue; Liu, Li; Du, Xiaolong; Ren, Yanling; Jiang, Shu‐Heng; Liu, Wanjing; Chen, Chao; Deng, Zixin; Wang, Lianrong; Shi, Chen

doi:10.1128/mbio.00699-22

Cited by 5 publications

(6 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1 , Supplementary Table S3 ). These evolutionary co-occurrences likely reflect a fitness advantage, such as that observed for the presence of Dnd and Ssp together, which provides complementary and synergistic protection against temperate and lytic phages as well as phage induction 46 . The co-occurrence of combinations of all three established PT systems and two putative systems in Cyanobacteria supports the hypothesis of an evolutionary divergence that may originate from a sulfur-based metabolism in ancient Cyanobacteria ancestor 9 .…”

Section: Discussionmentioning

confidence: 99%

Phosphorothioate DNA modification by BREX Type 4 systems in the human gut microbiome

Yuan,

DeMott,

Byrne

et al. 2024

Preprint

View full text Add to dashboard Cite

Among dozens of microbial DNA modifications regulating gene expression and host defense, phosphorothioation (PT) is the only known backbone modification, with sulfur inserted at a non-bridging oxygen bydndandsspgene families. Here we explored the distribution of PT genes in 13,663 human gut microbiome genomes, finding that 6.3% possesseddndorsspgenes predominantly in Bacillota, Bacteroidota, and Pseudomonadota. This analysis uncovered several putative new PT synthesis systems, including Type 4 Bacteriophage Exclusion (BREX)brxgenes, which were genetically validated inBacteroides salyersiae.Mass spectrometric analysis of DNA from 226 gut microbiome isolates possessingdnd,ssp, andbrxgenes revealed 8 PT dinucleotide settings confirmed in 6 consensus sequences by PT-specific DNA sequencing. Genomic analysis showed PT enrichment in rRNA genes and depletion at gene boundaries. These results illustrate the power of the microbiome for discovering prokaryotic epigenetics and the widespread distribution of oxidation-sensitive PTs in gut microbes.One-sentence SummaryApplication of informatic, mass spectrometric, and sequencing-based mapping tools to human gut bacteria revealed new phosphorothioate epigenetic systems widespread in the gut microbiome.

show abstract

Section: Discussionmentioning

confidence: 99%

Phosphorothioate DNA modification by BREX Type 4 systems in the human gut microbiome

Yuan,

DeMott,

Byrne

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…3, Table S4), presumably due to the low detection power of the modification type using current SMRT technology. In addition to methylation, other epigenetic modifications, such as phosphorothioate modification, have recently been reported to play a significant role in phage defense (58). To better understand epigenomic functions, further methodological developments to measure a wide variety of DNA modifications are required.…”

Section: Discussionmentioning

confidence: 99%

Host-encoded DNA methyltransferases modify the epigenome and host tropism of invading phages

Takahashi,

Hiraoka,

Matsumoto

et al. 2024

Preprint

View full text Add to dashboard Cite

A part of prokaryotic DNA methyltransferases (MTases) is associated with phage-defense systems (e.g., restriction-modification [RM] system) to combat the invasion of foreign DNA (e.g., phages). To date, the epigenomes of host and phage during the infection cycle have not been directly observed, and their association with phage infection efficiency remains unclear. Here, using the wide-host-range phage KHP30T and three Helicobacter pylori strains (26695, 3401T, and HPK5) that possess different sets of MTases, we investigated changes in infection efficiency and epigenomes of the phage via adaptation to each host strain. Based on the designed multi-stage infection flow, adapted phages showed higher titers only against the last infected H. pylori strain, suggesting an attendant change in host tropism. Using single-molecule real-time sequencing, we retrieved each complete genome and 15 and 20 methylated motifs from H. pylori 3401T and HPK5, respectively. In general, the methylated motifs were common between pairs of adapted phages and the last infected host strain. Some exceptions were identified that may arise from phase variation. Our results demonstrate phage genomes are methylated by host-encoded MTases during the infection cycle as they pass through the host RM system, resulting in increased infection efficiency of phages against the same host strain.

show abstract

“…Being a facultative anaerobe, Salmonella can reprogram its respiratory pathway during the transition from an ambient to an oxygen‐deficient environment. In the hypoxic environment of the mammalian gut, Salmonella can utilize inflammatory byproducts like nitrate, tetrathionate, dimethyl sulfoxide, and trimethyl ammonium oxide as electron acceptors during anaerobic respiration [39–41]. In this aspect, nitrate is the earliest electron acceptor that undergoes reduction by nitrate reductase enzyme via the NarX/L regulatory system [15].…”

Section: Discussionmentioning

confidence: 99%

Role of narL gene in the pathogenesis of Salmonella Typhimurium

Mani,

Priyadarsini,

K. Channabasappa

et al. 2023

J Basic Microbiol

View full text Add to dashboard Cite

Salmonella Typhimurium (STM) is a facultative anaerobe and one of the causative agents of nontyphoidal salmonellosis (NTS). Its anaerobic metabolism is enabled under the hypoxic environment that is encountered inside macrophages and the gut lumen of the host. In both of these niches, free radicals and oxidative intermediates are released by neutrophils as an inflammatory response. These chemical species further undergo reactions to produce nitrate, which is preferably taken up by STM as an electron acceptor in the absence of oxygen. NarL, the response regulator of the two‐component regulatory system NarX/L, and a transcription factor, gets activated under anaerobic nitrate‐rich conditions and upregulates the nitrate reduction during anaerobic respiration of STM. To understand the role of NarL in the pathogenesis of STM, we generated a narL‐knockout (STM:ΔnarL) as well as a narL‐complemented strain of STM. Anaerobically, the mutant displayed no growth defect but a significant attenuation in the swimming (26%) and swarming (61%) motility, and biofilm‐forming ability (73%) in vitro, while these morphotypes got rescued upon genetic complementation. We also observed a downregulation in the expression of genes associated with nitrate reduction (narG) and biofilm formation (csgA and csgD) in anaerobically grown STM:ΔnarL. As compared with wild STM, narL mutant exhibited a threefold reduction in the intracellular replication in both intestinal epithelial cells (INT‐ 407) and monocyte‐derived macrophages of poultry origin. Further, in vivo competitive assay in the liver and spleen of the murine model showed a competitive index of 0.48 ± 0.58 and 0.403668 ± 0.32, respectively, for STM:ΔnarL.

show abstract

Involvement of the DNA Phosphorothioation System in TorR Binding and Anaerobic TMAO Respiration in Salmonella enterica

Cited by 5 publications

References 77 publications

Phosphorothioate DNA modification by BREX Type 4 systems in the human gut microbiome

Phosphorothioate DNA modification by BREX Type 4 systems in the human gut microbiome

Host-encoded DNA methyltransferases modify the epigenome and host tropism of invading phages

Role of narL gene in the pathogenesis of Salmonella Typhimurium

Contact Info

Product

Resources

About