Dataset Information

Gut virome profiling identifies an association between temperate phages and colorectal cancer promoted by Helicobacter pylori infection.

ABSTRACT: Colorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide. While a close correlation between chronic Helicobacter pylori infection and CRC has been reported, the role of the virome has been overlooked. Here, we infected Apc-mutant mouse models and C57BL/6 mice with H. pylori and conducted a comprehensive metagenomics analysis of H. pylori-induced changes in lower gastrointestinal tract bacterial and viral communities. We observed an expansion of temperate phages in H. pylori infected Apc^+/1638N mice at the early stage of carcinogenesis. Some of the temperate phages were predicted to infect bacteria associated with CRC, including Enterococcus faecalis. We also observed a high prevalence of virulent genes, such as flgJ, cwlJ, and sleB, encoded by temperate phages. In addition, we identified phages associated with pre-onset and onset of H. pylori-promoted carcinogenesis. Through co-occurrence network analysis, we found strong associations between the viral and bacterial communities in infected mice before the onset of carcinogenesis. These findings suggest that the expansion of temperate phages, possibly caused by prophage induction triggered by H. pylori infection, may have contributed to the development of CRC in mice by interacting with the bacterial community.

SUBMITTER: Luo S

PROVIDER: S-EPMC10578192 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Gut virome profiling identifies an association between temperate phages and colorectal cancer promoted by Helicobacter pylori infection.

Luo Shiqi S Ru Jinlong J Mirzaei Mohammadali Khan MK Xue Jinling J Peng Xue X Ralser Anna A Mejías-Luque Raquel R Gerhard Markus M Deng Li L

Gut microbes 20230925 2

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide. While a close correlation between chronic Helicobacter pylori infection and CRC has been reported, the role of the virome has been overlooked. Here, we infected Apc-mutant mouse models and C57BL/6 mice with H. pylori and conducted a comprehensive metagenomics analysis of H. pylori-induced changes in lower gastrointestinal tract bacterial and viral communities. We observed an expansion of ...[more]

PMID: 37747149

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Project description:The development of gastrointestinal diseases has been found to be associated with Helicobacter pylori (H. pylori) infection and various biochemical stresses in stomach and intestine. These stresses, such as oxidative, osmotic and acid stresses, may bring about bi-directional effects on both hosts and H. pylori, leading to changes of protein expression in their proteomes. Therefore, proteins differentially expressed in H. pylori under various stresses not only reflect gastrointestinal environment but also provide useful biomarkers for disease diagnosis and prognosis. In this regard, proteomic technology is an ideal tool to identify potential biomarkers as it can systematically monitor proteins and protein variation on a large scale of cell's translational landscape, permitting in-depth analyses of host and pathogen interactions. By performing two-dimensional polyacrylamide gel electrophoresis (2-DE) followed by liquid chromatography-nanoESI-mass spectrometry (nanoLC-MS/MS), we have successfully pinpointed alkylhydroperoxide reductase (AhpC), neutrophil-activating protein and non-heme iron-binding ferritin as three prospective biomarkers showing up-regulation in H. pylori under oxidative, osmotic and acid stresses, respectively. Further biochemical characterization reveals that various environmental stresses can induce protein structure change and functional conversion in the identified biomarkers. Especially salient is the antioxidant enzyme AhpC, an abundant antioxidant protein present in H. pylori. It switches from a peroxide reductase of low-molecular-weight (LMW) oligomers to a molecular chaperone of high-molecular-weight (HMW) complexes under oxidative stress. Different seropositivy responses against LMW or HMW AhpC in H. pylori-infected patients faithfully match the disease progression from disease-free healthy persons to patients with gastric ulcer and cancer. These results has established AhpC of H. pylori as a promising diagnostic marker for gastrointestinal maladies, and highlight the utility of clinical proteomics for identifying disease biomarkers that can be uniquely applied to disease-oriented translational medicine.

Project description:Modern sequencing technologies have provided insight into the genetic diversity of numerous species, including the human pathogen Pseudomonas aeruginosa. Bacterial genomes often harbor bacteriophage genomes (prophages), which can account for upwards of 20% of the genome. Prior studies have found P. aeruginosa prophages that contribute to their host's pathogenicity and fitness. These advantages come in many different forms, including the production of toxins, promotion of biofilm formation, and displacement of other P. aeruginosa strains. While several different genera and species of P. aeruginosa prophages have been studied, there has not been a comprehensive study of the overall diversity of P. aeruginosa-infecting prophages. Here, we present the results of just such an analysis. A total of 6,852 high-confidence prophages were identified from 5,383 P. aeruginosa genomes from strains isolated from the human body and other environments. In total, 3,201 unique prophage sequences were identified. While 53.1% of these prophage sequences displayed sequence similarity to publicly available phage genomes, novel and highly mosaic prophages were discovered. Among these prophages, there is extensive diversity, including diversity within the functionally conserved integrase and C repressor coding regions, two genes responsible for prophage entering and persisting through the lysogenic life cycle. Analysis of integrase, C repressor, and terminase coding regions revealed extensive reassortment among P. aeruginosa prophages. This catalog of P. aeruginosa prophages provides a resource for future studies into the evolution of the species. IMPORTANCE Prophages play a critical role in the evolution of their host species and can also contribute to the virulence and fitness of pathogenic species. Here, we conducted a comprehensive investigation of prophage sequences from 5,383 publicly available Pseudomonas aeruginosa genomes from human as well as environmental isolates. We identified a diverse population of prophages, including tailed phages, inoviruses, and microviruses; 46.9% of the prophage sequences found share no significant sequence similarity with characterized phages, representing a vast array of novel P. aeruginosa-infecting phages. Our investigation into these prophages found substantial evidence of reassortment. In producing this, the first catalog of P. aeruginosa prophages, we uncovered both novel prophages as well as genetic content that have yet to be explored.

Dataset Information

Gut virome profiling identifies an association between temperate phages and colorectal cancer promoted by Helicobacter pylori infection.

Publications

Gut virome profiling identifies an association between temperate phages and colorectal cancer promoted by <i>Helicobacter pylori</i> infection.

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