Viral dark matter exposed: metagenome database detects phage-derived antibacterial enzyme

In a pioneer study published in Cell Host & Microbe – Researchers at Osaka City University and The Institute for Medical Science, The University of Tokyo, reported intestinal bacterial and viral metagenome information from the fecal samples of 101 healthy Japanese individuals. This analysis, leveraging host bacteria–phage associations, detected phage-derived antibacterial enzymes that control pathobionts. As proof-of-concept, phage-derived endolysins are shown to regulate C. difficile infection in mice.

Abnormalities in the human intestinal microflora, known as dysbiosis, are connected tohave been implicated in various diseases. Altered microbial diversity and microbial substitution are frequently observed in dysbiosis, resulting in impairsment of the beneficial effects of host intestinal microflora, which causeon the host and disruption of homeostasis. Under dysbiosis, some symbiotic commensal bacteria to acquire virulence traits, proliferate, and become directly involved in the development and progression of disease. These bacteria are referred to as “pathobionts”, which are distinct from opportunistic pathogens.

C. difficile, which is a Gram-positive, spore-forming anaerobic bacterium, is a pathobiont andthat is the representative cause of nosocomial diarrhea following antibiotic treatment. Since antibiotic usage has the risk of killing beneficial bacteria and promoting dysbiosis, the development of methods to specifically manipulate intestinal pathobionts is essential for the treatment of dysbiosis-related diseases.

“Phages were sure to be applicable as a highly specific therapy for intestinal pathobiont elimination”, believed Professor Satoshi Uematsu. THowever, the infectious associations between phages and bacteria in the human intestine which is essential information for the development of phage therapies. Known as “viral dark matter” as they , had yet to be understood, fully elucidated. Therefore, researchers obtained intestinal bacterial and viral metagenome information about bacteria-phage associations from the fecal samples of 101 healthy individuals through the development of a virome analysis pipeline. Based on this information about host bacteria–phage associations, researchers screened C. difficile-specific phages and identified novel antibacterial enzymes, whose activity was confirmed both in vitro and in vivo.

“The accumulation of more metagenomic information on intestinal phages and bacteria will open up the possibility of developing treatments for a variety of dysbiosis-related diseases”, say Dr. Kosuke Fujimoto and Prof. Seiya Imoto.

Full bibliographic information

Uematsu, Satoshi et al.: "Metagenome Data on Intestinal Phage-Bacteria Associations Aids the Development of Phage Therapy Against Pathobionts", Cell Host & Microbe
Attached files
  • Phage-derived anti-bacterial enzyme attacks C. difficile © Satoshi Uematsu, Osaka City University (Illustration by Hideaki Miyauchi)

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