Phage diversity in cell-free DNA identifies bacterial pathogens in human sepsis cases.

Autor: Haddock NL; Immunology Program, School of Medicine, Stanford University, Stanford, CA, USA., Barkal LJ; Division of Pulmonary, Allergy, and Critical Care Medicine, School of Medicine, Stanford University, Stanford, CA, USA., Ram-Mohan N; Department of Emergency Medicine, School of Medicine, Stanford University, Stanford, CA, USA., Kaber G; Department of Pediatrics, School of Medicine, Stanford University, Stanford, CA, USA., Chiu CY; Department of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, CA, USA., Bhatt AS; Division of Hematology, School of Medicine, Stanford University, Stanford, CA, USA.; Department of Genetics, Stanford University, Stanford, CA, USA., Yang S; Department of Emergency Medicine, School of Medicine, Stanford University, Stanford, CA, USA., Bollyky PL; Division of Infectious Diseases and Geographic Medicine, School of Medicine, Stanford University, Stanford, CA, USA. pbollyky@stanford.edu.
Jazyk: angličtina
Zdroj: Nature microbiology [Nat Microbiol] 2023 Aug; Vol. 8 (8), pp. 1495-1507. Date of Electronic Publication: 2023 Jun 12.
DOI: 10.1038/s41564-023-01406-x
Abstrakt: Bacteriophages, viruses that infect bacteria, have great specificity for their bacterial hosts at the strain and species level. However, the relationship between the phageome and associated bacterial population dynamics is unclear. Here we generated a computational pipeline to identify sequences associated with bacteriophages and their bacterial hosts in cell-free DNA from plasma samples. Analysis of two independent cohorts, including a Stanford Cohort of 61 septic patients and 10 controls and the SeqStudy cohort of 224 septic patients and 167 controls, reveals a circulating phageome in the plasma of all sampled individuals. Moreover, infection is associated with overrepresentation of pathogen-specific phages, allowing for identification of bacterial pathogens. We find that information on phage diversity enables identification of the bacteria that produced these phages, including pathovariant strains of Escherichia coli. Phage sequences can likewise be used to distinguish between closely related bacterial species such as Staphylococcus aureus, a frequent pathogen, and coagulase-negative Staphylococcus, a frequent contaminant. Phage cell-free DNA may have utility in studying bacterial infections.
(© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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