scholarly journals Structure and diversity of urinary cell-free DNA informative of host-pathogen interactions in human urinary tract infection

2017 ◽  
Author(s):  
Philip Burnham ◽  
Darshana Dadhania ◽  
Michael Heyang ◽  
Fanny Chen ◽  
Lars F. Westblade ◽  
...  

AbstractInfections of the urinary tract are the most common form of infection in the human population. Here, we tested the utility of urinary cell-free DNA (cfDNA) to comprehensively monitor host and pathogen dynamics in the scope of bacterial and viral urinary tract infections. We assayed cfDNA isolated from 141 urine samples obtained from a cohort of 82 kidney transplant recipients by next-generation sequencing. We find that urinary cfDNA simultaneously informs about the composition of the bacterial and viral components of the microbiome, antimicrobial susceptibility, bacterial growth dynamics, kidney allograft injury, and the host response to infection. These different layers of information are accessible from a single assay and individually agree with corresponding clinical tests based on quantitative PCR, conventional bacterial culture, and urinalysis. In addition, cfDNA reveals the frequent occurrence of pathologies that remain undiagnosed in conventional diagnostic workups. Our work identifies urinary cfDNA as a highly versatile tool to monitor infections of the urinary tract.

2006 ◽  
Author(s):  
Abdulmalik M Alkatheri ◽  
Ali Hajeer ◽  
Hanan Al Kadri ◽  
Majed Al-Jeraisy ◽  
Abullah Alsayyari

2019 ◽  
Vol 103 (6) ◽  
pp. 1272-1276 ◽  
Author(s):  
Thijs ten Doesschate ◽  
Henri van Werkhoven ◽  
Sabine Meijvis ◽  
Janneke Stalenhoef ◽  
Arjan van Zuilen ◽  
...  

2019 ◽  
Vol 19 (6) ◽  
pp. 1663-1670 ◽  
Author(s):  
Edmund Huang ◽  
Supreet Sethi ◽  
Alice Peng ◽  
Reiad Najjar ◽  
James Mirocha ◽  
...  

2019 ◽  
Author(s):  
Alexandre Pellan Cheng ◽  
Philip Burnham ◽  
John Richard Lee ◽  
Matthew Pellan Cheng ◽  
Manikkam Suthanthiran ◽  
...  

ABSTRACTHigh-throughput metagenomic sequencing offers an unbiased approach to identify pathogens in clinical samples. Conventional metagenomic sequencing however does not integrate information about the host, which is often critical to distinguish infection from infectious disease, and to assess the severity of disease. Here, we explore the utility of high-throughput sequencing of cell-free DNA after bisulfite conversion to map the tissue and cell types of origin of host-derived cell-free DNA, and to profile the bacterial and viral metagenome. We applied this assay to 51 urinary cfDNA isolates collected from a cohort of kidney transplant recipients with and without bacterial and viral infection of the urinary tract. We find that the cell and tissue types of origin of urinary cell-free DNA can be derived from its genome-wide profile of methylation marks, and strongly depend on infection status. We find evidence of kidney and bladder tissue damage due to viral and bacterial infection, respectively, and of the recruitment of neutrophils to the urinary tract during infection. Through direct comparison to conventional metagenomic sequencing as well as clinical tests of infection, we find this assay accurately captures the bacterial and viral composition of the sample. The assay presented here is straightforward to implement, offers a systems view into bacterial and viral infections of the urinary tract, and can find future use as a tool for the differential diagnosis of infections.


2020 ◽  
Vol 104 (S3) ◽  
pp. S367-S368
Author(s):  
Gang Huang ◽  
Xu-Tao Chen ◽  
Wen-Fang Chen ◽  
Pei-Song Chen ◽  
Ting-Ya Jiang ◽  
...  

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