Sequence-based discovery of Bradyrhizobium enterica in cord colitis syndrome. N Engl J Med 2013 Aug 08;369(6):517-28
Date
08/09/2013Pubmed ID
23924002Pubmed Central ID
PMC3889161DOI
10.1056/NEJMoa1211115Abstract
BACKGROUND: Immunosuppression is associated with a variety of idiopathic clinical syndromes that may have infectious causes. It has been hypothesized that the cord colitis syndrome, a complication of umbilical-cord hematopoietic stem-cell transplantation, is infectious in origin.
METHODS: We performed shotgun DNA sequencing on four archived, paraffin-embedded endoscopic colon-biopsy specimens obtained from two patients with cord colitis. Computational subtraction of human and known microbial sequences and assembly of residual sequences into a bacterial draft genome were performed. We used polymerase-chain-reaction (PCR) assays and fluorescence in situ hybridization to determine whether the corresponding bacterium was present in additional patients and controls.
RESULTS: DNA sequencing of the biopsy specimens revealed more than 2.5 million sequencing reads that did not match known organisms. These sequences were computationally assembled into a 7.65-Mb draft genome showing a high degree of homology with genomes of bacteria in the bradyrhizobium genus. The corresponding newly discovered bacterium was provisionally named Bradyrhizobium enterica. PCR identified B. enterica nucleotide sequences in biopsy specimens from all three additional patients with cord colitis whose samples were tested, whereas B. enterica sequences were absent in samples obtained from healthy controls and patients with colon cancer or graft-versus-host disease.
CONCLUSIONS: We assembled a novel bacterial draft genome from the direct sequencing of tissue specimens from patients with cord colitis. Association of these sequences with cord colitis suggests that B. enterica may be an opportunistic human pathogen. (Funded by the National Cancer Institute and others.)
Author List
Bhatt AS, Freeman SS, Herrera AF, Pedamallu CS, Gevers D, Duke F, Jung J, Michaud M, Walker BJ, Young S, Earl AM, Kostic AD, Ojesina AI, Hasserjian R, Ballen KK, Chen YB, Hobbs G, Antin JH, Soiffer RJ, Baden LR, Garrett WS, Hornick JL, Marty FM, Meyerson MAuthor
Akinyemi Ojesina MD, PhD Assistant Professor in the Obstetrics and Gynecology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
BiopsyBradyrhizobium
Colitis
Colon
Colonic Neoplasms
DNA, Bacterial
Diarrhea
Female
Fetal Blood
Genome, Bacterial
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Humans
Immunocompromised Host
Male
Opportunistic Infections
Paraffin Embedding
Phylogeny
Polymerase Chain Reaction
Sequence Analysis, DNA
