Cytotoxic Escherichia coli strains encoding colibactin isolated from immunocompromised mice with urosepsis and meningitis
Name
journal.pone.0194443.pdf
Size
13.98 MB
Format
Adobe PDF
Checksum (MD5)
9e73014ad837250ca1a2a9b30d02f560
Author(s)
Wert, Katherine J.
Jacobsen, Johanne T.
Victora, Gabriel
Jaenisch, Rudolf
Bakthavatchalu, Vasudevan
Feng, Yan
Mannion, Anthony
Ge, Zhongming
Garcia, Alexis
Scott, Kathleen
Date Issued
March 2018
Journal
PLOS ONE
Publisher
Public Library of Science
Citation
Bakthavatchalu, Vasudevan et al. “Cytotoxic Escherichia Coli Strains Encoding Colibactin Isolated from Immunocompromised Mice with Urosepsis and Meningitis.” Edited by Paulo Lee Ho. PLOS ONE 13, 3 (March 2018): e0194443 © 2018 Bakthavatchalu et al
Version
Final published version
Abstract
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Immune-compromised mouse models allow for testing the preclinical efficacy of human cell transplantations and gene therapy strategies before moving forward to clinical trials. However, CRISPR/Cas9 gene editing of the W sh /W sh mouse strain to create an immune-compromised model lacking function of Rag2 and Il2rγ led to unexpected morbidity and mortality. This warranted an investigation to ascertain the cause and predisposing factors associated with the outbreak. Postmortem examination was performed on 15 moribund mice. The main lesions observed in these mice consisted of ascending urogenital tract infections, suppurative otitis media, pneumonia, myocarditis, and meningoencephalomyelitis. As Escherichia coli strains harboring polyketide synthase (pks) genomic island were recently isolated from laboratory mice, the tissue sections from the urogenital tract, heart, and middle ear were subjected to E. coli specific PNA-FISH assay that revealed discrete colonies of E. coli associated with the lesions. Microbiological examination and 16S rRNA sequencing confirmed E. coli-induced infection and septicemia in the affected mice. Further characterization by clb gene analysis and colibactin toxicity assays of the pks+ E. coli revealed colibactin-associated cytotoxicity. Rederivation of the transgenic mice using embryo transfer produced mice with an intestinal flora devoid of pks+ E. coli. Importantly, these barrier-maintained rederived mice have produced multiple litters without adverse health effects. This report is the first to describe acute morbidity and mortality associated with pks+ E. coli urosepsis and meningitis in immunocompromised mice, and highlights the importance of monitoring and exclusion of colibactin-producing pks+ E. coli.
MIT Department
Massachusetts Institute of Technology. Division of Comparative Medicine
Terms of Use
Creative Commons Attribution 4.0 International License
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DOI of Published Version
http://dx.doi.org/10.1371/journal.pone.0194443
