Draft Genome Sequences of Five Novel Polyketide Synthetase-Containing Mouse Escherichia coli Strains

Mannion, Anthony; Shen, Zeli; Feng, Yan; García, Alexis; Fox, James G.

doi:10.1128/genomea.01082-16

Cited by 1 publication

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“…Previously, we reported the draft genomes of two E . coli isolates from this study that were recovered from the blood of mice (accession numbers 1512290008 and 1512290026)[ 24 ]. Both genomes contained a complete ~54-kb PKS pathogenicity island required for colibactin synthesis[ 24 ].…”

Section: Discussionmentioning

confidence: 99%

“…coli isolates from this study that were recovered from the blood of mice (accession numbers 1512290008 and 1512290026)[ 24 ]. Both genomes contained a complete ~54-kb PKS pathogenicity island required for colibactin synthesis[ 24 ]. Cytolethal distending toxin ( cdt ), cytotoxic necrotizing factor ( cnf ), and cycle inhibiting factor ( cif ) genes known to cause megalocytosis were not present in either of these genomes, which substantiated our PCR results, suggesting the megalocytic cytotoxicity observed in our in vitro infection experiments was the result of colibactin activity.…”

Section: Discussionmentioning

confidence: 99%

“…E . coli strains used for cytotoxicity assay included K12 (negative control), NC101 (colibactin positive control), and novel mouse isolates 1512290008 [ 24 ], 1512290026 [ 24 ], 1601050009, and 1601060011. The cell culture assay for colibactin cytotoxicity was performed as described previously with modifications [ 5 ].…”

Section: Methodsmentioning

confidence: 99%

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Cytotoxic Escherichia coli strains encoding colibactin isolated from immunocompromised mice with urosepsis and meningitis

et al. 2018

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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 Wsh/Wsh 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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%