title: Cytotoxic Escherichia coli strains encoding colibactin colonize laboratory mice.
abstract: Escherichia coli strains have not been fully characterized in laboratory mice and are not currently excluded from mouse colonies. Colibactin (Clb), a cytotoxin, has been associated with inflammation and cancer in humans and animals. We performed bacterial cultures utilizing rectal swab, fecal, and extra intestinal samples from clinically unaffected or affected laboratory mice. Fifty-one E. coli were isolated from 45 laboratory mice, identified biochemically, and selected isolates were serotyped. The 16S rRNA gene was amplified and sequenced for specific isolates, PCR used for clbA and clbQ gene amplification, and phylogenetic group identification was performed on all 51 E. coli strains. Clb genes were sequenced and selected E. coli isolates were characterized using a HeLa cell cytotoxicity assay. Forty-five of the 51 E. coli isolates (88%) encoded clbA and clbQ and belonged to phylogenetic group B2. Mouse E. coli serotypes included: O2:H6, O-:H-, OM:H+, and O22:H-. Clb-encoding O2: H6 mouse E. coli isolates were cytotoxic in vitro. A Clb-encoding E. coli was isolated from a clinically affected genetically modified mouse with cystic endometrial hyperplasia. Our findings suggest that Clb-encoding E. coli colonize laboratory mice and may induce clinical and subclinical diseases that may impact experimental mouse models.
authors.affiliation: Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: Alexis
authors.initials: A
authors.lastname: García
authors.affiliation: Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Mannion
authors.affiliation: Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Madden
authors.affiliation: Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: Vasudevan
authors.initials: V
authors.lastname: Bakthavatchalu
authors.affiliation: Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: Zeli
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Ge
authors.affiliation: Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. Electronic address: jgfox@mit.edu.
authors.forename: James G
authors.initials: JG
authors.lastname: Fox
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D016000:Cluster Analysis; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D004275:DNA, Ribosomal / Q000737:chemistry / Q000235:genetics; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D004926:Escherichia coli / Q000145:classification / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D010455:Peptides / Q000235:genetics / Q000378:metabolism* / Q000633:toxicity; D010802:Phylogeny; D061065:Polyketides / Q000378:metabolism* / Q000633:toxicity; D016133:Polymerase Chain Reaction; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D017422:Sequence Analysis, DNA; D012703:Serotyping
chemical_list: D004269:DNA, Bacterial; D004275:DNA, Ribosomal; D010455:Peptides; D061065:Polyketides; D012336:RNA, Ribosomal, 16S; C569566:colibactin
keywords: Cancer; Colibactin; Cytotoxic; Disease; Escherichia coli; Mice