title: Murine model of chemotherapy-induced extraintestinal pathogenic Escherichia coli translocation.
abstract: Escherichia coli is a major cause of life-threatening infections in patients with neutropenia, particularly those receiving chemotherapy for the treatment of cancer. In most cases, these infections originate from opportunistic strains living within the patient's gastrointestinal tract which then translocate to major organ systems. There are no animal models that faithfully recapitulate these infections, and, as such, the host or bacterial factors that govern this process remain unidentified. We present here a novel model of chemotherapy-induced bacterial translocation of E. coli. Oral gavage of BALB/c mice with a clinical isolate of extraintestinal pathogenic E. coli (ExPEC) leads to stable and long-term colonization of the murine intestine. Following the induction of neutropenia with the chemotherapeutic drug cyclophosphamide, ExPEC translocates from the intestine to the lungs, liver, spleen, and kidneys with concomitant morbidity in infected animals. Translocation can also occur in mice bearing mammary tumors, even in the absence of chemotherapy. Translocation of ExPEC is also associated with an increase of the diversity of bacterial DNA detected in the blood. This is the first report of a chemotherapy-based animal model of ExPEC translocation in cancerous mice, a system that can be readily used to identify important virulence factors for this process.
authors.affiliation: Molecular Virology and Microbiology Department, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Sabrina I
authors.initials: SI
authors.lastname: Green
authors.affiliation: Molecular Virology and Microbiology Department, Baylor College of Medicine, Houston, Texas, USA The Alkek Center for Metagenomics and Microbiome Research at Baylor College of Medicine, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Nadim J
authors.initials: NJ
authors.lastname: Ajami
authors.affiliation: Molecular Virology and Microbiology Department, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.affiliation: Molecular Virology and Microbiology Department, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Nina M
authors.initials: NM
authors.lastname: Poole
authors.affiliation: Comparative Pathology Laboratory of the Center for Comparative Medicine at Baylor College of Medicine, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Roger E
authors.initials: RE
authors.lastname: Price
authors.affiliation: Molecular Virology and Microbiology Department, Baylor College of Medicine, Houston, Texas, USA The Alkek Center for Metagenomics and Microbiome Research at Baylor College of Medicine, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Petrosino
authors.affiliation: Molecular Virology and Microbiology Department, Baylor College of Medicine, Houston, Texas, USA maresso@bcm.edu.
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Maresso
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D018988:Bacterial Translocation; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000235:genetics / Q000502:physiology*; D004927:Escherichia coli Infections / Q000209:etiology / Q000382:microbiology*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007422:Intestines / Q000382:microbiology*; D008168:Lung / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy*; D009503:Neutropenia / Q000150:complications / Q000188:drug therapy
chemical_list: D000970:Antineoplastic Agents; D029968:Escherichia coli Proteins