title: TraJ-dependent Escherichia coli K1 interactions with professional phagocytes are important for early systemic dissemination of infection in the neonatal rat.
abstract: Escherichia coli is a major cause of neonatal bacterial sepsis and meningitis. We recently identified a gene, traJ, which contributes to the ability of E. coli K1 to penetrate the blood-brain barrier in the neonatal rat. Because very little is known regarding the most critical step in disease progression, translocation to the gut and dissemination to the lymphoid tissues after a natural route of infection, we assessed the ability of a traJ mutant to cause systemic disease in the neonatal rat. Our studies determined that the traJ mutant is significantly less virulent than the wild type in the neonatal rat due to a decreased ability to disseminate from the mesenteric lymph nodes to the deeper tissues of the liver and spleen and to the blood during the early stages of systemic disease. Histopathologic studies determined that although significantly less or no mutant bacteria were recovered from the spleen and livers of infected neonatal rats, the inflammatory response was considerably greater than that in wild-type-colonized tissues. In vitro studies revealed that macrophages internalize the traJ mutant less frequently than they do the wild type and by a morphologically distinct process. Furthermore, we determined that tissue macrophages and dendritic cells within the liver and spleen are the major cellular targets of E. coli K1 and that TraJ significantly contributes to the predominantly intracellular nature of E. coli K1 within these professional phagocytes exclusively during the early stages of systemic disease. These data indicate that, contrary to earlier indications, E. coli K1 resides within professional phagocytes, and this is essential for the efficient progression of systemic disease.
authors.affiliation: Department of Pathology, Childrens Hospital Los Angeles, Los Angeles, California 90027, USA.
authors.forename: Val T
authors.initials: VT
authors.lastname: Hill
authors.forename: Stacy M
authors.initials: SM
authors.lastname: Townsend
authors.forename: Robyn S
authors.initials: RS
authors.lastname: Arias
authors.forename: Jasmine M
authors.initials: JM
authors.lastname: Jenabi
authors.forename: Ignacio
authors.initials: I
authors.lastname: Gomez-Gonzalez
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Shimada
authors.forename: Julie L
authors.initials: JL
authors.lastname: Badger
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000276:immunology* / Q000382:microbiology / Q000503:physiopathology*; D029968:Escherichia coli Proteins; D006801:Humans; D008099:Liver / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000382:microbiology; D020556:Neutrophil Infiltration; D010586:Phagocytes / Q000382:microbiology*; D010587:Phagocytosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000276:immunology; D020298:U937 Cells; D014774:Virulence
chemical_list: D001425:Bacterial Outer Membrane Proteins; D029968:Escherichia coli Proteins; C488999:TraJ protein, E coli; C041427:TraJ protein, bacteria