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Infection and Immunity, January 2004, p. 478-488, Vol. 72, No. 1
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.1.478-488.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

TraJ-Dependent Escherichia coli K1 Interactions with Professional Phagocytes Are Important for Early Systemic Dissemination of Infection in the Neonatal Rat

Val T. Hill,1 Stacy M. Townsend,1 Robyn S. Arias,1,2 Jasmine M. Jenabi,1 Ignacio Gomez-Gonzalez,1,2 Hiroyuki Shimada,1,2 and Julie L. Badger1,2*

Department of Pathology, Childrens Hospital Los Angeles,1 University of Southern California School of Medicine, Los Angeles, California 900272

Received 11 June 2003/ Returned for modification 11 August 2003/ Accepted 26 September 2003

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.

* Corresponding author. Mailing address: Department of Pathology, Childrens Hospital Los Angeles, Keck School of Medicine, University of Southern California, 4650 Sunset Blvd., M.S. #103, Los Angeles, CA 90027. Phone: (323) 669-4625. Fax: (323) 671-1538. E-mail: jbadger{at}chla.usc.edu.

Editor: B. B. Finlay

Infection and Immunity, January 2004, p. 478-488, Vol. 72, No. 1
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.1.478-488.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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