TraJ-DependentEscherichia coliK1 Interactions with Professional Phagocytes Are Important for Early Systemic Dissemination of Infection in the Neonatal Rat

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Abstract
Escherichia coliis a major cause of neonatal bacterial sepsis and meningitis. We recently identified a gene,traJ, which contributes to the ability ofE. coliK1 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 atraJmutant to cause systemic disease in the neonatal rat. Our studies determined that thetraJmutant 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 thetraJmutant 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 ofE. coliK1 and that TraJ significantly contributes to the predominantly intracellular nature ofE. coliK1 within these professional phagocytes exclusively during the early stages of systemic disease. These data indicate that, contrary to earlier indications,E. coliK1 resides within professional phagocytes, and this is essential for the efficient progression of systemic disease.