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Infection and Immunity, December 1998, p. 5692-5697, Vol. 66, No. 12
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Environmental Growth Conditions Influence the Ability of Escherichia coli K1 To Invade Brain Microvascular Endothelial Cells and Confer Serum Resistance

Julie L. Badger,1 and Kwang Sik Kim1,2,*

Division of Infectious Diseases, Childrens Hospital Los Angeles,1 and University of Southern California School of Medicine,2 Los Angeles, California 90027

Received 6 August 1998/Returned for modification 2 September 1998/Accepted 17 September 1998

A major limitation to advances in prevention and therapy of neonatal meningitis is our incomplete understanding of the pathogenesis of this disease. In an effort to understand the pathogenesis of meningitis due to Escherichia coli K1, we examined whether environmental growth conditions similar to those that the bacteria might be exposed to in the blood could influence the ability of E. coli K1 to invade brain microvascular endothelial cells (BMEC) in vitro and to cross the blood-brain barrier in vivo. We found that the following bacterial growth conditions enhanced E. coli K1 invasion of BMEC 3- to 10-fold: microaerophilic growth, media buffered at pH 6.5, and media supplemented with 50% newborn bovine serum (NBS), magnesium, or iron. Growth conditions that significantly repressed invasion (i.e., 2- to 250-fold) included iron chelation, a pH of 8.5, and high osmolarity. More importantly, E. coli K1 traversal of the blood-brain barrier was significantly greater for the growth condition enhancing BMEC invasion (50% NBS) than for the condition repressing invasion (osmolarity) in newborn rats with experimental hematogenous meningitis. Of interest, bacterial growth conditions that enhanced or repressed invasion also elicited similar serum resistance phenotype patterns. This is the first demonstration that bacterial ability to enter the central nervous system can be affected by environmental growth conditions.

* Corresponding author. Mailing address: Division of Infectious Diseases, MS #51, Childrens Hospital Los Angeles, 4650 Sunset Blvd., Los Angeles, CA 90027. Phone: (213) 669-2509. Fax: (213) 660-2661. E-mail: KSKim%SMTPGATE{at}CHLAIS.usc.edu.

Infection and Immunity, December 1998, p. 5692-5697, Vol. 66, No. 12
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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