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Infection and Immunity, January 2004, p. 489-497, Vol. 72, No. 1
0019-9567/04/$08.00+0 DOI: 10.1128/IAI.72.1.489-497.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
Listeriosis in the Pregnant Guinea Pig: a Model of Vertical Transmission
Anna I. Bakardjiev,1* Brian A. Stacy,2 Susan J. Fisher,3,4,5 and Daniel A. Portnoy1,6
Department of Molecular and Cell Biology,1
School of Public Health, University of California, Berkeley,6
Anatomic Pathology Service, Veterinary Medical Teaching Hospital, University of California, Davis,2
Departments of Stomatology,3
Anatomy,4
Pharmaceutical Chemistry, University of California, San Francisco, California5
Received 16 June 2003/
Returned for modification 18 August 2003/
Accepted 17 September 2003
Feto-placental infections represent a major cause of pregnancy complications, and yet the underlying molecular and cellular mechanisms of vertical transmission are poorly understood. Listeria monocytogenes, a facultative intracellular pathogen, is one of a group of pathogens that are known to cause feto-placental infections in humans and other mammals. The purpose of this study was to evaluate possible mechanisms of vertical transmission of L. monocytogenes. Humans and guinea pigs have a hemochorial placenta, where a single layer of fetally derived trophoblasts separates maternal from fetal circulation. We characterized L. monocytogenes infection of the feto-placental unit in a pregnant guinea pig model and in primary human trophoblasts and trophoblast-derived cell lines. The clinical manifestations of listeriosis in the pregnant guinea pigs and the tropism of L. monocytogenes to the guinea pig placenta resembled those in humans. Trophoblast cell culture systems were permissive for listerial growth and cell-to-cell spread and revealed that L. monocytogenes deficient in internalin A, a virulence factor that mediates invasion of nonphagocytic cells, was 100-fold defective in invasion. However, crossing of the feto-placental barrier in the guinea pig model was independent of internalin A, suggesting a negligible role for internalin-mediated direct invasion of trophoblasts in vivo. Further understanding of vertical transmission of L. monocytogenes will help in designing more effective means of treatment and disease prevention.
* Corresponding author. Mailing address: Department of Molecular and Cell Biology, Portnoy Lab, 510 Barker Hall, University of California, Berkeley, CA 94720-3202. Phone: (510) 643-3926. Fax: (510) 643-6334. E-mail:
annaib{at}uclink.berkeley.edu.
Editor: V. J. DiRita
Infection and Immunity, January 2004, p. 489-497, Vol. 72, No. 1
0019-9567/04/$08.00+0 DOI: 10.1128/IAI.72.1.489-497.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
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