The Journal of Experimental Medicine
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Published online 7 May 2001.
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© The Rockefeller University Press, 0022-1007/2001/5/1077/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 9, May 7, 2001 1077-1086


Original Article

Invasion and Persistent Intracellular Colonization of Erythrocytes: A Unique Parasitic Strategy of the Emerging Pathogen Bartonella



Ralf Schüleina,b, Anja Seuberta,b, Christian Gilleb, Christa Lanzb, Yves Hansmannc, Yves Piémontc, and Christoph Dehioa,b

a Biozentrum of the University of Basel, Department of Molecular Microbiology, CH-4056 Basel, Switzerland
b Max Planck Institute for Biology, Department of Infection Biology, D-72076 Tübingen, Germany
c Institute of Bacteriology, Faculty of Medicine, University Louis Pasteur, F-67000 Strasbourg, France
Biozentrum of the University of Basel, Dept. of Molecular Microbiology, Klingelbergstrasse 70, CH-4056 Basel, Switzerland.41-61-267-211841-61-267-2140

christoph.dehio{at}unibas.ch

The expanding genus Bartonella includes zoonotic and human-specific pathogens that can cause a wide range of clinical manifestations. A productive infection allowing bacterial transmission by blood-sucking arthropods is marked by an intraerythrocytic bacteremia that occurs exclusively in specific human or animal reservoir hosts. Incidental human infection by animal-adapted bartonellae can cause disease without evidence for erythrocyte parasitism. A better understanding of the intraerythrocytic lifestyle of bartonellae may permit the design of strategies to control the reservoir and transmittable stages of these emerging pathogens. We have dissected the process of Bartonella erythrocyte parasitism in experimentally infected animals using a novel approach for tracking blood infections based on flow cytometric quantification of green fluorescent protein–expressing bacteria during their interaction with in vivo–biotinylated erythrocytes. Bacteremia onset occurs several days after inoculation by a synchronous wave of bacterial invasion into mature erythrocytes. Intracellular bacteria replicate until reaching a stagnant number, which is sustained for the remaining life span of the infected erythrocyte. The initial wave of erythrocyte infection is followed by reinfection waves occurring at intervals of several days. Our findings unravel a unique bacterial persistence strategy adapted to a nonhemolytic intracellular colonization of erythrocytes that preserves the pathogen for efficient transmission by blood-sucking arthropods.

Key Words: Bartonella • erythrocyte parasitism • flow cytometry • GFP • whole blood biotinylation


Abbreviations used in this paper: Btr, Bartonella tribocorum; d.p.i., days post-inoculation; FL, fluorescence channel; GFP, green fluorescent protein; TEM, transmission electron microscopy.

R. Schülein and A. Seubert contributed equally to this work.

© 2001 The Rockefeller University Press


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