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Infection and Immunity, August 2003, p. 4229-4237, Vol. 71, No. 8
0019-9567/03/$08.00+0 DOI: 10.1128/IAI.71.8.4229-4237.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
Survival, Replication, and Antibody Susceptibility of Ehrlichia chaffeensis outside of Host Cells
Julia Shu-yi Li1,2 and Gary M. Winslow1*
Wadsworth Center, New York State Department of Health, Albany, New York 12201-2002,1
Department of Biomedical Sciences, School of Public Health, University at Albany, Albany, New York 12201-05092
Received 12 December 2002/
Returned for modification 28 January 2003/
Accepted 9 April 2003
Ehrlichia chaffeensis, an obligate intracellular, tick-transmitted bacterium, is susceptible to antibody-mediated host defense, but the mechanism by which this occurs is not understood. One possible explanation is that antibodies directly access the bacteria in the extracellular environment of the host, perhaps during bacterial intercellular transfer. Accordingly, we investigated whether bacteria could be found outside of host cells during infection. Host cell-free plasma obtained from infected mice was found to contain ehrlichiae, and the host cell-free ehrlichiae readily transferred disease to susceptible SCID recipients. The host cell-free ehrlichiae were found during infection of both immunocompetent BALB/c and immunocompromised BALB/c-scid mice and reached levels as high as 108/ml in plasma during persistent infection in SCID mice. Approximately 10% of the blood-borne bacteria were found outside of host cells. Although it is generally accepted that replication of ehrlichiae occurs only within host cells, the cell-free bacteria were shown to undergo DNA replication and cell division in vitro for 3 to 5 days when incubated at 37°C in plasma. Paradoxically, both infectivity and virulence were lost after 24 h of ex vivo culture. The data indicate that E. chaffeensis is exposed to the extracellular milieu during infection, presumably during intercellular transfer, and reveal that these intracellular bacteria do not require the environment of the host cell for replication. Our findings reveal a possible mechanism by which antibodies can access the intracellular bacteria upon their release into the extracellular milieu and mediate host defense and also have implications for understanding the replication and transmission of this vector-borne pathogen.
* Corresponding author. Mailing address: Wadsworth Center, 120 New Scotland Avenue, Albany, NY 12208. Phone: (518) 473-2795. Fax: (518) 486-4395. E-mail: gary.winslow{at}wadsworth.org.
Editor: T. R. Kozel
Infection and Immunity, August 2003, p. 4229-4237, Vol. 71, No. 8
0019-9567/03/$08.00+0 DOI: 10.1128/IAI.71.8.4229-4237.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
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Copyright © 2003 by the American Society for Microbiology. All rights reserved.