Previous Article | Next Article ![]()
Infection and Immunity, July 1999, p. 3548-3557, Vol. 67, No. 7
Department of Pathobiology, University of
Guelph, Guelph, Ontario N1G 2W1, Canada1;
Howard Hughes Medical Research Institute, Albert Einstein
College of Medicine, Bronx, New York 104612;
and Department of Microbiology and Immunology, Temple
University School of Medicine, Philadelphia, Pennsylvania
191403
Received 28 January 1999/Returned for modification 25 February
1999/Accepted 5 April 1999
Rhodococcus equi is a facultative intracellular
pathogen of macrophages and a cause of pneumonia in young horses
(foals) and immunocompromised people. Isolates of R. equi from pneumonic foals typically contain large, 85- or 90-kb
plasmids encoding a highly immunogenic virulence-associated protein
(VapA). The objective of this study was to determine the role of the
85-kb plasmid and VapA in the intracellular survival and
virulence of R. equi. Clinical isolates
containing the plasmid and expressing VapA efficiently replicated
within mouse macrophages in vitro, while plasmid-cured derivatives of these organisms did not multiply intracellularly. An
isolate harboring the large plasmid also replicated in the tissues of
experimentally infected mice, whereas its plasmid-cured derivative was
rapidly cleared. All foals experimentally infected with a
plasmid-containing clinical isolate developed severe
bronchopneumonia, whereas the foals infected with its plasmid-cured
derivative remained asymptomatic and free of visible lung lesions. By
day 14 postinfection, lung bacterial burdens had increased considerably
in foals challenged with the plasmid-containing clinical isolate. In
contrast, bacteria could no longer be cultured from the lungs of foals
challenged with the isogenic plasmid-cured derivative. A recombinant,
plasmid-cured derivative expressing wild-type levels of VapA failed to
replicate in macrophages and remained avirulent for both mice and
foals. These results show that the 85-kb plasmid of R. equi is essential for intracellular replication within
macrophages and for development of disease in the native host, the
foal. However, expression of VapA alone is not sufficient to restore
the virulence phenotype.
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Role of the 85-Kilobase Plasmid and Plasmid-Encoded
Virulence-Associated Protein A in Intracellular Survival and
Virulence of Rhodococcus equi
*
Corresponding author. Mailing address: Department of
Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario N1G 2W1, Canada. Phone: (519) 824-4120, ext. 4716. Fax: (519)
767-0809. E-mail: jprescott{at}ovcnet.uoguelph.ca.
This article has been cited by other articles:
| J. Bacteriol. | J. Virol. | Eukaryot. Cell |
|---|
| Microbiol. Mol. Biol. Rev. | Clin. Vaccine Immunol. | All ASM Journals |
|---|