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Infection and Immunity, July 2000, p. 4102-4107, Vol. 68, No. 7
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Identification of Genes Required for Chronic
Persistence of Brucella abortus in Mice
Priscilla C.
Hong,
Renée M.
Tsolis,* and
Thomas A.
Ficht
Department of Veterinary Pathobiology,
College of Veterinary Medicine, Texas A&M University, College
Station, Texas 77843-4467
Received 8 December 1999/Returned for modification 1 February
2000/Accepted 19 April 2000
The genetic basis for chronic persistence of Brucella
abortus in lymphoid organs of mice, cows, and humans is currently
unknown. We identified B. abortus genes involved in chronic
infection, by assessing the ability of 178 signature-tagged mutants to
establish and maintain persistent infection in mice. Each mutant was
screened for its ability to colonize the spleens of mice at 2 and 8 weeks after inoculation. Comparison of the results from both time
points identified two groups of mutants attenuated for chronic
infection in mice. The first group was not recovered at either 2 or 8 weeks postinfection and was therefore defective in establishing
infection. Mutants in this group carried transposon insertions in genes
involved in lipopolysaccharide biosynthesis (wbkA), in
aromatic amino acid biosynthesis, and in type IV secretion
(virB1 and virB10). The second group, which was
recovered at wild-type levels 2 weeks postinfection but not 8 weeks
postinfection was able to establish infection but was unable to
maintain chronic infection. One mutant in this group carried a
transposon insertion in a gene with homology to gcvB of
Mycobacterium tuberculosis, encoding glycine dehydrogenase, an enzyme whose activity is increased during the state of
nonreplicating persistence. These results suggest that some mechanisms
for long-term persistence may be shared among chronic intracellular
pathogens. Furthermore, identification of two groups of genes, those
required for initiating infection and those required only for long-term persistence, suggests that B. abortus uses distinct sets of
virulence determinants to establish and maintain chronic infection in mice.
*
Corresponding author. Mailing address: Department of
Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M
University, College Station, TX 77843-4467. Phone: (979) 862-4779. Fax:
(979) 862-1088. E-mail: rtsolis{at}cvm.tamu.edu.
Infection and Immunity, July 2000, p. 4102-4107, Vol. 68, No. 7
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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