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Infection and Immunity, November 1999, p. 6168-6172, Vol. 67, No. 11
Department of Microbiology, University of
Illinois, Urbana, Illinois 61801,1 and
Department of Pathology, University of California
Received 5 February 1999/Returned for modification 17 March
1999/Accepted 23 August 1999
Hybrid derivatives of closely related bacteria may be used to
dissect strain-specific functions that contribute to virulence within a
host. However, mismatches between DNA sequences are a potent barrier to
recombination. Recipients with mutS and recD mutations overcome this barrier, allowing construction of genetic hybrids. To determine whether Salmonella hybrids
constructed in a mutS recD host can be used to study
virulence, we assayed the effect of mutS and
recD mutations on the virulence of Salmonella typhimurium 14028s in mice. Mutants defective in either
mutS or recD do not affect the time course or
the 50% lethal dose (LD50) of the infection. In contrast,
the inactivation of both mutS and recD results
in a synthetic phenotype which substantially increases the time
required to cause a lethal infection without changing the
LD50. This phenotype results from an inability of
mutS recD double mutants to rapidly adapt to
purine-limiting conditions present within macrophages. Although the
disease progression is slower, S. typhimurium mutS recD
mutants retain the ability to cause lethal infections, and, thus,
hybrids constructed in mutS recD hosts may permit the
analysis of virulence factors in a surrogate animal model.
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Effect of mutS and recD
Mutations on Salmonella Virulence

San
Diego, La Jolla, California 920932
*
Corresponding author. Mailing address: Department of
Microbiology, University of Illinois, B103 CLSL, 601 S. Goodwin
Ave., Urbana, IL 61801. Phone: (217) 333-3122. Fax: (217)
244-6697. E-mail: s-maloy{at}life.uiuc.edu.
Present address: Department of Microbiology and Immunology,
University of Michigan Medical Center, Ann Arbor, MI 48109.
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