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Infection and Immunity, November 1999, p. 6168-6172, Vol. 67, No. 11
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Effect of mutS and recD Mutations on Salmonella Virulence

Thomas C. Zahrt,1,dagger Nancy Buchmeier,2 and Stanley Maloy1,*

Department of Microbiology, University of Illinois, Urbana, Illinois 61801,1 and Department of Pathology, University of California---San Diego, La Jolla, California 920932

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.


* 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.

dagger Present address: Department of Microbiology and Immunology, University of Michigan Medical Center, Ann Arbor, MI 48109.


Infection and Immunity, November 1999, p. 6168-6172, Vol. 67, No. 11
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.



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