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Infection and Immunity, July 2005, p. 4338-4345, Vol. 73, No. 7
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.7.4338-4345.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

sciS, an icmF Homolog in Salmonella enterica Serovar Typhimurium, Limits Intracellular Replication and Decreases Virulence

Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon 97201

Received 21 December 2004/ Returned for modification 1 February 2005/ Accepted 10 March 2005

Salmonella enterica serovar Typhimurium utilizes macrophages to disseminate from the intestine to deeper tissues within the body. While S. enterica serovar Typhimurium has been shown to kill its host macrophage, it can persist intracellularly beyond 18 h postinfection. To identify factors involved in late stages of infection, we screened a transposon library made in S. enterica serovar Typhimurium for the ability to persist in J774 macrophages at 24 h postinfection. Through this screen, we identified a gene, sciS, found to be homologous to icmF in Legionella pneumophila. icmF, which is required for intracellular multiplication, is conserved in several gram-negative pathogens, and its homolog appears to have been acquired horizontally in S. enterica serovar Typhimurium. We found that an sciS mutant displayed increased intracellular numbers in J774 macrophages when compared to the wild-type strain at 24 h postinfection. sciS was maximally transcribed at 27 h postinfection and is repressed by SsrB, an activator of genes required for promoting intracellular survival. Finally, we demonstrate that an sciS mutant is hypervirulent in mice when administered intragastrically. Taken together, these data indicate a role for SciS in controlling intracellular bacterial levels at later stages of infection and attenuating virulence in a murine host

Editor: F. C. Fang

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