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Infection and Immunity, July 2005, p. 4354-4362, Vol. 73, No. 7
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.7.4354-4362.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

SlyA Regulates Function of Salmonella Pathogenicity Island 2 (SPI-2) and Expression of SPI-2-Associated Genes

Department of Infectious Diseases, Centre for Molecular Microbiology and Infection, Imperial College London, The Flowers Building, Armstrong Road, London SW7 2AZ, United Kingdom

Received 18 August 2004/ Returned for modification 5 November 2004/ Accepted 1 April 2005

During the systemic phase of murine infection with Salmonella enterica serovar Typhimurium, bacterial virulence is correlated with the ability to grow and survive within host macrophages. Salmonella pathogenicity island 2 (SPI-2), encoding a type three secretion system, has emerged as an important contributor to Salmonella intracellular growth. SPI-2 mutants have been proposed to be more accessible than wild-type Salmonella to oxyradicals generated by the NADPH phagocyte oxidase. We performed mixed infections of mice to investigate the relationship between SPI-2 and SlyA, a transcriptional regulator that confers resistance to oxyradicals. In mixed-infection experiments, the SPI-2 null mutant was severely attenuated in virulence, whereas slyA mutants were only mildly attenuated. Surprisingly, further experiments indicated that the function of SPI-2 was partially dependent on slyA. The intracellular behavior of a slyA mutant in infected cells was consistent with inefficient SPI-2 expression, as formation of Salmonella-induced filaments and the intracellular F-actin meshwork, features that depend on SPI-2, were present at abnormally low frequencies. Furthermore, the translocated levels of the SPI-2 effector SseJ were severely reduced in a strain carrying a mutation in slyA. We used flow cytometry to investigate the role of SlyA in expression of green fluorescent protein (GFP) from transcriptional fusions with promoters of either of two other SPI-2 effector genes, sifB and sifA. The slyA mutant exhibited reduced GFP expression from both promoters. Combining mutations in slyA and other regulators of SPI-2 indicated that SlyA acts through the SsrAB two-component regulatory system. SlyA exhibits partial functional redundancy with OmpR-EnvZ and contributes to the transcriptional response to low osmolarity and the absence of calcium, two environmental stimuli that promote SPI-2 gene expression.

Editor: V. J. DiRita

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