B-174. Integrated Regulation of Virulence Factors during Systemic Infection of Salmonella enterica Serovar Typhimurium

H. Yoon1, S. Porwollik2, M. McClelland2, J. McDermott3, F. Heffron1;
1Oregon Hlth. & Sci. Univ., Portland, OR, 2Sidney Kimmel Cancer Ctr., San Diego, CA, 3Pacific Northwest Natl. Lab., Richland, WA.

To respond to profoundly different microenvironments within its host, Salmonella must appropriately regulate distinct arrays of virulence factors. As a first step in understanding how virulence is regulated, we constructed in-frame non-polar deletions of 84 regulators thought to play a role in Salmonella typhimurium virulence and tested them for virulence in three different assays. Transcription profiling was carried for each of the 15 most attenuated mutants under four different growth conditions. All 15 regulators coordinately activate transcription of many genes including many in Salmonella pathogenicity island 1 and 2 under one or more growth conditions. Transcription of many SPI-2 genes was decreased simultaneously in 15 mutant derivatives in acidic MgM minimal media; conditions that mimic the intracellular environment. Computer analysis of the transcription profiles suggests a particular hierarchy of regulation and provides insight into how Salmonella may coordinate regulation within its host.