coordinated regulation of virulence during systemic infection of salmonella enterica serovar typhimurium协调监管的毒性在全身感染的鼠伤寒沙门氏菌血清型.pdf

Coordinated Regulation of Virulence during Systemic Infection of Salmonella enterica Serovar Typhimurium 1 2 3 3 1 Hyunjin Yoon , Jason E. McDermott , Steffen Porwollik , Michael McClelland , Fred Heffron * 1 Department of Molecular Microbiology and Immunology, Oregon Health Science University, Portland, Oregon, United States of America, 2 Pacific Northwest National Laboratories, Richland, Washington, United States of America, 3 The Sydney Kimmel Cancer Center, San Diego, California, United States of America Abstract To cause a systemic infection, Salmonella must respond to many environmental cues during mouse infection and express specific subsets of genes in a temporal and spatial manner, but the regulatory pathways are poorly established. To unravel how micro-environmental signals are processed and integrated into coordinated action, we constructed in-frame non-polar deletions of 83 regulators inferred to play a role in Salmonella enteriditis Typhimurium (STM) virulence and tested them in three virulence assays (intraperitoneal [i.p.], and intragastric [i.g.] infection in BALB/c mice, and persistence in 129X1/SvJ mice). Overall, 35 regulators were identified whose absence attenuated virulence in at least one assay, and of those, 14 regulators were required for systemic mouse infection, the most stringent virulence assay. As a first step towards understanding the interplay between a pathogen and its host from a systems biology standpoint, we focused on these 14 genes. Transcriptional profiles were obtained for deletions of each of these 14 regulators grown under four different environmental conditions. These results, as well as publicly available transcriptional profiles, were analyzed using bo