Hindawi Publishing Corporation Comparative and Functional Genomics Volume 2010, Article ID 342168, 11 pages doi:10.1155/2010/342168 Research Article Comparative Global Gene Expression Profiles of Wild-Type Yersinia pestis CO92 and Its Braun Lipoprotein Mutant at Flea and Human Body Temperatures Cristi L. Galindo, 1, 2 Jian Sha, 1 Scott T. Moen, 1 Stacy L. Agar, 1 Michelle L. Kirtley, 1 Sheri M. Foltz, 1 Lauren J. McIver, 2 E. V. Kozlova, 1 Harold R. Garner, 2 and Ashok K. Chopra 1 1 Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, TX 77555-1070, USA 2 Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA 02461-0477, USA Correspondence should be addressed to Ashok K. Chopra, achopra@utmb.edu Received 20 January 2010; Accepted 22 February 2010 Academic Editor: Antoine Danchin Copyright © 2010 Cristi L. Galindo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Braun/murein lipoprotein (Lpp) is involved in inflammatory responses and septic shock. We previously characterized a Δlpp mutant of Yersinia pestis CO92 and found that this mutant was defective in surviving in macrophages and was attenuated in a mouse inhalation model of plague when compared to the highly virulent wild-type (WT) bacterium. We performed global transcriptional profiling of WT Y. pestis and its Δlpp mutant using microarrays. The organisms were cultured at 26 and 37 degrees Celsius to simulate the flea vector and mammalian host environments, respectively. Our data revealed vastly different effects of lpp mutation on the transcriptomes of Y. pestis grown at 37 versus 26 ◦ C. While the absence of Lpp resulted mainly in the downregulation of metabolic genes at 26 ◦ C, the Y. pestis Δlpp mutant cultured at 37 ◦ C exhibited profound alterations in stress response and virulence genes, compared to WT bacteria. We investigated one of the stress-related genes (htrA) downregulated in the Δlpp mutant relative to WT Y. pestis. Indeed, complementation of the Δlpp mutant with the htrA gene restored intracellular survival of the Y. pestis Δlpp mutant. Our results support a role for Lpp in Y. pestis adaptation to the host environment, possibly via transcriptional activation of htrA. 1. Introduction Yersinia pestis is the causative agent of plague, and its current relevance as a potential bioweapon is garnered because of its high virulence and the development of multiantibiotic resistant strains by several governments prior to the 1972 Biological and Toxic Weapons Convention ban [1]. This gram-negative bacterium is naturally transmitted via a flea vector and prefers rodents as a reservoir. Plague can manifest itself in three different stages of disease progression: bubonic, septicemic, and pneumonic forms. Bubonic plague is the classic form where a flea vector bite leads to fever, headache, and the prototypical “buboes” or swollen lymph nodes in humans. Septicemic plague may result from a flea bite or inspiration; however, the disease progression leads quickly to high mortality with emesis, hemorrhagic rash, and high fever as its signs. Finally, pneumonic plague is spread person- to-person and is marked by fever, coughs, dyspnea, and hemoptysis. The aerosol is short-lived, as sunlight and desiccation destroy the bacterium. However, the dogma that Y. pestis is not hardy in the environment has been questioned as of late because it has been shown to remain viable on some fomites for over 72 hours [2] and can remain viable in the soil for approximately 40 weeks [3]. Even more notable than bacterial persistence is its virulence. A variety of virulence factor-encoding genes are found both on the chromosome and in plasmids. The pPCP1 plasmid contains the plasminogen-activating protease (Pla) which has been shown to interfere with the complement activation cascade and blood coagulation as well as decrease the extracellular matrix around the foci facilitating bacterial dissemination to peripheral organs [4]. Surface-bound Pla