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Published online on September 27, 2007, 10.1073/pnas.0707155104
PNAS | October 9, 2007 | vol. 104 | no. 41 | 16299-16304


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BIOLOGICAL SCIENCES / MICROBIOLOGY
Space flight alters bacterial gene expression and virulence and reveals a role for global regulator Hfq

J. W. Wilsona,b, C. M. Ottc, K. Höner zu Bentrupb, R. Ramamurthyb, L. Quicka, S. Porwollikd, P. Chengd, M. McClellandd, G. Tsaprailise, T. Radabaughe, A. Hunte, D. Fernandeza, E. Richtera, M. Shahf, M. Kilcoynef, L. Joshif, M. Nelman-Gonzalezg, S. Hingh, M. Parrah, P. Dumarsh, K. Norwoodi, R. Boberi, J. Devichi, A. Rugglesi, C. Goulartj, M. Rupertj, L. Stodieckj, P. Staffordk, L. Catellai, M. J. Schurrb,l, K. Buchananb,m, L. Moricib, J. McCrackenb,n, P. Allenb,o, C. Baker-Colemanb,o, T. Hammondb,o, J. Vogelp, R. Nelsonq, D. L. Piersonc, H. M. Stefanyshyn-Piperr, and C. A. Nickersona,b,s

aCenter for Infectious Diseases and Vaccinology, fCenter for Glycoscience Technology, kCenter for Innovations in Medicine, and qCenter for Combinatorial Sciences, The Biodesign Institute, Arizona State University, Tempe, AZ 85287; bTulane University Health Sciences Center, New Orleans, LA 70112; cHabitability and Environmental Factors Division and rAstronaut Office, Johnson Space Center, National Aeronautics and Space Administration, Houston, TX 77058; dSidney Kimmel Cancer Center, San Diego, CA 92121; eCenter for Toxicology, University of Arizona, Tucson, AZ 85721; gWyle Laboratories, Houston, TX 77058; hAmes Research Center, National Aeronautics and Space Administration, Moffett Field, CA 94035; iSpace Life Sciences Laboratory, Kennedy Space Center, Cape Canaveral, FL 32920; jBioServe, University of Colorado, Boulder, CO 80309; lUniversity of Colorado at Denver and Health Sciences Center, Denver, CO 80262; mOklahoma City University, Oklahoma City, OK 73106; nSection of General Surgery, University of Chicago, Chicago, IL 60637; oSoutheast Louisiana Veterans Health Care System, New Orleans, LA 70112; and pRNA Biology Group, Max Planck Institute for Infection Biology, 10117 Berlin, Germany

Edited by Arnold L. Demain, Drew University, Madison, NJ, and approved August 27, 2007 (received for review July 30, 2007)

A comprehensive analysis of both the molecular genetic and phenotypic responses of any organism to the space flight environment has never been accomplished because of significant technological and logistical hurdles. Moreover, the effects of space flight on microbial pathogenicity and associated infectious disease risks have not been studied. The bacterial pathogen Salmonella typhimurium was grown aboard Space Shuttle mission STS-115 and compared with identical ground control cultures. Global microarray and proteomic analyses revealed that 167 transcripts and 73 proteins changed expression with the conserved RNA-binding protein Hfq identified as a likely global regulator involved in the response to this environment. Hfq involvement was confirmed with a ground-based microgravity culture model. Space flight samples exhibited enhanced virulence in a murine infection model and extracellular matrix accumulation consistent with a biofilm. Strategies to target Hfq and related regulators could potentially decrease infectious disease risks during space flight missions and provide novel therapeutic options on Earth.

microgravity | Space Shuttle | low shear modeled microgravity | rotating wall vessel | Salmonella


Author contributions: J.W.W., C.M.O., K.H.z.B., R.R., L.Q., S.P., P.C., M.M., G.T., T.R., A.H., D.F., E.R., M.S., M.K., L.J., M.N.-G., S.H., M.P., P.D., K.N., R.B., J.D., A.R., C.G., M.R., L.S., L.C., M.J.S., K.B., L.M., J.M., P.A., C.B.-C., T.H., and C.A.N. designed research; J.W.W., C.M.O., K.H.z.B., R.R., L.Q., S.P., P.C., M.M., G.T., T.R., A.H., D.F., E.R., M.S., M.K., M.N.-G., S.H., M.P., P.D., C.G., M.R., M.J.S., K.B., L.M., J.M., P.A., C.B.-C., T.H., H.M.S.-P., and C.A.N. performed research; S.P., P.C., M.M., G.T., T.R., A.H., L.J., M.N.-G., L.S., P.S., J.V., R.N., and D.L.P. contributed new reagents/analytic tools; J.W.W., C.M.O., K.H.z.B., R.R., L.Q., S.P., P.C., M.M., G.T., T.R., A.H., D.F., E.R., M.S., M.K., L.J., M.N.-G., P.S., M.J.S., K.B., L.M., P.A., C.B.-C., T.H., and C.A.N. analyzed data; and J.W.W., C.M.O., and C.A.N. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

Data deposition: The data reported in this paper have been deposited in the Gene Expression Omnibus (GEO) database, www.ncbi.nlm.nih.gov/geo (accession no. GSE8573).

This article contains supporting information online at www.pnas.org/cgi/content/full/0707155104/DC1.

sTo whom correspondence should be addressed at: The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, 1001 South McAllister Avenue, Tempe, AZ 85287. E-mail: cheryl.nickerson{at}asu.edu

© 2007 by The National Academy of Sciences of the USA


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