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Space flight alters bacterial gene expression and virulence and reveals a role for global regulator Hfq.

ABSTRACT: 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.

SUBMITTER: Wilson JW

PROVIDER: S-EPMC2042201 | biostudies-literature | 2007 Oct

REPOSITORIES: biostudies-literature

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Space flight alters bacterial gene expression and virulence and reveals a role for global regulator Hfq.

Wilson J W JW Ott C M CM Höner zu Bentrup K K Ramamurthy R R Quick L L Porwollik S S Cheng P P McClelland M M Tsaprailis G G Radabaugh T T Hunt A A Fernandez D D Richter E E Shah M M Kilcoyne M M Joshi L L Nelman-Gonzalez M M Hing S S Parra M M Dumars P P Norwood K K Bober R R Devich J J Ruggles A A Goulart C C Rupert M M Stodieck L L Stafford P P Catella L L Schurr M J MJ Buchanan K K Morici L L McCracken J J Allen P P Baker-Coleman C C Hammond T T Vogel J J Nelson R R Pierson D L DL Stefanyshyn-Piper H M HM Nickerson C A CA

Proceedings of the National Academy of Sciences of the United States of America 20070927 41

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 mi ...[more]

PMID: 17901201

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Project description:BackgroundYersinia pestis is the causative agent of plague, which is transmitted primarily between fleas and mammals and is spread to humans through the bite of an infected flea or contact with afflicted animals. Hfq is proposed to be a global post-transcriptional regulator that acts by mediating interactions between many regulatory small RNAs (sRNAs) and their mRNA targets. Sequence comparisons revealed that Y. pestis appears to produce a functional homologue of E. coli Hfq.Methodology and principal findingsPhenotype comparisons using in vitro assays demonstrated that Y. pestis Hfq was involved in resistance to H(2)O(2), heat and polymyxin B and contributed to growth under nutrient-limiting conditions. The role of Hfq in Y. pestis virulence was also assessed using macrophage and mouse infection models, and the gene expression affected by Hfq was determined using microarray-based transcriptome and real time PCR analysis. The macrophage infection assay showed that the Y. pestis hfq deletion strain did not have any significant difference in its ability to associate with J774A.1 macrophage cells. However, hfq deletion appeared to significantly impair the ability of Y. pestis to resist phagocytosis and survive within macrophages at the initial stage of infection. Furthermore, the hfq deletion strain was highly attenuated in mice after subcutaneous or intravenous injection. Transcriptome analysis supported the results concerning the attenuated phenotype of the hfq mutant and showed that the deletion of the hfq gene resulted in significant alterations in mRNA abundance of 243 genes in more than 13 functional classes, about 23% of which are known or hypothesized to be involved in stress resistance and virulence.Conclusions and significanceOur results indicate that Hfq is a key regulator involved in Y. pestis stress resistance, intracellular survival and pathogenesis. It appears that Hfq acts by controlling the expression of many virulence- and stress-associated genes, probably in conjunction with small noncoding RNAs.

Dataset Information

Space flight alters bacterial gene expression and virulence and reveals a role for global regulator Hfq.

Publications

Space flight alters bacterial gene expression and virulence and reveals a role for global regulator Hfq.

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