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Media ion composition controls regulatory and virulence response of Salmonella in spaceflight.

ABSTRACT: The spaceflight environment is relevant to conditions encountered by pathogens during the course of infection and induces novel changes in microbial pathogenesis not observed using conventional methods. It is unclear how microbial cells sense spaceflight-associated changes to their growth environment and orchestrate corresponding changes in molecular and physiological phenotypes relevant to the infection process. Here we report that spaceflight-induced increases in Salmonella virulence are regulated by media ion composition, and that phosphate ion is sufficient to alter related pathogenesis responses in a spaceflight analogue model. Using whole genome microarray and proteomic analyses from two independent Space Shuttle missions, we identified evolutionarily conserved molecular pathways in Salmonella that respond to spaceflight under all media compositions tested. Identification of conserved regulatory paradigms opens new avenues to control microbial responses during the infection process and holds promise to provide an improved understanding of human health and disease on Earth.

SUBMITTER: Wilson JW

PROVIDER: S-EPMC2592540 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

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Media ion composition controls regulatory and virulence response of Salmonella in spaceflight.

Wilson James W JW Ott C Mark CM Quick Laura L Davis Richard R Höner zu Bentrup Kerstin K Crabbé Aurélie A Richter Emily E Sarker Shameema S Barrila Jennifer J Porwollik Steffen S Cheng Pui P McClelland Michael M Tsaprailis George G Radabaugh Timothy T Hunt Andrea A Shah Miti M Nelman-Gonzalez Mayra M Hing Steve S Parra Macarena M Dumars Paula P Norwood Kelly K Bober Ramona R Devich Jennifer J Ruggles Ashleigh A CdeBaca Autumn A Narayan Satro S Benjamin Joseph J Goulart Carla C Rupert Mark M Catella Luke L Schurr Michael J MJ Buchanan Kent K Morici Lisa L McCracken James J Porter Marc D MD Pierson Duane L DL Smith Scott M SM Mergeay Max M Leys Natalie N Stefanyshyn-Piper Heidemarie M HM Gorie Dominic D Nickerson Cheryl A CA

PloS one 20081212 12

The spaceflight environment is relevant to conditions encountered by pathogens during the course of infection and induces novel changes in microbial pathogenesis not observed using conventional methods. It is unclear how microbial cells sense spaceflight-associated changes to their growth environment and orchestrate corresponding changes in molecular and physiological phenotypes relevant to the infection process. Here we report that spaceflight-induced increases in Salmonella virulence are regul ...[more]

PMID: 19079590

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Project description:We have shown that the ligand-responsive MarR family member SlyA plays an important role in transcription activation of multiple virulence genes in Salmonella enterica serovar Typhimurium by responding to guanosine tetraphosphate (ppGpp). Here, we demonstrate that another MarR family member, EmrR, is required for virulence of S. Typhimurium and another enteric bacterium, Yersinia pestis EmrR is found to activate transcription of an array of virulence determinants, including Salmonella pathogenicity island 2 (SPI-2) genes and several divergent operons, which have been shown to be activated by SlyA and the PhoP/PhoQ two-component system. We studied the regulatory effect of EmrR on one of these genetic loci, i.e., the pagC-pagD divergent operon, and characterized a catecholamine neurotransmitter, dopamine, as an EmrR-sensed signal. Dopamine acts on EmrR to reduce its ability to bind to the target promoters, thus functioning as a negative signal to downregulate this EmrR-activated transcription. EmrR can bind to AT-rich sequences, which particularly overlap the SlyA and PhoP binding sites in the pagC-pagD divergent promoter. EmrR is a priming transcription regulator that binds its target promoters prior to successive transcription activators, by which it displaces universal silencer H-NS from these promoters and facilitates successive regulators to bind these regions. Regulation of the Salmonella-specific gene in Escherichia coli and Y. pestis reveals that EmrR-dependent regulation is conserved in enteric bacteria. These observations suggest that EmrR is a transcription activator to control the expression of virulence genes, including the SPI-2 genes. Dopamine can act on the EmrR-mediated signal transduction, thus downregulating expression of these virulence factors.IMPORTANCE In this study, MarR family regulator EmrR is identified as a novel virulence factor of enteric bacteria, here exemplified by Salmonella enterica serovar Typhimurium and Yersinia pestis EmrR exerts an essential effect as a transcription activator for expression of virulence determinants, including Salmonella pathogenicity island 2 genes and a set of horizontally acquired genetic loci that formed divergent operons. EmrR senses the neurotransmitter dopamine and is subsequently released from target promoters, resulting in downregulation of the virulence gene expression. Through this action on EmrR, dopamine can weaken Salmonella resistance against host defense mechanisms. This provides an explanation for the previous observation that dopamine inhibits bacterial infection in animal gastrointestinal tracts. Our findings provide evidence that this neurotransmitter can modulate bacterial gene expression through interaction with virulence regulator EmrR.

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Media ion composition controls regulatory and virulence response of Salmonella in spaceflight.

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Media ion composition controls regulatory and virulence response of Salmonella in spaceflight.

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