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Ethanolamine Signaling Promotes Salmonella Niche Recognition and Adaptation during Infection.

Anderson CJ, Clark DE, Adli M, Kendall MM - PLoS Pathog. (2015)

Bottom Line: Our findings reveal that S.Typhimurium co-opts ethanolamine as a signal to coordinate metabolism and then virulence.Because the ability to sense ethanolamine is a conserved trait among pathogenic and commensal bacteria, our work indicates that ethanolamine signaling may be a key step in the localized adaptation of bacteria within their mammalian hosts.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, Virginia, United States of America.

ABSTRACT
Chemical and nutrient signaling are fundamental for all cellular processes, including interactions between the mammalian host and the microbiota, which have a significant impact on health and disease. Ethanolamine is an essential component of cell membranes and has profound signaling activity within mammalian cells by modulating inflammatory responses and intestinal physiology. Here, we describe a virulence-regulating pathway in which the foodborne pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) exploits ethanolamine signaling to recognize and adapt to distinct niches within the host. The bacterial transcription factor EutR promotes ethanolamine metabolism in the intestine, which enables S. Typhimurium to establish infection. Subsequently, EutR directly activates expression of the Salmonella pathogenicity island 2 in the intramacrophage environment, and thus augments intramacrophage survival. Moreover, EutR is critical for robust dissemination during mammalian infection. Our findings reveal that S. Typhimurium co-opts ethanolamine as a signal to coordinate metabolism and then virulence. Because the ability to sense ethanolamine is a conserved trait among pathogenic and commensal bacteria, our work indicates that ethanolamine signaling may be a key step in the localized adaptation of bacteria within their mammalian hosts.

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Related in: MedlinePlus

EutR-associated signaling in vivo.(A) qRT-PCR analysis of ssrB expression in WT S. Typhimurium (SL1344) or the ΔeutR strain (CJA009) harvested from infected spleens. (B) qRT-PCR analysis of eutR or eutS expression in WT S. Typhimurium (SL1344) harvested from infected spleens compared to S. Typhimurium (SL1344) grown in tissue culture medium (DMEM). For (A) and (B), n = 2–3; error bars represent the geometric mean ± SD; strB was used as the endogenous control. *, P ≤ 0.05. nd = not detected.
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ppat.1005278.g007: EutR-associated signaling in vivo.(A) qRT-PCR analysis of ssrB expression in WT S. Typhimurium (SL1344) or the ΔeutR strain (CJA009) harvested from infected spleens. (B) qRT-PCR analysis of eutR or eutS expression in WT S. Typhimurium (SL1344) harvested from infected spleens compared to S. Typhimurium (SL1344) grown in tissue culture medium (DMEM). For (A) and (B), n = 2–3; error bars represent the geometric mean ± SD; strB was used as the endogenous control. *, P ≤ 0.05. nd = not detected.

Mentions: The in vitro studies identified targets of EutR-dependent gene regulation. To test our findings within the complexities of the in vivo environment, we assessed EutR-dependent regulation of ssrB using single strain infections and purified S. Typhimurium RNA from harvested spleens. Expression of ssrB was significantly decreased in the ΔeutR strain compared to WT (Fig 7A and S11 Fig), which is consistent with the data presented in Fig 4B. Additionally, we measured expression of eutR and eutS in WT S. Typhimurium recovered from the spleen relative to S. Typhimurium grown in vitro. Notably, eutR expression was significantly increased in the spleen, whereas expression of eutS was not detectable (Fig 7B). These data further highlight the dynamic role of EutR in S. Typhimurium pathogenesis from driving ethanolamine metabolism in the intestine to promoting virulence gene expression in later stages of disease.


Ethanolamine Signaling Promotes Salmonella Niche Recognition and Adaptation during Infection.

Anderson CJ, Clark DE, Adli M, Kendall MM - PLoS Pathog. (2015)

EutR-associated signaling in vivo.(A) qRT-PCR analysis of ssrB expression in WT S. Typhimurium (SL1344) or the ΔeutR strain (CJA009) harvested from infected spleens. (B) qRT-PCR analysis of eutR or eutS expression in WT S. Typhimurium (SL1344) harvested from infected spleens compared to S. Typhimurium (SL1344) grown in tissue culture medium (DMEM). For (A) and (B), n = 2–3; error bars represent the geometric mean ± SD; strB was used as the endogenous control. *, P ≤ 0.05. nd = not detected.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4643982&req=5

ppat.1005278.g007: EutR-associated signaling in vivo.(A) qRT-PCR analysis of ssrB expression in WT S. Typhimurium (SL1344) or the ΔeutR strain (CJA009) harvested from infected spleens. (B) qRT-PCR analysis of eutR or eutS expression in WT S. Typhimurium (SL1344) harvested from infected spleens compared to S. Typhimurium (SL1344) grown in tissue culture medium (DMEM). For (A) and (B), n = 2–3; error bars represent the geometric mean ± SD; strB was used as the endogenous control. *, P ≤ 0.05. nd = not detected.
Mentions: The in vitro studies identified targets of EutR-dependent gene regulation. To test our findings within the complexities of the in vivo environment, we assessed EutR-dependent regulation of ssrB using single strain infections and purified S. Typhimurium RNA from harvested spleens. Expression of ssrB was significantly decreased in the ΔeutR strain compared to WT (Fig 7A and S11 Fig), which is consistent with the data presented in Fig 4B. Additionally, we measured expression of eutR and eutS in WT S. Typhimurium recovered from the spleen relative to S. Typhimurium grown in vitro. Notably, eutR expression was significantly increased in the spleen, whereas expression of eutS was not detectable (Fig 7B). These data further highlight the dynamic role of EutR in S. Typhimurium pathogenesis from driving ethanolamine metabolism in the intestine to promoting virulence gene expression in later stages of disease.

Bottom Line: Our findings reveal that S.Typhimurium co-opts ethanolamine as a signal to coordinate metabolism and then virulence.Because the ability to sense ethanolamine is a conserved trait among pathogenic and commensal bacteria, our work indicates that ethanolamine signaling may be a key step in the localized adaptation of bacteria within their mammalian hosts.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, Virginia, United States of America.

ABSTRACT
Chemical and nutrient signaling are fundamental for all cellular processes, including interactions between the mammalian host and the microbiota, which have a significant impact on health and disease. Ethanolamine is an essential component of cell membranes and has profound signaling activity within mammalian cells by modulating inflammatory responses and intestinal physiology. Here, we describe a virulence-regulating pathway in which the foodborne pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) exploits ethanolamine signaling to recognize and adapt to distinct niches within the host. The bacterial transcription factor EutR promotes ethanolamine metabolism in the intestine, which enables S. Typhimurium to establish infection. Subsequently, EutR directly activates expression of the Salmonella pathogenicity island 2 in the intramacrophage environment, and thus augments intramacrophage survival. Moreover, EutR is critical for robust dissemination during mammalian infection. Our findings reveal that S. Typhimurium co-opts ethanolamine as a signal to coordinate metabolism and then virulence. Because the ability to sense ethanolamine is a conserved trait among pathogenic and commensal bacteria, our work indicates that ethanolamine signaling may be a key step in the localized adaptation of bacteria within their mammalian hosts.

Show MeSH
Related in: MedlinePlus