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Antivirulence activity of the human gut metabolome.

Antunes LC, McDonald JA, Schroeter K, Carlucci C, Ferreira RB, Wang M, Yurist-Doutsch S, Hira G, Jacobson K, Davies J, Allen-Vercoe E, Finlay BB - MBio (2014)

Bottom Line: Importance: Microbes can communicate through the production and sensing of small molecules.Within the complex ecosystem formed by commensal microbes living in and on the human body, it is likely that these molecular messages are used extensively during the interactions between different microbial species as well as with host cells.Deciphering such a molecular dialect will be fundamental to our understanding of host-microbe interactions in health and disease and may prove useful for the design of new therapeutic strategies that target these mechanisms of communication.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada.

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The mammalian gut microbiota is required for full inhibition of Salmonella invasion gene expression. (A) Molecules were extracted from feces of 129S1/SvImJ Nramp1−/− mice using ethyl acetate, as described in the text. Animals were then treated with 20 mg of streptomycin through oral gavage, and feces were collected and extracted again, 24 h after treatment. Salmonella was grown in LB broth with or without the addition of the dried extracts, and hilA expression was tested through RT-PCR. Results shown are the averages of 5 to 6 measurements, and bars represent the standard errors of the means. (B) Feces from conventionally raised as well as germfree Swiss Webster mice were collected and extracted with ethyl acetate, as described in the text. Salmonella was grown in LB broth with or without the addition of the dried extracts, and hilA expression was tested through RT-PCR. Results shown are the averages of 3 to 5 measurements, and bars represent the standard errors of the means. Untr., samples collected before antibiotic treatment; Strep., samples collected after streptomycin treatment; MPF, murine-pathogen-free animals (conventionally raised); GF, germfree animals. *, P < 0.04; **, P < 0.003; ***, P < 0.002.
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fig5: The mammalian gut microbiota is required for full inhibition of Salmonella invasion gene expression. (A) Molecules were extracted from feces of 129S1/SvImJ Nramp1−/− mice using ethyl acetate, as described in the text. Animals were then treated with 20 mg of streptomycin through oral gavage, and feces were collected and extracted again, 24 h after treatment. Salmonella was grown in LB broth with or without the addition of the dried extracts, and hilA expression was tested through RT-PCR. Results shown are the averages of 5 to 6 measurements, and bars represent the standard errors of the means. (B) Feces from conventionally raised as well as germfree Swiss Webster mice were collected and extracted with ethyl acetate, as described in the text. Salmonella was grown in LB broth with or without the addition of the dried extracts, and hilA expression was tested through RT-PCR. Results shown are the averages of 3 to 5 measurements, and bars represent the standard errors of the means. Untr., samples collected before antibiotic treatment; Strep., samples collected after streptomycin treatment; MPF, murine-pathogen-free animals (conventionally raised); GF, germfree animals. *, P < 0.04; **, P < 0.003; ***, P < 0.002.

Mentions: Collectively, our results showed that the human gut metabolome contains a molecule (or molecules) that acts as a strong inhibitor of Salmonella host cell invasion. In order to determine if this is specific to the human gut metabolome or a conserved feature among mammals, we tested the effect of molecules from the murine gut metabolome on Salmonella invasion gene expression during late logarithmic growth. Fresh feces of 129S1/SvImJ Nramp1−/− and Swiss Webster mice were extracted essentially as described for human samples and tested for effects on hilA expression. The results showed that the phenotype of hilA repression elicited by the gut metabolome is not exclusive to humans; fecal extracts from murine feces were also strong repressors of hilA (Fig. 5).


Antivirulence activity of the human gut metabolome.

Antunes LC, McDonald JA, Schroeter K, Carlucci C, Ferreira RB, Wang M, Yurist-Doutsch S, Hira G, Jacobson K, Davies J, Allen-Vercoe E, Finlay BB - MBio (2014)

The mammalian gut microbiota is required for full inhibition of Salmonella invasion gene expression. (A) Molecules were extracted from feces of 129S1/SvImJ Nramp1−/− mice using ethyl acetate, as described in the text. Animals were then treated with 20 mg of streptomycin through oral gavage, and feces were collected and extracted again, 24 h after treatment. Salmonella was grown in LB broth with or without the addition of the dried extracts, and hilA expression was tested through RT-PCR. Results shown are the averages of 5 to 6 measurements, and bars represent the standard errors of the means. (B) Feces from conventionally raised as well as germfree Swiss Webster mice were collected and extracted with ethyl acetate, as described in the text. Salmonella was grown in LB broth with or without the addition of the dried extracts, and hilA expression was tested through RT-PCR. Results shown are the averages of 3 to 5 measurements, and bars represent the standard errors of the means. Untr., samples collected before antibiotic treatment; Strep., samples collected after streptomycin treatment; MPF, murine-pathogen-free animals (conventionally raised); GF, germfree animals. *, P < 0.04; **, P < 0.003; ***, P < 0.002.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4128352&req=5

fig5: The mammalian gut microbiota is required for full inhibition of Salmonella invasion gene expression. (A) Molecules were extracted from feces of 129S1/SvImJ Nramp1−/− mice using ethyl acetate, as described in the text. Animals were then treated with 20 mg of streptomycin through oral gavage, and feces were collected and extracted again, 24 h after treatment. Salmonella was grown in LB broth with or without the addition of the dried extracts, and hilA expression was tested through RT-PCR. Results shown are the averages of 5 to 6 measurements, and bars represent the standard errors of the means. (B) Feces from conventionally raised as well as germfree Swiss Webster mice were collected and extracted with ethyl acetate, as described in the text. Salmonella was grown in LB broth with or without the addition of the dried extracts, and hilA expression was tested through RT-PCR. Results shown are the averages of 3 to 5 measurements, and bars represent the standard errors of the means. Untr., samples collected before antibiotic treatment; Strep., samples collected after streptomycin treatment; MPF, murine-pathogen-free animals (conventionally raised); GF, germfree animals. *, P < 0.04; **, P < 0.003; ***, P < 0.002.
Mentions: Collectively, our results showed that the human gut metabolome contains a molecule (or molecules) that acts as a strong inhibitor of Salmonella host cell invasion. In order to determine if this is specific to the human gut metabolome or a conserved feature among mammals, we tested the effect of molecules from the murine gut metabolome on Salmonella invasion gene expression during late logarithmic growth. Fresh feces of 129S1/SvImJ Nramp1−/− and Swiss Webster mice were extracted essentially as described for human samples and tested for effects on hilA expression. The results showed that the phenotype of hilA repression elicited by the gut metabolome is not exclusive to humans; fecal extracts from murine feces were also strong repressors of hilA (Fig. 5).

Bottom Line: Importance: Microbes can communicate through the production and sensing of small molecules.Within the complex ecosystem formed by commensal microbes living in and on the human body, it is likely that these molecular messages are used extensively during the interactions between different microbial species as well as with host cells.Deciphering such a molecular dialect will be fundamental to our understanding of host-microbe interactions in health and disease and may prove useful for the design of new therapeutic strategies that target these mechanisms of communication.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada.

Show MeSH
Related in: MedlinePlus