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Functional Characteristics of the Gut Microbiome in C57BL/6 Mice Differentially Susceptible to Plasmodium yoelii

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ABSTRACT

C57BL/6 mice are widely used for in vivo studies of immune function and metabolism in mammals. In a previous study, it was observed that when C57BL/6 mice purchased from different vendors were infected with Plasmodium yoelii, a causative agent of murine malaria, they exhibited both differential immune responses and significantly different parasite burdens: these patterns were reproducible when gut contents were transplanted into gnotobiotic mice. To gain insight into the mechanism of resistance, we removed whole ceca from mice purchased from two vendors, Taconic Biosciences (low parasitemia) and Charles River Laboratories (high parasitemia), to determine the combined host and microflora metabolome and metatranscriptome. With the exception of two Charles River samples, we observed ≥90% similarity in overall bacterial gene expression within vendors and ≤80% similarity between vendors. In total 33 bacterial genes were differentially expressed in Charles River mice (p-value < 0.05) relative to the mice purchased from Taconic. Included among these, fliC, ureABC, and six members of the nuo gene family were overrepresented in microbiomes susceptible to more severe malaria. Moreover, 38 mouse genes were differentially expressed in these purported genetically identical mice. Differentially expressed genes included basigin, a cell surface receptor required for P. falciparum invasion of red blood cells. Differences in metabolite pools were detected, though their relevance to malaria infection, microbial community activity, or host response is not yet understood. Our data have provided new targets that may connect gut microbial activity to malaria resistance and susceptibility phenotypes in the C57BL/6 model organism.

No MeSH data available.


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Relative abundance of Bacterial phyla and total Archaea, Eukarya, and virus reads. Read counts normalized by library size from the samples in each group. Blue bars represent abundance in mice purchased from Taconic Biosciences. Red bars represent abundance in mice purchased from Charles River Laboratories. Error bars represent standard deviation. Data (mean ± SD) are from n = 5 Tac and n = 6 CR mice.
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Figure 2: Relative abundance of Bacterial phyla and total Archaea, Eukarya, and virus reads. Read counts normalized by library size from the samples in each group. Blue bars represent abundance in mice purchased from Taconic Biosciences. Red bars represent abundance in mice purchased from Charles River Laboratories. Error bars represent standard deviation. Data (mean ± SD) are from n = 5 Tac and n = 6 CR mice.

Mentions: The phylogenetic makeup of the cecal microbial community as determined by metatranscriptomic analysis is represented in Figure 2. The microbial community transcriptional profile is dominated by the bacterial phyla Firmicutes and Bacteroidetes, the reads from which make up an average of 90.1% ± 6.3 of each sample. The next most abundant source of transcripts originate in Proteobacteria at 3.2% ± 0.20 of reads, followed by Actinobacteria, 1.7% ± 0.16, and Fusobacteria, 0.53% ± 0.03. Within the phylum Bacteroidetes, families Bacteroidaceae and Porphyromonadaceae are most prevalent, 46.7% and 51.1% of the phylum, respectively. The Firmicutes portion of the community is split predominantly between orders Lactobacillales and Clostridiales, 8.9 and 82.5% of the phylum, respectively. The MG-RAST pipeline identified 0.04% ± 0.007 of the reads as being of viral origin, all of which were bacteriophage. Archaea made up 0.24% ± 0.009 of the transcripts, with the Euryarchaeota dominating at 92.3% of the Archaeal reads.


Functional Characteristics of the Gut Microbiome in C57BL/6 Mice Differentially Susceptible to Plasmodium yoelii
Relative abundance of Bacterial phyla and total Archaea, Eukarya, and virus reads. Read counts normalized by library size from the samples in each group. Blue bars represent abundance in mice purchased from Taconic Biosciences. Red bars represent abundance in mice purchased from Charles River Laboratories. Error bars represent standard deviation. Data (mean ± SD) are from n = 5 Tac and n = 6 CR mice.
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Figure 2: Relative abundance of Bacterial phyla and total Archaea, Eukarya, and virus reads. Read counts normalized by library size from the samples in each group. Blue bars represent abundance in mice purchased from Taconic Biosciences. Red bars represent abundance in mice purchased from Charles River Laboratories. Error bars represent standard deviation. Data (mean ± SD) are from n = 5 Tac and n = 6 CR mice.
Mentions: The phylogenetic makeup of the cecal microbial community as determined by metatranscriptomic analysis is represented in Figure 2. The microbial community transcriptional profile is dominated by the bacterial phyla Firmicutes and Bacteroidetes, the reads from which make up an average of 90.1% ± 6.3 of each sample. The next most abundant source of transcripts originate in Proteobacteria at 3.2% ± 0.20 of reads, followed by Actinobacteria, 1.7% ± 0.16, and Fusobacteria, 0.53% ± 0.03. Within the phylum Bacteroidetes, families Bacteroidaceae and Porphyromonadaceae are most prevalent, 46.7% and 51.1% of the phylum, respectively. The Firmicutes portion of the community is split predominantly between orders Lactobacillales and Clostridiales, 8.9 and 82.5% of the phylum, respectively. The MG-RAST pipeline identified 0.04% ± 0.007 of the reads as being of viral origin, all of which were bacteriophage. Archaea made up 0.24% ± 0.009 of the transcripts, with the Euryarchaeota dominating at 92.3% of the Archaeal reads.

View Article: PubMed Central - PubMed

ABSTRACT

C57BL/6 mice are widely used for in vivo studies of immune function and metabolism in mammals. In a previous study, it was observed that when C57BL/6 mice purchased from different vendors were infected with Plasmodium yoelii, a causative agent of murine malaria, they exhibited both differential immune responses and significantly different parasite burdens: these patterns were reproducible when gut contents were transplanted into gnotobiotic mice. To gain insight into the mechanism of resistance, we removed whole ceca from mice purchased from two vendors, Taconic Biosciences (low parasitemia) and Charles River Laboratories (high parasitemia), to determine the combined host and microflora metabolome and metatranscriptome. With the exception of two Charles River samples, we observed ≥90% similarity in overall bacterial gene expression within vendors and ≤80% similarity between vendors. In total 33 bacterial genes were differentially expressed in Charles River mice (p-value < 0.05) relative to the mice purchased from Taconic. Included among these, fliC, ureABC, and six members of the nuo gene family were overrepresented in microbiomes susceptible to more severe malaria. Moreover, 38 mouse genes were differentially expressed in these purported genetically identical mice. Differentially expressed genes included basigin, a cell surface receptor required for P. falciparum invasion of red blood cells. Differences in metabolite pools were detected, though their relevance to malaria infection, microbial community activity, or host response is not yet understood. Our data have provided new targets that may connect gut microbial activity to malaria resistance and susceptibility phenotypes in the C57BL/6 model organism.

No MeSH data available.


Related in: MedlinePlus