15 research outputs found
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Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis
Rheumatoid arthritis (RA) is a prevalent systemic autoimmune disease, caused by a combination of genetic and environmental factors. Animal models suggest a role for intestinal bacteria in supporting the systemic immune response required for joint inflammation. Here we performed 16S sequencing on 114 stool samples from rheumatoid arthritis patients and controls, and shotgun sequencing on a subset of 44 such samples. We identified the presence of Prevotella copri as strongly correlated with disease in new-onset untreated rheumatoid arthritis (NORA) patients. Increases in Prevotella abundance correlated with a reduction in Bacteroides and a loss of reportedly beneficial microbes in NORA subjects. We also identified unique Prevotella genes that correlated with disease. Further, colonization of mice revealed the ability of P. copri to dominate the intestinal microbiota and resulted in an increased sensitivity to chemically induced colitis. This work identifies a potential role for P. copri in the pathogenesis of RA. DOI: http://dx.doi.org/10.7554/eLife.01202.00
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Interactions of Microbes in Communities
Groups of microorganisms sharing an environment (microbial communities) are ubiquitous in nature. Microbial communities provide essential ecosystem services to other life on Earth by e.g., participating in global biogeochemical processes or interacting with a host’s immune system. Such microbes compete for scarce resources, modify an environment for their own purposes, actively war, and occasionally cooperate. Though numerous studies have surveyed the diversity of microbial life in different environments, few have determined the ways in which members of microbial communities interact with one another. Understanding the ways and means by which microbes interact is essential if we are to understand how microbial communities form, persist, and change over time. Knowledge of these processes will allow us to rationally design microbial communities to perform useful functions and predict how our actions might shift the balance of microbes in a community, and thus affect its function. In this work, we develop and apply novel methods for understanding microbial interactions
Recommended from our members
Interactions of Microbes in Communities
Groups of microorganisms sharing an environment (microbial communities) are ubiquitous in nature. Microbial communities provide essential ecosystem services to other life on Earth by e.g., participating in global biogeochemical processes or interacting with a host’s immune system. Such microbes compete for scarce resources, modify an environment for their own purposes, actively war, and occasionally cooperate. Though numerous studies have surveyed the diversity of microbial life in different environments, few have determined the ways in which members of microbial communities interact with one another. Understanding the ways and means by which microbes interact is essential if we are to understand how microbial communities form, persist, and change over time. Knowledge of these processes will allow us to rationally design microbial communities to perform useful functions and predict how our actions might shift the balance of microbes in a community, and thus affect its function. In this work, we develop and apply novel methods for understanding microbial interactions
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Monofluorophosphate is a selective inhibitor of respiratory sulfate-reducing microorganisms.
Despite the environmental and economic cost of microbial sulfidogenesis in industrial operations, few compounds are known as selective inhibitors of respiratory sulfate reducing microorganisms (SRM), and no study has systematically and quantitatively evaluated the selectivity and potency of SRM inhibitors. Using general, high-throughput assays to quantitatively evaluate inhibitor potency and selectivity in a model sulfate-reducing microbial ecosystem as well as inhibitor specificity for the sulfate reduction pathway in a model SRM, we screened a panel of inorganic oxyanions. We identified several SRM selective inhibitors including selenate, selenite, tellurate, tellurite, nitrate, nitrite, perchlorate, chlorate, monofluorophosphate, vanadate, molydate, and tungstate. Monofluorophosphate (MFP) was not known previously as a selective SRM inhibitor, but has promising characteristics including low toxicity to eukaryotic organisms, high stability at circumneutral pH, utility as an abiotic corrosion inhibitor, and low cost. MFP remains a potent inhibitor of SRM growing by fermentation, and MFP is tolerated by nitrate and perchlorate reducing microorganisms. For SRM inhibition, MFP is synergistic with nitrite and chlorite, and could enhance the efficacy of nitrate or perchlorate treatments. Finally, MFP inhibition is multifaceted. Both inhibition of the central sulfate reduction pathway and release of cytoplasmic fluoride ion are implicated in the mechanism of MFP toxicity
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Mechanisms of direct inhibition of the respiratory sulfate-reduction pathway by (per)chlorate and nitrate.
We investigated perchlorate (ClO(4)(-)) and chlorate (ClO(3)(-)) (collectively (per)chlorate) in comparison with nitrate as potential inhibitors of sulfide (H(2)S) production by mesophilic sulfate-reducing microorganisms (SRMs). We demonstrate the specificity and potency of (per)chlorate as direct SRM inhibitors in both pure cultures and undefined sulfidogenic communities. We demonstrate that (per)chlorate and nitrate are antagonistic inhibitors and resistance is cross-inducible implying that these compounds share at least one common mechanism of resistance. Using tagged-transposon pools we identified genes responsible for sensitivity and resistance in Desulfovibrio alaskensis G20. We found that mutants in Dde_2702 (Rex), a repressor of the central sulfate-reduction pathway were resistant to both (per)chlorate and nitrate. In general, Rex derepresses its regulon in response to increasing intracellular NADH:NAD(+) ratios. In cells in which respiratory sulfate reduction is inhibited, NADH:NAD(+) ratios should increase leading to derepression of the sulfate-reduction pathway. In support of this, in (per)chlorate or nitrate-stressed wild-type G20 we observed higher NADH:NAD(+) ratios, increased transcripts and increased peptide counts for genes in the core Rex regulon. We conclude that one mode of (per)chlorate and nitrate toxicity is as direct inhibitors of the central sulfate-reduction pathway. Our results demonstrate that (per)chlorate are more potent inhibitors than nitrate in both pure cultures and communities, implying that they represent an attractive alternative for controlling sulfidogenesis in industrial ecosystems. Of these, perchlorate offers better application logistics because of its inhibitory potency, solubility, relative chemical stability, low affinity for mineral cations and high mobility in environmental systems
The bilateral responsiveness between intestinal microbes and IgA
The immune system has developed strategies to maintain a homeostatic relationship with the resident microbiota. IgA is central in holding this relationship, as the most dominant immunoglobulin isotype at the mucosal surface of the intestine. Recent studies report a role for IgA in shaping the composition of the intestinal microbiota and exploit strategies to characterise IgA-binding bacteria for their inflammatory potential. We review these findings here, and place them in context of the current understanding of the range of microorganisms that contribute to the IgA repertoire and the pathways that determine the quality of the IgA response. We examine why only certain intestinal microbes are coated with IgA, and discuss how understanding the determinants of this specific responsiveness may provide insight into diseases associated with dysbiosis