6 research outputs found
microbeMASST: A Taxonomically-informed Mass Spectrometry Search Tool for Microbial Metabolomics Data
microbeMASST, a taxonomically informed mass spectrometry (MS) search tool, tackles limited microbial metabolite annotation in untargeted metabolomics experiments. Leveraging a curated database of >60,000 microbial monocultures, users can search known and unknown MS/MS spectra and link them to their respective microbial producers via MS/MS fragmentation patterns. Identification of microbe-derived metabolites and relative producers without a priori knowledge will vastly enhance the understanding of microorganismsâ role in ecology and human health
A Taxonomically-informed Mass Spectrometry Search Tool for Microbial Metabolomics Data
MicrobeMASST, a taxonomically-informed mass spectrometry (MS) search tool, tackles limited microbial metabolite annotation in untargeted metabolomics experiments. Leveraging a curated database of >60,000 microbial monocultures, users can search known and unknown MS/MS spectra and link them to their respective microbial producers via MS/MS fragmentation patterns. Identification of microbial-derived metabolites and relative producers, without a priori knowledge, will vastly enhance the understanding of microorganismsâ role in ecology and human health
Molecular understanding of fungal cell wall metabolism by gut Bacteroides
Ph. D. Thesis.The human gut is populated with a vast community of microbes, the microbiota.
The Bacteroidetes play a prominent role in the breakdown of complex
carbohydrates. Fungi are also normal members of the gut microbiota. Fungal cell
wall proteins are extensively mannosylated, forming a highly branched matrix of
mannan. Previous data from our lab show that the common gut bacterium,
Bacteroides thetaiotaomicron (Bt) degrades cell wall mannan from S. cerevisiae
via a selfish mechanism. Bt does this by releasing large oligosaccharides at the
cell surface, which are transported into the periplasmic space to be further
depolymerised.
Firstly, the degradation of mannan from a common human pathogen, Candida
albicans was investigated. Here, novel enzymes from the Glycoside Hydrolase
130 family, which target ÎČ-1,2-mannosidic linkages found in C. albicans mannan,
have been biochemically characterised. Bt was genetically manipulated to
examine its ability to utilise mannan from C. albicans. This work demonstrated that
degradation of C. albicans mannan in Bt requires an additional regulatory
mechanism.
Secondly, I discovered that another gut Bacteroides, B. salyersiae (Bs), degrades
yeast α-mannan in a mechanism contrasting to the âselfishâ strategy. Unlike Bt, Bs
releases a range of smaller manno-oligosaccharides into the extracellular milieu,
which are utilised as âpublic goodsâ by other members of the gut microbiota.
Biochemical characterisation of this alternative mechanism revealed that proteins
orchestrating mannan breakdown contain signals, targeting them for the
Bacteroidetes specific type 9 secretion system (T9SS). Our analysis revealed that
Bs directs at least 109 proteins of diverse functions to the T9SS, implicating its
role in a plethora of metabolic processes. This is the first description of T9SS in a
human gut Bacteroides. This work demonstrates that members of the microbiota
have developed multiple strategies for utilisation of the same carbon to survive in
a highly populated human gut
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Commensal bacteria promote type I interferon signaling to maintain immune tolerance in mice
Type I interferons (IFNs) exert a broad range of biological effects important in coordinating immune responses, which have classically been studied in the context of pathogen clearance. Yet, whether immunomodulatory bacteria operate through IFN pathways to support intestinal immune tolerance remains elusive. Here, we reveal that the commensal bacterium, Bacteroides fragilis, utilizes canonical antiviral pathways to modulate intestinal dendritic cells (DCs) and regulatory T cell (Treg) responses. Specifically, IFN signaling is required for commensal-induced tolerance as IFNAR1-deficient DCs display blunted IL-10 and IL-27 production in response to B. fragilis. We further establish that IFN-driven IL-27 in DCs is critical in shaping the ensuing Foxp3+ Treg via IL-27Rα signaling. Consistent with these findings, single-cell RNA sequencing of gut Tregs demonstrated that colonization with B. fragilis promotes a distinct IFN gene signature in Foxp3+ Tregs during intestinal inflammation. Altogether, our findings demonstrate a critical role of commensal-mediated immune tolerance via tonic type I IFN signaling
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microbeMASST: a taxonomically informed mass spectrometry search tool for microbial metabolomics data
microbeMASST, a taxonomically informed mass spectrometry (MS) search tool, tackles limited microbial metabolite annotation in untargeted metabolomics experiments. Leveraging a curated database of >60,000 microbial monocultures, users can search known and unknown MS/MS spectra and link them to their respective microbial producers via MS/MS fragmentation patterns. Identification of microbe-derived metabolites and relative producers without a priori knowledge will vastly enhance the understanding of microorganisms' role in ecology and human health