The diversity and number of species present within microbial communities create the potential for a multitude interspecies metabolic interactions. Here, we develop, apply, experimentally test framework inferring mechanisms associated with We perform pairwise growth metabolome profiling co-cultures strains from model mouse microbiota. then apply our to dissect emergent behaviors that occur in co-culture. Based on one inferences this framework, identify interrogate an amino acid cross-feeding...

There is an emerging paradigm that the human microbiome central to many aspects of health and may have a role in preventing enteric infection. Entamoeba histolytica major cause amebic diarrhea developing countries. It colonizes colon lumen close proximity gut microbiota. Interestingly, not all individuals are equally susceptible E. Therefore, as microbiota highly variable within individuals, we sought determine if component could regulate susceptibility In studies utilizing murine model,...

Commentary26 August 2020Open Access Community standards to facilitate development and address challenges in metabolic modeling Maureen A Carey orcid.org/0000-0003-2890-5445 Division of Infectious Diseases International Health, Department Medicine, University Virginia, Charlottesville, VA, USA Search for more papers by this author Andreas Dräger orcid.org/0000-0002-1240-5553 Computational Systems Biology Infection Antimicrobial-Resistant Pathogens, Institute Biomedical Informatics (IBMI),...

Abstract Background The protozoan parasites in the Cryptosporidium genus cause both acute diarrheal disease and subclinical (ie, nondiarrheal) disease. It is unclear if microbiota can influence manifestation of diarrhea during a infection. Methods To characterize role gut cryptosporidiosis, microbiome composition surveillance Cryptosporidium-positive fecal samples from 72 infants was evaluated using 16S ribosomal RNA gene sequencing. Additionally, prior to infection examined test whether...

Malaria remains a major public health burden and resistance has emerged to every antimalarial on the market, including frontline drug, artemisinin. Our limited understanding of Plasmodium biology hinders elucidation mechanisms. In this regard, systems approaches can facilitate integration existing experimental knowledge further these mechanisms.Here, we developed novel genome-scale metabolic network reconstruction, iPfal17, asexual blood-stage P. falciparum parasite expand our changes that...

Construction and analysis of genome-scale metabolic models (GEMs) is a well-established systems biology approach that can be used to predict growth phenotypes. The ability GEMs produce mechanistic insight into microbial ecological processes makes them appealing tools open range exciting opportunities in microbiome research.

Establishing commensal dysbiosis, defined as an inflammatory gut microbiome with low biodiversity, before breast tumor initiation, enhances early dissemination of hormone receptor-positive (HR+) mammary cells. Here, we sought to determine whether cellular changes occurring in normal tissues, initiation and response enhanced HR+ tumors. Commensal dysbiosis increased both the frequency profibrogenicity mast cells normal, non-tumor-bearing a phenotypic change that persisted after implantation....

Antimalarial resistance is a major obstacle in the eradication of human malaria parasite, Plasmodium falciparum. Genome amplifications, type DNA copy number variation (CNV), facilitate overexpression drug targets and contribute to parasite survival. Long monomeric A/T tracks are found at breakpoints many resistance-conferring CNVs. We hypothesize that other proximal sequence features, such as hairpins, act with trigger CNV formation. By adapting analysis pipeline investigate previously...

Protozoan parasites cause diverse diseases with large global impacts. Research on the pathogenesis and biology of these organisms is limited by economic experimental constraints. Accordingly, studies one parasite are frequently extrapolated to infer knowledge about another parasite, across within genera. Model in vitro or vivo systems used enhance manipulability, but generally use species related to, yet distinct from, clinically relevant causal pathogen. Characterization functional...

Molecular characterization of pathogens such as the malaria parasite can lead to improved biological understanding and novel treatment strategies. However, distinctive biology Plasmodium parasite, including its repetitive genome requirement for growth within a host cell, hinders progress toward these goals. Untargeted metabolomics is promising approach learn about pathogen biology. By measuring many small molecules in at once, we gain better important pathways that contribute parasite’s...

Malaria is a major global health problem, with the Plasmodium falciparum protozoan parasite causing most severe form of disease. Prevalence drug-resistant P. highlights need to understand biology resistance and identify novel combination therapies that are effective against resistant parasites. Resistance has compromised therapeutic use many antimalarial drugs, including chloroquine, limited our ability treat malaria across world. Fortunately, chloroquine comes at fitness cost parasite; this...

ABSTRACT Standardization of data and models facilitates effective communication, especially in computational systems biology. However, both the development consistent use standards resources remains challenging. As a result, amount, quality, format information contained within biology are not therefore present challenges for widespread communication. Here, we focused on these standards, resources, field metabolic modeling by conducting community-wide survey. We used this feedback to (1)...

Abstract Metabolic interactions among species are ubiquitous in nature, and the fitness costs benefits they impose often reinforce stabilize them over time. These of particular importance human gut, where have functions ranging from enhancing digestion to preventing (or exacerbating) infections. The diversity sheer number present lead potential for a multitude metabolic occur. However, identifying mechanism consequences between even two is incredibly challenging. Here, we develop, apply,...

Previous data obtained in our laboratory suggested that there may be constitutive signaling through the myeloid differentiation primary response gene 88 (Myd88)-dependent cascade murine mammary carcinoma. Here, we extended these findings by showing that, absence of an added Toll-like receptor (TLR) agonist, myddosome complex was preformed 4T1 tumor cells, and Myd88 influenced cytoplasmic extracellular signal–regulated kinase (Erk)1/Erk2 levels, nuclear levels factor-kappaB (NFκB) signal...

Abstract Protozoan parasites cause diverse diseases with large global impacts. Research on the pathogenesis and biology of these organisms is limited by economic experimental constraints. Accordingly, studies one parasite are frequently extrapolated to infer knowledge about another parasite, across within genera. Model in vitro or vivo systems used enhance manipulability, but generally use species related to, yet distinct from, clinically relevant causal pathogen. Characterization functional...

ABSTRACT BACKGROUND Malaria remains a major public health burden and resistance has emerged to every antimalarial on the market, including frontline drug artemisinin. Our limited understanding of Plasmodium biology hinders elucidation mechanisms. In this regard, systems approaches can facilitate integration existing experimental knowledge further these RESULTS Here, we developed novel genome-scale metabolic network reconstruction, iPfal17, asexual blood-stage P. falciparum parasite expand...

Abstract Cryptosporidium species are a major cause of diarrhea and associated with growth failure. There is currently only limited knowledge the parasite's genomic variability. We report analysis parvum isolated from Bangladeshi infants reanalysis sequences United Kingdom. Human isolates both locations shared 154 variants not present in cattle-derived reference genome, suggesting host-specific adaptation parasite. Remarkably 34.6% single-nucleotide polymorphisms unique to human were...

ABSTRACT Background The protozoan parasites in the Cryptosporidium genus cause both acute diarrheal disease and subclinical (i.e. non-diarrheal) disease. It is unclear if microbiota can influence manifestation of diarrhea during a infection. Methods To characterize role gut cryptosporidiosis, microbiome composition surveillance -positive fecal samples was evaluated using 16S rRNA gene sequencing. Additionally, prior to infection examined test whether preexisting profile could phenotype....

ABSTRACT Metabolomics is increasingly popular for the study of many pathogens. For malaria parasite, Plasmodium falciparum , both targeted and untargeted metabolite detection has improved our understanding pathogenesis, host-parasite interactions, antimalarial drug treatment resistance. However, purification analysis procedures performing metabolomics on intracellular pathogens have not been explored. Here, we investigate impact host contamination metabolome when preparing samples using...

Abstract Malaria is a major global health problem, with the Plasmodium falciparum protozoan parasite causing most severe form of disease. Prevalence drug-resistant P. highlights need to understand biology resistance and identify novel combination therapies that are effective against resistant parasites. Resistance has compromised therapeutic use many antimalarial drugs, including chloroquine, limited our ability treat malaria across world. Fortunately, chloroquine comes at fitness cost...