Genome-scale resources in the infant gut symbiont Bifidobacterium breve reveal genetic determinants of colonization and host-microbe interactions.

Bifidobacteria represent a dominant constituent of human gut microbiomes during infancy, influencing nutrition, immune development, and resistance to infection. Despite interest in bifidobacteria as a live biotic therapy, our understanding of colonization, host-microbe interactions, and the health-promoting effects of bifidobacteria is limited. To address these major knowledge gaps, we used a large-scale genetic approach to create a mutant fitness compendium in Bifidobacterium breve.

High-throughput identification of gut microbiome-dependent metabolites.

A significant hurdle that has limited progress in microbiome science has been identifying and studying the diverse set of metabolites produced by gut microbes. Gut microbial metabolism produces thousands of difficult-to-identify metabolites, which present a challenge to study their roles in host biology. In recent years, mass spectrometry-based metabolomics has become one of the core technologies for identifying small metabolites.

Randomly barcoded transposon mutant libraries for gut commensals II: Applying libraries for functional genetics.

The critical role of the intestinal microbiota in human health and disease is well recognized. Nevertheless, there are still large gaps in our understanding of the functions and mechanisms encoded in the genomes of most members of the gut microbiota. Genome-scale libraries of transposon mutants are a powerful tool to help us address this gap.

A mutant fitness compendium in Bifidobacteria reveals molecular determinants of colonization and host-microbe interactions.

Bifidobacteria commonly represent a dominant constituent of human gut microbiomes during infancy, influencing nutrition, immune development, and resistance to infection. Despite interest as a probiotic therapy, predicting the nutritional requirements and health-promoting effects of Bifidobacteria is challenging due to major knowledge gaps. To overcome these deficiencies, we used large-scale genetics to create a compendium of mutant fitness in ().

Rapid Multivariate Analysis Approach to Explore Differential Spatial Protein Profiles in Tissue.

Spatially targeted proteomics analyzes the proteome of specific cell types and functional regions within tissue. While spatial context is often essential to understanding biological processes, interpreting sub-region-specific protein profiles can pose a challenge due to the high-dimensional nature of the data. Here, we develop a multivariate approach for rapid exploration of differential protein profiles acquired from distinct tissue regions and apply it to analyze a published spatially targeted proteomics data set collected from -infected murine kidney, 4 and 10 days postinfection.

Multimodal Imaging Mass Spectrometry of Murine Gastrointestinal Tract with Retained Luminal Content.

The gastrointestinal tract, including luminal content, harbors a complex mixture of microorganisms, host dietary content, and immune factors. Existing imaging approaches remove luminal content and only visualize small regions of the GI tract. Here, we demonstrate a workflow for multimodal imaging using matrix-assisted laser desorption/ionization imaging mass spectrometry, autofluorescence, and bright field microscopy for mapping intestinal tissue and luminal content.

Clostridioides difficile infection induces a rapid influx of bile acids into the gut during colonization of the host.

Clostridioides difficile is the leading cause of nosocomial intestinal infections in the United States. Ingested C. difficile spores encounter host bile acids and other cues that are necessary for germinating into toxin-producing vegetative cells.

Spatially Targeted Proteomics of the Host-Pathogen Interface during Staphylococcal Abscess Formation.

is a common cause of invasive and life-threatening infections that are often multidrug resistant. To develop novel treatment approaches, a detailed understanding of the complex host-pathogen interactions during infection is essential. This is particularly true for the molecular processes that govern the formation of tissue abscesses, as these heterogeneous structures are important contributors to staphylococcal pathogenicity.