Endogenous viral elements inserted in host genomes are often regarded as inert relics of past infections. Whether they can retain infective potential and contribute to active viral cycles has remained largely unresolved. Here we demonstrate that giant viral elements in the multicellular alga Ectocarpus can reactivate and drive productive viral infections. Using long-read...
Microbiota-accessible carbohydrates modulate host immunity by shaping gut microbial composition and metabolism. However, their role in modulating the microbiota to influence allergic responses is unclear. Here we show that a widely used antidiabetic agent, the α-glucosidase inhibitor acarbose, redirects dietary carbohydrate utilization by gut bacteria to suppress mast-cell...
Broadly neutralizing antibodies (bnAbs) are promising agents for HIV-1 treatment and prevention. However, the genetic barriers and mutational pathways to viral resistance, which can limit therapeutic antibody utility, remain poorly defined. Here we developed a medium-to-high throughput approach to determine the mutations that confer resistance to neutralization by the bnAbs...
The ongoing census of microbial life is hampered by disparate sampling across Earth’s habitats, challenges in isolating uncultivated organisms, limited resolution in taxonomic marker gene amplicons and incomplete recovery of metagenome-assembled genomes. Here we quantify discoverable Bacterial and Archaeal diversity in a comprehensive, curated cross-habitat dataset of 92,187...
Simultaneous prescription of multiple drugs is widespread in medicine. Although the gut microbiome is implicated in drug responses, its role in mediating drug–drug interactions is unexplored. Catechol-O-methyltransferase inhibitors (COMT-I), a class of drugs used alongside levodopa (L-DOPA) to treat Parkinson’s disease symptoms, can alter microbiome composition in patients. Here...
The malaria elimination programme in Kayin State (Myanmar) uses malaria posts for rapid detection and treatment, together with mass drug administration in high-transmission villages, which has reduced transmission by 97%. Here we examine the impact of control on parasite genomic parameters to inform future control efforts. Using 2,270 genome-sequenced Plasmodium falciparum...
Bacteria use immune systems to detect and defend against mobile genetic elements including phages. Gene transfer agents (GTAs) are domesticated prophages with phage-like characteristics including the ability to induce host cell lysis for gene transfer. Whether GTAs elicit or avoid bacterial immune systems is poorly understood. Here, a transposon mutagenesis with deep sequencing...
Shotgun metagenomics can provide both taxonomic and functional insights, but benchmarking is necessary to determine the sequencing depth appropriate for specific analyses. Here we used complex mixtures of DNA from cultured bacteria and analysed taxonomic composition, strain-level resolution and functional profiles at up to 11 sequencing depths (0.1–50.0 Gb). Reference-based...
Carbohydrate-active enzymes (CAZymes) are crucial for digesting glycans, but tools for CAZyme profiling and interpretation of substrate preferences in microbiome data are lacking. Here we develop a CAZyme profiler called Cayman (Carbohydrate Active Enzymes Profiling of Metagenomes) and a hierarchical substrate annotation scheme for use with genomic or shotgun metagenomic datasets...
Coexisting strains of the same species within metagenomic data pose a substantial challenge to inferring transmission of pathogenic and commensal microbes. Here we present TRAnsmision Clustering of Strains (TRACS), a highly accurate algorithm for estimating genetic distances between strains at the level of individual single nucleotide polymorphisms, which is robust to intra...
Microbial coexistence in complex communities requires mechanisms that minimize competition and optimize resource use. However, the mechanisms by which these ecological strategies are executed remain poorly understood. Here we show that bacteria modulate protein abundance in response to specific community members, reducing functional redundancy and promoting metabolic...
Directed evolution methods face trade-offs between the control of discrete approaches and the throughput of modern continuous systems. Here, we engineered a method called lytic selection and evolution (LySE) for near-continuous evolution of bacterial gene clusters while maintaining discrete checkpoints. We developed a hypermutagenic T7 DNA polymerase variant fused to a dual...
Arthritogenic alphaviruses, including chikungunya virus (CHIKV), Mayaro virus and Ross River virus, cause long-lasting musculoskeletal pain and inflammation. However, the mechanisms driving chronic disease remain unclear. Here, we used single-cell RNA sequencing, spatial transcriptomics and flow cytometry to investigate joint-associated tissues in alphavirus-infected mice at a...
Homarine (N-methylpicolinic acid) is a ubiquitous marine metabolite produced by phytoplankton and noted for its infochemical properties among marine animals, yet its microbial degradation pathways are uncharacterized. Here we identify a conserved operon (homABCDER) that mediates homarine catabolism in bacteria using comparative transcriptomics, mutagenesis and targeted knockouts...
During weaning, the transition to solid food diversifies the gut microbiome, triggering a programmed immune response critical for long-lasting mucosal immunity. Previous work showed that the gut microbiome mediates epigenetic development in intestinal stem cells (ISCs) during suckling, but what happens during weaning is unclear. Here, genome-wide profiling revealed that weaning...
Azithromycin is a widely used antibiotic and was frequently used to treat hospitalized patients during the COVID-19 pandemic. The impact of empiric azithromycin use on the respiratory microbiome in patients with viral respiratory infections is unclear. Here we used longitudinal metatranscriptomics on nasal swabs from a prospective multicentre cohort of 1,164 patients hospitalized...
Infant gut microbiome development is strongly impacted by breastmilk and human milk oligosaccharides (HMOs), which can protect preterm infants against pathologies including necrotizing enterocolitis. HMO metabolism in bifidobacteria is well characterized and linked to health outcomes, but the scope of HMO-utilizing species remains unclear. Here, using a combination of genomics...
The emergence of SARS-CoV-2 Omicron variants has led to viral escape from many clinically approved monoclonal antibodies (mAbs) due to rapid evolution of the receptor-binding domain (RBD). Co-circulation of SARS-CoV-2 variants with unique sets of antigenic substitutions has further complicated therapeutic mAb discovery. New approaches are needed to rapidly discover and...
Yellow fever virus (YFV) continues to threaten human and wildlife populations in the Americas, yet its transmission at the forest–urban interface remains unclear. Here we integrate ground- and canopy-level mosquito surveillance, systematic monitoring of non-human primate carcasses and viral metagenomics to describe the dynamics of a sylvatic YFV outbreak in a 186-hectare Atlantic...