Research Briefing

In 22 patients with auto-brewery syndrome, we found enrichment of gut bacterial genes in metabolic pathways associated with ethanol production. Treatment with faecal microbiota transplantation in one patient led to improvement in symptoms that correlated with changes in gut microbiota composition and improved metabolic function.

A comprehensive assessment of how transformation of dietary nutrients by the gut microbiota influences host health is needed. Systematic integration of 5,554 global gut metagenomes and various biochemical databases reveals how dietary phytonutrients are biotransformed by the gut microbiota and their enzymes, and how these biotransformations relate to human health.

A zoonotic Streptococcus species achieves massive proliferation in the brain, leading to potentially lethal meningitis and severe brain injury. This robust growth depends on a species-specific promoter that induces constitutive transcription of a phosphotransferase system that facilitates carbohydrate uptake and prevents the bacterial stringent response in the low-glucose environment of the cerebrospinal fluid.

We uncover hundreds of inhibitory interactions between industrial and agricultural chemicals and gut bacteria. Systematic genetic analyses reveal bacterial survival mechanisms against pollutants and their commonality with antibiotic resistance. Our data enable machine learning-based predictive toxicology and make a case for considering antibacterial activity in chemical safety assessment.

By combining bioorthogonal non-canonical amino acid tagging, metaproteomics and stable isotope probing, we identified a rare and uncharacterized bacterium with a glycine-mediated metabolism for syntrophic acetate oxidation within an anaerobic microbiota. This approach shows promise to enrich proteins of rare and active microorganisms across diverse habitats to characterize their in situ ecophysiology.

A high-throughput screen that measures bacterial metabolism and host cell viability identified a host-directed compound (KL1) that reactivates intracellular bacteria that have developed antibiotic tolerance (persisters) by boosting their metabolism, which makes them susceptible to antibiotics again. KL1 enhances treatment efficacy across multiple pathogens without harming host cells.

Metabolic pathways are important for all biological processes, including host defence against pathogens. We show that activation of innate immune signalling is primed by oxaloacetate sensing through the cytosolic malate dehydrogenase MDH1, ensuring optimal production of type I interferons and host immune homeostasis in response to influenza virus infection.

Better knowledge of which fungal mutations give rise to antimicrobial resistance and by which mechanisms is key to improving treatment strategies and drug development. We assembled a comprehensive dataset of drug resistance mutations in fungal genomes and used it to uncover their diversity, conservation across species, impact on protein functions and potential for cross-resistance.

Deep, long-read metagenome sequencing of 154 soil and sediment samples from diverse habitats in Denmark enabled recovery of 4,894 high-quality and highly contiguous microbial genomes. The vast untapped microbial diversity in complex ecosystems can now be systematically explored, categorized and capitalized on.

A newly identified human cytomegalovirus cell entry complex couples the canonical envelope glycoprotein H with UL116 (a mimic of glycoprotein L) to incorporate the immune-evasion molecule UL141 into virions. This complex (named gH-associated tropism and entry (GATE)-3) facilitates infection of endothelial cells and is a promising target for vaccines.

Cyclic-di-AMP is a broadly conserved nucleotide second messenger that is critical for growth and virulence in Gram-positive bacteria. Genetic, cell biological and biophysical analyses reveal that cyclic-di-AMP functions to control cytoplasmic turgor pressure in response to cell wall stress. The reduction in turgor enables cells to withstand lysis.

This study revealed that typhoid toxin, a Salmonella Typhi virulence factor, causes encephalopathy by disrupting the blood–brain barrier (BBB). Using genetically engineered mouse models and an in vitro BBB system, we identified endothelial cells as the toxin’s primary target and showed that corticosteroids can mitigate the resulting BBB disruption.

A dataset of 2,997 metagenomes from 913 genetically diverse mice provides insights into microbiome interactions with ageing, dietary restriction, host genetics and longevity.

Phollow is an in vivo tagging approach for marking bacteriophages with fluorescent proteins while new virions are assembled in bacteria, enabling direct observation of phage outbreaks with single-virion resolution. Using Phollow to track phages in situ in model gut microbial communities uncovers spatiotemporal features of transmission dynamics that shape microbiomes.

Our study assessed the ability of existing influenza antivirals to treat severe A(H5N1) influenza in a mouse model. Results were dependent on drug, dosage and infection route but highlighted the need to explore further options for treatment.

Gene expression analyses and functional studies reveal that the salivary glands of mosquitoes have rhythmic genes, including those involved in bloodmeal digestion. In addition, the malaria parasite’s sporozoites show daily rhythms, which suggests that synchronized clocks among mosquitoes, parasites and the host enhance transmission efficiency.

Long-distance gene regulation is uncommon in bacteria, and its molecular mechanisms are unclear. Using a combination of structural, biochemical and single-molecule techniques, researchers revealed that KorB, a DNA-sliding clamp capable of traversing long genomic distances, is captured by KorA to form a stable transcriptional co-repressor complex on a bacterial plasmid.

Characterization of gut metagenomes from 21,561 volunteers on omnivore, vegetarian or vegan diets shows how major food groups may shape the gut microbiome not only through the selection of microbes that aid in digestion, but also through the acquisition of microbes from foods themselves.

A predictive model developed using machine learning, high-throughput sequencing of the microbiomes associated with seed tubers and drone imaging of the crops growing from the tubers can forecast the performance of potato plants based on the microbiome composition of their seed tubers. In addition, this model can identify the best microbial predictors of potato plant growth.

Researchers show that the dynamics of metabolomic rearrangement dictate the growth response of bacteria and fungi to rapid changes in temperature. Single-cell microscopy revealed a mechanism for transient memory of previous temperatures and indicated that these responses are generally conserved, advancing our understanding of microbial behaviour in fluctuating environments.