Nature Microbiology最新文献

Diet, microbiome, inflammation and host genetics have been linked to colorectal cancer development; however, it is not clear whether and how these factors interact to promote carcinogenesis. Here we used Il10^−/− mice colonized with bacteria previously associated with colorectal cancer: enterotoxigenic Bacteroides fragilis, Helicobacter hepaticus or colibactin-producing (polyketide synthase-positive (pks⁺)) Escherichia coli and fed either a low-carbohydrate (LC) diet deficient in soluble fibre, a high-fat and high-sugar diet, or a normal chow diet. Colonic polyposis was increased in mice colonized with pks⁺ E. coli and fed the LC diet. Mechanistically, mucosal inflammation was increased in the LC-diet-fed mice, leading to diminished colonic PPAR-γ signalling and increased luminal nitrate levels. This promoted both pks⁺ E. coli growth and colibactin-induced DNA damage. PPAR-γ agonists or supplementation with dietary soluble fibre in the form of inulin reverted inflammatory and polyposis phenotypes. The pks⁺ E. coli also induced more polyps in mismatch-repair-deficient mice by inducing a senescence-associated secretory phenotype. Moreover, oncogenic effects were further potentiated by inflammatory triggers in the mismatch-repair-deficient model. These data reveal that diet and host genetics influence the oncogenic potential of a common bacterium.

More than 70% of the human population lives within five kilometres of a natural water feature. These aquatic ecosystems are heavily used for resource provision and recreation, and represent the interface between human populations and aquatic microbiomes, which can sometimes negatively impact human health. Diverse species of endemic aquatic microorganisms, including toxic microalgae and pathogenic bacteria, can be harmful to humans. Aquatic ecosystems are also subject to intrusions of allochthonous pathogenic microorganisms through pollution and runoff. Notably, environmental processes that amplify the abundance and impact of harmful aquatic microorganisms are occurring with increasing frequency owing to climate change. For instance, increases in water temperature stimulate outbreaks of pathogenic and toxic species, whereas more intense precipitation events escalate microbial contamination from stormwater discharge. In this Perspective we discuss the influence of aquatic microbiomes on the health and economies of human populations and examine how climate change is increasing these impacts.

One-carbon feedstocks such as formate could be promising renewable substrates for sustainable microbial production of food, fuels and chemicals. Here we replace the native energy-inefficient Calvin–Benson–Bassham cycle in Cupriavidus necator with the more energy-efficient reductive glycine pathway for growth on formate and CO₂. In chemostats, our engineered strain reached a 17% higher biomass yield than the wild type and a yield higher than any natural formatotroph using the Calvin cycle. This shows the potential of synthetic metabolism to realize sustainable, bio-based production.

Bacteriophages constitute one of the largest reservoirs of genes of unknown function in the biosphere. Even in well-characterized phages, the functions of most genes remain unknown. Experimental approaches to study phage gene fitness and function at genome scale are lacking, partly because phages subvert many modern functional genomics tools. Here we leverage RNA-targeting dCas13d to selectively interfere with protein translation and to measure phage gene fitness at a transcriptome-wide scale. We find CRISPR Interference through Antisense RNA-Targeting (CRISPRi-ART) to be effective across phage phylogeny, from model ssRNA, ssDNA and dsDNA phages to nucleus-forming jumbo phages. Using CRISPRi-ART, we determine a conserved role of diverse rII homologues in subverting phage Lambda RexAB-mediated immunity to superinfection and identify genes critical for phage fitness. CRISPRi-ART establishes a broad-spectrum phage functional genomics platform, revealing more than 90 previously unknown genes important for phage fitness.

Correction to: Nature Microbiology https://doi.org/10.1038/s41564-024-01918-0, published online 4 February 2025.

Host factors that are involved in modulating cellular vesicular trafficking of virus progeny could be potential antiviral drug targets. ADP-ribosylation factors (ARFs) are GTPases that regulate intracellular vesicular transport upon GTP binding. Here we demonstrate that genetic depletion of ARF4 suppresses viral infection by multiple pathogenic RNA viruses including Zika virus (ZIKV), influenza A virus (IAV) and SARS-CoV-2. Viral infection leads to ARF4 activation and virus production is rescued upon complementation with active ARF4, but not with inactive mutants. Mechanistically, ARF4 deletion disrupts translocation of virus progeny into the Golgi complex and redirects them for lysosomal degradation, thereby blocking virus release. More importantly, peptides targeting ARF4 show therapeutic efficacy against ZIKV and IAV challenge in mice by inhibiting ARF4 activation. Our findings highlight the role of ARF4 during viral infection and its potential as a broad-spectrum antiviral target for further development.