Volume 5 Issue 1, January 2020

As microbiome science expands, academic centres scramble to fill many needs, from service provider to industry liaison. A newly created network aims to share strategies and accelerate knowledge transfer, and invites others to join the efforts.

Baloxavir marboxil (BXM) represents a promising advance in antiviral chemotherapies for influenza infections. Identification of transmissible BXM-resistant strains in Japan may hit pause on widespread adoption of this therapy and could lead to revision of surveillance practices for emerging viruses.

Adding a flap on the top of an insecticide-treated bednet helps to intercept blood-seeking mosquitoes and allows a wider range of insecticides to be used together. Net buyers must now make a challenging decision for each target area: which net product will be most cost-effective, given the resistance in local vectors?

Two recent studies reveal a virus anti-defence strategy whereby large, ‘jumbo’ phages protect themselves from both restriction endonucleases and DNA-targeting CRISPR–Cas systems, but not from RNA-targeting ones, by encapsulating the phage genome inside the cell in a ‘nucleus’-like shell that is impenetrable for CRISPR effectors.

Metabolic adaptation plays a key role in determining the composition of microbial ecosystems. A new study shows that in the inflamed gut, pathogenic Enterobacteriaceae can reprogramme their metabolism towards diet-derived l-serine utilization to outcompete the resident microbiota and cause disease.

The host protein cyclophilin A binds to the HIV-1 capsid and its role in infection has long been enigmatic. A new study shows that this interaction protects the virus from inhibition by TRIM5α in physiologically relevant primary human cells.

This Review summarizes mechanisms by which hosts recognize pathogens and their effectors, and trigger downstream immune pathways.

Resistance to baloxavir marboxil, a recently approved drug to treat influenza infection, was thought to make the virus less fit. This study reports that resistant viruses isolated from Japanese patients have normal replicative abilities and pathogenicity in animal models and thus might spread in humans.

Electron micrographs show that mouse and rat segmented filamentous bacterium (SFB) unicellular intracellular offspring (IO) are flagellated and that flagellation occurs before IO release from SFB filaments.

The addition of a small net barrier above a standard bednet targets malaria vectors and—as these barriers are further distanced from sleepers—paves the way for the use of a wider range of insecticides to curtail malaria transmission.

This paper identifies a Serratia jumbo phage that, on infection, leads to the formation of a nucleus-like structure that protects phage DNA from CRISPR–Cas defence systems. However, the phage is still susceptible to CRISPR–Cas RNA targeting in the cytoplasm.

A consortium of four human gut microbiota species, including Eggerthella lenta, can convert plant-derived lignans into bioactive enterolignans via a five-step pathway, providing mechanistic insight into the production of these protective metabolites.

Hergenrother and colleagues develop a web portal to help predict key permeation aspects of query compounds using the eNTRy rules they recently developed. They use this approach to screen antibiotics that are effective against Gram-positive bacteria and engineer a modified version of a FabI inhibitor that is an effective Gram-negative antibiotic.

This work reports an analysis of primary and secondary immune responses in ten women infected with ZIKV for 224 days following an acute symptomatic Zika virus infection. CD4⁺ T-cell responses broadly targeted the whole Zika genome, whereas CD8⁺ T cells were strongly biased towards non-structural proteins.

The gut microbiota enhances murine norovirus infection in distal regions of the gut, but inhibits viral infection in the proximal small intestine via altered bile acid metabolism and consequent type III interferon production.

A modified mouse model that mimics human serum levels of biotin shows that inhibition of biotin synthesis can effectively treat infections caused by diverse antibiotic-resistant pathogens.

The cryo-electron microscopy structures of the cell-binding component of the Clostridioides difficile transferase toxin in different oligomeric states reveal the conformational changes undergone by the toxin while inserting into target membranes to form a pore.

Here, the authors use metabolomics and sequencing to assess changes in chemicals and microbial communities, including fungi and microeukaryotes, across an urbanization gradient in South America.

Members of the Enterobacteriaceae, including adherent invasive Escherichia coli, reprogram their metabolism to preferentially consume dietary serine during periods of inflammation in the gut to promote their growth and outcompete other microbiome members.

The combined use of genome sequencing, cultivation and phenotypic characterization of 79 globally distributed strains from the bacterial phylum Planctomycetes sheds light on their varied cell shapes, modes of cell division and extensive signalling and metabolic potential.

Small colony variants of Staphylococcus aureus induce glycolysis and necroptosis in host cells, which impairs trained immunity and host protection from subsequent S. aureus infection.

Single-cell sequencing of flagellated heterotrophic unicellular eukaryotes provides insights into the dynamics of mitochondrial genome evolution.

In this work, Fang et al. analyse the epigenetic landscape of Clostridioides difficile and identify a DNA methyltransferase present across C. difficile strains that is required for optimal sporulation and in vivo colonization and disease.

Viral infection from the basolateral side of intestinal epithelial cells (IECs) is shown to elicit a stronger intrinsic immune response than apical infection, an effect driven by the polarized sorting of Toll-like receptor 3. Experiments in mice and human cells suggest that the cellular polarity program is integral to the ability of IECs to tolerate gut commensals while remaining responsive to invasive pathogens.

This study reports a microscopy-based screen to find microRNAs (miRNAs) that control infection by Salmonella and Shigella, showing they have different requirements. Two miRNAs decrease Shigella actin motility through N-WASP and one miRNA inhibits Salmonella by targeting TGS2, a regulator of phagolysosomal trafficking.

The hierarchical consumption of carbon substrates by Escherichia coli is regulated by carbon-uptake flux rather than by the identity of the substrates, in a process controlled by cAMP–Crp signalling and fructose 1,6-bisphosphate.

The structure of the FlaG–FlaF complexes from Sulfolobus acidocaldarius, combined with mutational and biochemical studies, suggests that these proteins form a heterotetrameric complex in which FlaF regulates the filamentation of FlaG and anchoring of the archaellum to the S-layer, thereby modulating motility.