Glycolytic Staphylococcus aureus generate lactate that targets specific histone deacetylases to stimulate the production of IL-10 and enable biofilm formation.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Many pathogenic fungi depend on the development of specialized infection structures called appressoria to invade their hosts and cause disease. Impairing the function of fungal infection structures therefore provides a potential means by which diseases could be prevented. In spite of this extraordinary potential, however, relatively few anti-penetrant drugs have been developed to control fungal diseases

Cellular adhesion mediates many important plant–microbe interactions. In the devastating blast fungus Magnaporthe oryzae1, powerful glycoprotein-rich mucilage adhesives2 cement melanized and pressurized dome-shaped infection cells—appressoria—to host rice leaf surfaces. Enormous internal turgor pressure is directed onto a penetration peg emerging from the unmelanized, thin-walled pore at the appressorial

The bacterial flagellum is the prototypical protein nanomachine and comprises a rotating helical propeller attached to a membrane-embedded motor complex. The motor consists of a central rotor surrounded by stator units that couple ion flow across the cytoplasmic membrane to generate torque. Here, we present the structures of the stator complexes from Clostridium sporogenes, Bacillus subtilis and Vibrio

Antibody-based drugs and vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are being expedited through preclinical and clinical development. Data from the study of SARS-CoV and other respiratory viruses suggest that anti-SARS-CoV-2 antibodies could exacerbate COVID-19 through antibody-dependent enhancement (ADE). Previous respiratory syncytial virus and dengue virus vaccine

Varicella-zoster virus (VZV) is a medically important human herpesvirus that causes chickenpox and shingles, but its cell-associated nature has hindered structure studies. Here we report the cryo-electron microscopy structures of purified VZV A-capsid and C-capsid, as well as of the DNA-containing capsid inside the virion. Atomic models derived from these structures show that, despite enclosing a genome

Anthrax lethal toxin (LT), produced by Bacillus anthracis, comprises a receptor-binding moiety, protective antigen and the lethal factor (LF) protease1,2. Although LF is known to cleave mitogen-activated protein kinase kinases (MEKs/MKKs) and some variants of the NLRP1 inflammasome sensor, targeting of these pathways does not explain the lethality of anthrax toxin1,2. Here we report that the regulatory

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Fluoxazolevir is an aryloxazole-based entry inhibitor of hepatitis C virus (HCV). We show that fluoxazolevir inhibits fusion of HCV with hepatic cells by binding HCV envelope protein 1 to prevent fusion. Nine of ten fluoxazolevir resistance-associated substitutions are in envelope protein 1, and four are in a putative fusion peptide. Pharmacokinetic studies in mice, rats and dogs revealed that fluoxazolevir

Meta-analysis of four human cohort studies reveals specific keystone bacteria associated with gut microbiome recovery after antibiotic exposure.

The dogma that conversion of the RNA genome of HIV into DNA occurs in the cytoplasm before nuclear entry is challenged using nuclear pore blockade experiments.

Candida auris is among the most important emerging fungal pathogens, yet mechanistic insights into its immune recognition and control are lacking. Here, we integrate transcriptional and functional immune-cell profiling to uncover innate defence mechanisms against C. auris. C. auris induces a specific transcriptome in human mononuclear cells, a stronger cytokine response compared with Candida albicans

There is growing evidence that phages with unusually large genomes are common across various microbiomes, but little is known about their genetic inventories or potential ecosystem impacts. In the present study, we reconstructed large phage genomes from freshwater lakes known to contain bacteria that oxidize methane. Of manually curated genomes, 22 (18 are complete), ranging from 159 kilobase (kb)

Cells infected by influenza virus mount a large-scale antiviral response and most cells ultimately initiate cell-death pathways in an attempt to suppress viral replication. We performed a CRISPR–Cas9-knockout selection designed to identify host factors required for replication after viral entry. We identified a large class of presumptive antiviral factors that unexpectedly act as important proviral

Cyclic-oligonucleotide-based anti-phage signalling systems (CBASS) are a family of defence systems against bacteriophages (hereafter phages) that share ancestry with the cGAS–STING innate immune pathway in animals. CBASS systems are composed of an oligonucleotide cyclase, which generates signalling cyclic oligonucleotides in response to phage infection, and an effector that is activated by the cyclic

Bacteria respond to changes in their environment with specific transcriptional programmes, but even within genetically identical populations these programmes are not homogenously expressed1. Such transcriptional heterogeneity between individual bacteria allows genetically clonal communities to develop a complex array of phenotypes1, examples of which include persisters that resist antibiotic treatment

Sensing of microbes activates the innate immune system, depending on functional mitochondria. However, pathogenic bacteria inhibit mitochondrial activity by delivering toxins via outer membrane vesicles (OMVs). How macrophages respond to pathogenic microbes that target mitochondria remains unclear. Here, we show that macrophages exposed to OMVs from Neisseria gonorrhoeae, uropathogenic Escherichia

Dissimilatory sulfate reduction (DSR)—an important reaction in the biogeochemical sulfur cycle—has been dated to the Palaeoarchaean using geological evidence, but its evolutionary history is poorly understood. Several lineages of bacteria carry out DSR, but in archaea only Archaeoglobus, which acquired DSR genes from bacteria, has been proven to catalyse this reaction. We investigated substantial rates

The IncC family of broad-host-range plasmids enables the spread of antibiotic resistance genes among human enteric pathogens1,2,3. Although aspects of IncC plasmid conjugation have been well studied4,5,6,7,8,9, many roles of conjugation genes have been assigned based solely on sequence similarity. We applied hypersaturated transposon mutagenesis and transposon-directed insertion-site sequencing to

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Cells can be programmed to monitor and react to their environment using genetic circuits. Design automation software maps a desired circuit function to a DNA sequence, a process that requires units of gene regulation (gates) that are simple to connect and behave predictably. This poses a challenge for eukaryotes due to their complex mechanisms of transcription and translation. To this end, we have

Obligate intracellular bacteria such as Chlamydia trachomatis undergo a complex developmental cycle between infectious, non-replicative elementary-body and non-infectious, replicative reticulate-body forms. Elementary bodies transform to reticulate bodies shortly after entering a host cell, a crucial process in infection, initiating chlamydial replication. As Chlamydia fail to replicate outside the

There are outstanding evolutionary questions on the recent emergence of human coronavirus SARS-CoV-2 including the role of reservoir species, the role of recombination and its time of divergence from animal viruses. We find that the sarbecoviruses—the viral subgenus containing SARS-CoV and SARS-CoV-2—undergo frequent recombination and exhibit spatially structured genetic diversity on a regional scale

As the first discovered human cancer virus, Epstein–Barr virus (EBV) causes Burkitt’s lymphoma and nasopharyngeal carcinoma. Isolating virions for determining high-resolution structures has been hindered by latency—a hallmark of EBV infection—and atomic structures are thus available only for recombinantly expressed EBV proteins. In the present study, by symmetry relaxation and subparticle reconstruction

Cell identity in eukaryotes is controlled by transcriptional regulatory networks that define cell-type-specific gene expression. In the opportunistic fungal pathogen Candida albicans, transcriptional regulatory networks regulate epigenetic switching between two alternative cell states, ‘white’ and ‘opaque’, that exhibit distinct host interactions. In the present study, we reveal that the transcription

Escherichia coli is an important model organism in microbiology and a prominent member of the human microbiota1. Environmental isolates readily colonize the gastrointestinal tract of humans and other animals, and they can serve diverse probiotic, commensal and pathogenic roles in the host2,3,4. Although certain strains have been associated with the severity of inflammatory bowel disease (IBD)2,5, the

A virus has been found inserted into the genome of the most abundant bacteria in the oceans. Even though the virus can kill its host, the genes carried by the prophage may help these bacteria flourish around the world.

A dual-mechanism compound with antibacterial activity that targets both folate metabolism and membrane integrity, with a favourable resistance profile in vitro, is identified by screening a small molecule library.

Marine bacteria that produce an enormous panoply of glycan-degrading enzymes are identified as having a role in releasing fixed carbon present in glycan-rich cell walls of brown algae.

We reflect on why we need the World Health Organization now more than ever.

Iron-scavenging molecules called siderophores that are produced by the native microbial residents of plant roots fend off plant pathogens such as Ralstonia solanacearum.

Zoonotic coronaviruses (CoVs) are substantial threats to global health, as exemplified by the emergence of two severe acute respiratory syndrome CoVs (SARS-CoV and SARS-CoV-2) and Middle East respiratory syndrome CoV (MERS-CoV) within two decades1,2,3. Host immune responses to CoVs are complex and regulated in part through antiviral interferons. However, interferon-stimulated gene products that inhibit

RNA viruses in aquatic environments remain poorly studied. Here, we analysed the RNA virome from approximately 10 l water from Yangshan Deep-Water Harbour near the Yangtze River estuary in China and identified more than 4,500 distinct RNA viruses, doubling the previously known set of viruses. Phylogenomic analysis identified several major lineages, roughly, at the taxonomic ranks of class, order and

To avoid innate sensing and immune control, human immunodeficiency virus type 1 (HIV-1) has to prevent the accumulation of viral complementary DNA species. Here, we show that the late HIV-1 accessory protein Vpu hijacks DNA repair mechanisms to promote degradation of nuclear viral cDNA in cells that are already productively infected. Vpu achieves this by interacting with RanBP2–RanGAP1*SUMO1–Ubc9 SUMO

Eukaryotic cells, when exposed to environmental or internal stress, activate the integrated stress response (ISR) to restore homeostasis and promote cell survival. Specific stress stimuli prompt dedicated stress kinases to phosphorylate eukaryotic initiation factor 2 (eIF2). Phosphorylated eIF2 (p-eIF2) in turn sequesters the eIF2-specific guanine exchange factor eIF2B to block eIF2 recycling, thereby

The ongoing pandemic spread of a new human coronavirus, SARS-CoV-2, which is associated with severe pneumonia/disease (COVID-19), has resulted in the generation of tens of thousands of virus genome sequences. The rate of genome generation is unprecedented, yet there is currently no coherent nor accepted scheme for naming the expanding phylogenetic diversity of SARS-CoV-2. Here, we present a rational

The kinetochore is a macromolecular structure that assembles on the centromeres of chromosomes and provides the major attachment point for spindle microtubules during mitosis. In Trypanosoma brucei, the proteins that make up the kinetochore are highly divergent; the inner kinetochore comprises at least 20 distinct and essential proteins (KKT1–20) that include four protein kinases—CLK1 (also known as

Paramyxoviruses such as human parainfluenza virus type-3 (HPIV3) and measles virus (MeV) are a substantial health threat. In a high-throughput screen for inhibitors of HPIV3 (a major cause of acute respiratory infection), we identified GHP-88309—a non-nucleoside inhibitor of viral polymerase activity that possesses unusual broad-spectrum activity against diverse paramyxoviruses including respiroviruses

Viruses promote infection by hijacking the ubiquitin machinery of the host to counteract or redirect cellular processes. Adenovirus encodes two early proteins, E1B55K and E4orf6, that together co-opt a cellular ubiquitin ligase complex to overcome host defences and promote virus production. Adenovirus mutants lacking E1B55K or E4orf6 display defects in viral RNA processing and protein production, but

Staphylococcus aureus is a leading cause of biofilm-associated prosthetic joint infection (PJI), resulting in considerable disability and prolonged treatment. It is known that host leukocyte IL-10 production is required for S. aureus biofilm persistence in PJI. An S. aureus bursa aurealis Tn library consisting of 1,952 non-essential genes was screened for mutants that failed to induce IL-10 in myeloid-derived

The recent spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exemplifies the critical need for accurate and rapid diagnostic assays to prompt clinical and public health interventions. Currently, several quantitative reverse transcription–PCR (RT–qPCR) assays are being used by clinical, research and public health laboratories. However, it is currently unclear whether results from

Infection with a single influenza A virus (IAV) is only rarely sufficient to initiate productive infection. Instead, multiple viral genomes are often required in a given cell. Here, we show that the reliance of IAV on multiple infection can form an important species barrier. Namely, we find that avian H9N2 viruses representative of those circulating widely at the poultry–human interface exhibit acute

A variety of cell surface structures dictate interactions between bacteria and their environment, including their viruses (bacteriophages). Members of the human gut Bacteroidetes characteristically produce several phase-variable capsular polysaccharides (CPSs), but their contributions to bacteriophage interactions are unknown. To begin to understand how CPSs have an impact on Bacteroides–phage interactions

Efforts to improve representation of Black communities in Nature Microbiology start now.

Cooperative behaviour enables populations of yeast cells to survive high temperatures.

Some cytosolic bacteria deform the plasma membrane to spread from cell to cell. Secretion of 25-hydroxy-cholesterol by macrophages has emerged as a protective response that depletes the cholesterol pool used by these bacteria to disseminate through epithelia.

Monkeypox, a zoonotic disease that is marked in humans by a smallpox-like rash, may present as a rash-less respiratory disease in wild chimpanzees.

Recent population-based1,2,3,4 and clinical studies5 have identified a range of factors associated with human gut microbiome variation. Murine quantitative trait loci6, human twin studies7 and microbiome genome-wide association studies1,3,8,9,10,11,12 have provided evidence for genetic contributions to microbiome composition. Despite this, there is still poor overlap in genetic association across human

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Quiescence is a hallmark of CD4+ T cells latently infected with human immunodeficiency virus 1 (HIV-1). While reversing this quiescence is an effective approach to reactivate latent HIV from T cells in culture, it can cause deleterious cytokine dysregulation in patients. As a key regulator of T-cell quiescence, FOXO1 promotes latency and suppresses productive HIV infection. We report that, in resting

Cell-to-cell communication by exosomes controls normal and pathogenic processes1,2. Viruses can spread in exosomes and thereby avoid immune recognition3. While biogenesis, binding and uptake of exosomes are well characterized4,5, delivery of exosome cargo into the cytoplasm is poorly understood3. We report that the phosphatidylserine receptor HAVCR1 (refs. 6,7) and the cholesterol transporter NPC1

The interplay between host and pathogen relies heavily on rapid protein synthesis and accurate protein targeting to ensure pathogen destruction. To gain insight into this dynamic interface, we combined Click chemistry with pulsed stable isotope labelling of amino acids in cell culture to quantify the host proteome response during macrophage infection with the intracellular bacterial pathogen Salmonella

The assembly of single-amplified genomes (SAGs) and metagenome-assembled genomes (MAGs) has led to a surge in genome-based discoveries of members affiliated with Archaea and Bacteria, bringing with it a need to develop guidelines for nomenclature of uncultivated microorganisms. The International Code of Nomenclature of Prokaryotes (ICNP) only recognizes cultures as ‘type material’, thereby preventing

Industry screens of large chemical libraries have traditionally relied on rich media to ensure rapid bacterial growth in high-throughput testing. We used eukaryotic, nutrient-limited growth media in a compound screen that unmasked a previously unknown hyperactivity of the old antibiotic, rifabutin (RBT), against highly resistant Acinetobacter baumannii. In nutrient-limited, but not rich, media, RBT

Retroviral infection involves the reverse transcription of the viral RNA genome into DNA, which is subsequently integrated into the host cell genome. Human immunodeficiency virus type 1 (HIV-1) and other lentiviruses mediate the infection of non-dividing cells through the ability of the capsid protein1 to engage the cellular nuclear import pathways of the target cell and mediate their nuclear translocation

Type I restriction–modification (R–M) systems are widespread in prokaryotic genomes and provide robust protection against foreign DNA. They are multisubunit enzymes with methyltransferase, endonuclease and translocase activities. Despite extensive studies over the past five decades, little is known about the molecular mechanisms of these sophisticated machines. Here, we report the cryo-electron microscopy

Protease-enabled strand exchange to mediate assembly of type V pilus is confirmed using a combination of cryogenic electron microscopy and X-ray crystal structures.

Earthy-smelling volatiles produced by sporulating Streptomyces attract soil arthropods that eat the bacteria and spread ‘hitch-hiking’ spores.