Journal: Nature Microbiology

Abbreviation

Nat Microbiol

Publisher

Nature

Journal Volumes

ISSN

2058-5276

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2016 - 2019282020 - 202551
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Publications1 - 10 of 79
  • Longevity of major coenzymes allows minimal de novo synthesis in microorganisms
    Item type: Journal Article
    Hartl, Johannes; Kiefer, Patrick; Meyer, Fabian; et al. (2017)
    Nature Microbiology
  • Identification and structure of an extracellular contractile injection system from the marine bacterium Algoriphagus machipongonensis
    Item type: Journal Article
    Xu, Jingwei; Ericson, Charles F.; Lien, Yun-Wei; et al. (2022)
    Nature Microbiology
    Contractile injection systems (CISs) are phage tail-like nanomachines, mediating bacterial cell–cell interactions as either type VI secretion systems (T6SSs) or extracellular CISs (eCISs). Bioinformatic studies uncovered a phylogenetic group of hundreds of putative CIS gene clusters that are highly diverse and widespread; however, only four systems have been characterized. Here we studied a putative CIS gene cluster in the marine bacterium Algoriphagus machipongonensis. Using an integrative approach, we show that the system is compatible with an eCIS mode of action. Our cryo-electron microscopy structure revealed several features that differ from those seen in other CISs: a ‘cap adaptor’ located at the distal end, a ‘plug’ exposed to the tube lumen, and a ‘cage’ formed by massive extensions of the baseplate. These elements are conserved in other CISs, and our genetic tools identified that they are required for assembly, cargo loading and function. Furthermore, our atomic model highlights specific evolutionary hotspots and will serve as a framework for understanding and re−engineering CISs.
  • Stressed Serratia curb CRISPR
    Item type: Other Journal Item
    Christen, Beat (2021)
    Nature Microbiology
    Bacteria use CRISPR-Cas systems as adaptive defence weapons against attacking phages. A new study shows that under severe stress conditions, Serratia turn off their CRISPR immune system to increase the uptake of potentially beneficial plasmids.
  • Transportin-1 binds to the HIV-1 capsid via a nuclear localization signal and triggers uncoating
    Item type: Journal Article
    Fernandez, Juliette; Machado, Anthony K.; Lyonnais, Sébastien; et al. (2019)
    Nature Microbiology
    The initial steps of HIV replication in host cells prime the virus for passage through the nuclear pore and drive the establishment of a productive and irreparable infection. The timely release of the viral genome from the capsid—referred to as uncoating—is emerging as a critical parameter for nuclear import, but the triggers and mechanisms that orchestrate these steps are unknown. Here, we identify β-karyopherin Transportin-1 (TRN-1) as a cellular co-factor of HIV-1 infection, which binds to incoming capsids, triggers their uncoating and promotes viral nuclear import. Depletion of TRN-1, which we characterized by mass spectrometry, significantly reduced the early steps of HIV-1 infection in target cells, including primary CD4+ T cells. TRN-1 bound directly to capsid nanotubes and induced dramatic structural damage, indicating that TRN-1 is necessary and sufficient for uncoating in vitro. Glycine 89 on the capsid protein, which is positioned within a nuclear localization signal in the cyclophilin A-binding loop, is critical for engaging the hydrophobic pocket of TRN-1 at position W730. In addition, TRN-1 promotes the efficient nuclear import of both viral DNA and capsid protein. Our study suggests that TRN-1 mediates the timely release of the HIV-1 genome from the capsid protein shell and efficient viral nuclear import.
  • Early detection and surveillance of SARS-CoV-2 genomic variants in wastewater using COJAC
    Item type: Journal Article
    Jahn, Katharina; Dreifuss, David; Topolsky, Ivan; et al. (2022)
    Nature Microbiology
    The continuing emergence of SARS-CoV-2 variants of concern and variants of interest emphasizes the need for early detection and epidemiological surveillance of novel variants. We used genomic sequencing of 122 wastewater samples from three locations in Switzerland to monitor the local spread of B.1.1.7 (Alpha), B.1.351 (Beta) and P.1 (Gamma) variants of SARS-CoV-2 at a population level. We devised a bioinformatics method named COJAC (Co-Occurrence adJusted Analysis and Calling) that uses read pairs carrying multiple variant-specific signature mutations as a robust indicator of low-frequency variants. Application of COJAC revealed that a local outbreak of the Alpha variant in two Swiss cities was observable in wastewater up to 13 d before being first reported in clinical samples. We further confirmed the ability of COJAC to detect emerging variants early for the Delta variant by analysing an additional 1,339 wastewater samples. While sequencing data of single wastewater samples provide limited precision for the quantification of relative prevalence of a variant, we show that replicate and close-meshed longitudinal sequencing allow for robust estimation not only of the local prevalence but also of the transmission fitness advantage of any variant. We conclude that genomic sequencing and our computational analysis can provide population-level estimates of prevalence and fitness of emerging variants from wastewater samples earlier and on the basis of substantially fewer samples than from clinical samples. Our framework is being routinely used in large national projects in Switzerland and the UK.
  • Systematic analysis of drug combinations against Gram-positive bacteria
    Item type: Journal Article
    Cacace, Elisabetta; Kim, Vladislav; Varik, Vallo; et al. (2023)
    Nature Microbiology
    Drug combinations can expand options for antibacterial therapies but have not been systematically tested in Gram-positive species. We profiled similar to 8,000 combinations of 65 antibacterial drugs against the model species Bacillus subtilis and two prominent pathogens, Staphylococcus aureus and Streptococcus pneumoniae. Thereby, we recapitulated previously known drug interactions, but also identified ten times more novel interactions in the pathogen S. aureus, including 150 synergies. We showed that two synergies were equally effective against multidrug-resistant S. aureus clinical isolates in vitro and in vivo. Interactions were largely species-specific and synergies were distinct from those of Gram-negative species, owing to cell surface and drug uptake differences. We also tested 2,728 combinations of 44 commonly prescribed non-antibiotic drugs with 62 drugs with antibacterial activity against S. aureus and identified numerous antagonisms that might compromise the efficacy of antimicrobial therapies. We identified even more synergies and showed that the anti-aggregant ticagrelor synergized with cationic antibiotics by modifying the surface charge of S. aureus. All data can be browsed in an interactive interface (https://apps.embl.de/combact/).
  • Community-led, integrated, reproducible multi-omics with anvi'o
    Item type: Other Journal Item
    Eren, A. Murat; Clayssen, Quentin; et al. (2021)
    Nature Microbiology
    Big data abound in microbiology, but the workflows designed to enable researchers to interpret data can constrain the biological questions that can be asked. Five years after anvi'o was first published, this community-led multi-omics platform is maturing into an open software ecosystem that reduces constraints in 'omics data analyses.
  • The plant NADPH oxidase RBOHD is required for microbiota homeostasis in leaves
    Item type: Journal Article
    Pfeilmeier, Jonas Sebastian; Petti, Gabriella C.; Bortfeld-Miller, Miriam; et al. (2021)
    Nature Microbiology
    The plant microbiota consists of a multitude of microorganisms that can affect plant health and fitness. However, it is currently unclear how the plant shapes its leaf microbiota and what role the plant immune system plays in this process. Here, we evaluated Arabidopsis thaliana mutants with defects in different parts of the immune system for an altered bacterial community assembly using a gnotobiotic system. While higher-order mutants in receptors that recognize microbial features and in defence hormone signalling showed substantial microbial community alterations, the absence of the plant NADPH oxidase RBOHD caused the most pronounced change in the composition of the leaf microbiota. The rbohD knockout resulted in an enrichment of specific bacteria. Among these, we identified Xanthomonas strains as opportunistic pathogens that colonized wild-type plants asymptomatically but caused disease in rbohD knockout plants. Strain dropout experiments revealed that the lack of RBOHD unlocks the pathogenicity of individual microbiota members driving dysbiosis in rbohD knockout plants. For full protection, healthy plants require both a functional immune system and a microbial community. Our results show that the NADPH oxidase RBOHD is essential for microbiota homeostasis and emphasizes the importance of the plant immune system in controlling the leaf microbiota.
  • Pervasive transmission of a carbapenem resistance plasmid in the gut microbiota of hospitalized patients
    Item type: Journal Article
    Leon-Sampedro, Ricardo; DelaFuente, Javier; Díaz-Agero, Cristina; et al. (2021)
    Nature Microbiology
    Infections caused by carbapenemase-producing enterobacteria (CPE) are a major concern in clinical settings worldwide. Two fundamentally different processes shape the epidemiology of CPE in hospitals: the dissemination of CPE clones from patient to patient (between-patient transfer), and the transfer of carbapenemase-encoding plasmids between enterobacteria in the gut microbiota of individual patients (within-patient transfer). The relative contribution of each process to the overall dissemination of carbapenem resistance in hospitals remains poorly understood. Here, we used mechanistic models combining epidemiological data from more than 9,000 patients with whole genome sequence information from 250 enterobacteria clones to characterize the dissemination routes of a pOXA-48-like carbapenemase-encoding plasmid in a hospital setting over a 2-yr period. Our results revealed frequent between-patient transmission of high-risk pOXA-48-carrying clones, mostly of Klebsiella pneumoniae and sporadically Escherichia coli. The results also identified pOXA-48 dissemination hotspots within the hospital, such as specific wards and individual rooms within wards. Using high-resolution plasmid sequence analysis, we uncovered the pervasive within-patient transfer of pOXA-48, suggesting that horizontal plasmid transfer occurs in the gut of virtually every colonized patient. The complex and multifaceted epidemiological scenario exposed by this study provides insights for the development of intervention strategies to control the in-hospital spread of CPE.
  • Non-canonical start codons confer context-dependent advantages in carbohydrate utilization for commensal E. coli in the murine gut
    Item type: Journal Article
    Cherrak, Yassine; Salazar, Miguel Angel; Näpflin, Nicolas; et al. (2024)
    Nature Microbiology
    Resource competition is a driver of gut microbiota composition. Bacteria can outcompete metabolically similar rivals through the limitation of shared growth-fuelling nutrients. The mechanisms underlying this remain unclear for bacteria with identical sets of metabolic genes. Here we analysed the lactose utilization operon in the murine commensal Escherichia coli 8178. Using in vitro and in vivo approaches, we showed that translation of the lactose utilization repressor gene lacI from its native non-canonical GTG start codon increases the basal expression of the lactose utilization cluster, enhancing adaptation to lactose consumption. Consequently, a strain carrying the wild type lacI GTG start codon outperformed the lacI ATG start codon mutant in the mouse intestine. This advantage was attenuated upon limiting host lactose intake through diet shift or altering the mutant frequency, emphasizing the context-dependent efect of a single nucleotide change on the bacterial ftness of a common member of the gut microbiota. Coupled with a genomic analysis highlighting the selection of non-ATG start codons in sugar utilization regulator genes across the Enterobacteriaceae family, our data exposed an unsuspected function of non-canonical start codons in metabolic competition.
Publications1 - 10 of 79