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Compensatory evolution in NusG improves fitness of drug-resistant M. tuberculosis
In Mycobacterium tuberculosis, the fitness cost of rifampicin resistance is partially due to excessive RNA polymerase pausing and is rescued by mutations in the pro-pausing transcription factor NusG.
- Kathryn A. Eckartt
- , Madeleine Delbeau
- & Jeremy M. Rock
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Dopamine receptor D2 confers colonization resistance via microbial metabolites
In a mouse model of enteric pathogen infection, tryptophan metabolites protect against infection via activation of dopamine receptor D2 and regulation of actin cytoskeletal organization in intestinal epithelial cells.
- Samantha A. Scott
- , Jingjing Fu
- & Pamela V. Chang
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Clostridioides difficile ferrosome organelles combat nutritional immunity
Ferrosome organelles produced by Clostridioides difficile are required to support colonization of the inflamed gut, highlighting the potential of targeting ferrosome formation as an antimicrobial strategy against this important pathogen.
- Hualiang Pi
- , Rong Sun
- & Eric P. Skaar
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C. difficile intoxicates neurons and pericytes to drive neurogenic inflammation
The molecular mechanism underlying the severe neurogenic inflammation induced by Clostridioides difficile is presented, providing a therapeutic target for treating this infection.
- John Manion
- , Melissa A. Musser
- & Min Dong
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Article |
Structure of an endogenous mycobacterial MCE lipid transporter
Proteins of the Mycobacterium smegmatis Mce1 system assemble to form an elongated ABC transporter complex that is long enough to span the impermeable mycobacterial cell envelope.
- James Chen
- , Alice Fruhauf
- & Damian C. Ekiert
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Article
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A Pseudomonas aeruginosa small RNA regulates chronic and acute infection
A study examining bacterial gene expression in human-derived samples identifies a gene encoding a small RNA and describes how it orchestrates the transition between chronic and acute infection in Pseudomonas aeruginosa.
- Pengbo Cao
- , Derek Fleming
- & Marvin Whiteley
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Spike and nsp6 are key determinants of SARS-CoV-2 Omicron BA.1 attenuation
Comparisons of a chimeric recombinant version of SARS-CoV-2, the ancestral SARS-CoV-2 strain and an Omicron isolate show that the attenuated virulence of Omicron is caused by mutations in both the spike protein and nsp6.
- Da-Yuan Chen
- , Chue Vin Chin
- & Mohsan Saeed
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Article
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HIV silencing and cell survival signatures in infected T cell reservoirs
HIV-infected memory CD4 T cells under antiretroviral therapy are a distinctive population of cells with transcriptomic patterns that favour HIV silencing, cell survival and cell proliferation.
- Iain C. Clark
- , Prakriti Mudvari
- & Eli A. Boritz
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Article
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Undecaprenyl phosphate translocases confer conditional microbial fitness
Members of the DUF368-containing and DedA transmembrane protein families have conditional roles in undecaprenyl phosphate translocation in Gram-negative and Gram-positive bacteria and may have a widely conserved function in the biogenesis of microbial cell surface glycopolymers.
- Brandon Sit
- , Veerasak Srisuknimit
- & Matthew K. Waldor
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Article
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Effect of the intratumoral microbiota on spatial and cellular heterogeneity in cancer
Spatial profiling and single-cell RNA sequencing are used to map the spatial distribution of the microbiota within human tumours, revealing how intratumoral microbial communities contribute to tumour heterogeneity and cancer progression.
- Jorge Luis Galeano Niño
- , Hanrui Wu
- & Susan Bullman
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Enterococci enhance Clostridioides difficile pathogenesis
Enterococci enhance the fitness and pathogenesis of Clostridioides difficile in the gut by altering the amino acid composition and providing signals that increase its virulence towards the host.
- Alexander B. Smith
- , Matthew L. Jenior
- & Joseph P. Zackular
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CRISPR screens in Drosophila cells identify Vsg as a Tc toxin receptor
A genome-wide CRISPR–Cas9-mediated knockout screen in Drosophila cells identifies Visgun as a proteinaceous receptor for toxin complex toxins, demonstrating the utility of this approach for investigating insecticidal toxins and pathogens.
- Ying Xu
- , Raghuvir Viswanatha
- & Min Dong
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Article
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Archaic chaperone–usher pili self-secrete into superelastic zigzag springs
The Csu pili of the multidrug-resistant nosocomial pathogen Acinetobacter baumannii assemble into an ultrathin zigzag architecture secured by a clinch mechanism that provides the pilus with high mechanical stability and superelasticity.
- Natalia Pakharukova
- , Henri Malmi
- & Anton V. Zavialov
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Article
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The source of the Black Death in fourteenth-century central Eurasia
- Maria A. Spyrou
- , Lyazzat Musralina
- & Johannes Krause
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Group A Streptococcus induces GSDMA-dependent pyroptosis in keratinocytes
Group A Streptococcus secretes a protease, SpeB, that directly cleaves and activates gasdermin A to induce pyroptosis of infected keratinocytes, demonstrating a role for gasdermin A in immune defence against invasive microorganisms.
- Doris L. LaRock
- , Anders F. Johnson
- & Christopher N. LaRock
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Two defence systems eliminate plasmids from seventh pandemic Vibrio cholerae
Two defence systems are identified in pandemic Vibrio cholerae that act both cooperatively and independently to eliminate invasive plasmids and bacteriophages.
- Milena Jaskólska
- , David W. Adams
- & Melanie Blokesch
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Basis of narrow-spectrum activity of fidaxomicin on Clostridioides difficile
Structural analysis of Clostridioides difficile RNA polymerase in complex with fidaxomicin combined with biochemical, genetic and bioinformatic analyses identifies a key residue that determines fidaxomicin sensitivity.
- Xinyun Cao
- , Hande Boyaci
- & Elizabeth A. Campbell
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Eicosanoid signalling blockade protects middle-aged mice from severe COVID-19
A study reports the isolation and characterization of mouse-adapted SARS-CoV-2, demonstrates asapiprant to protect aged mice from its most severe effects, and identifies the PLA2G2D–PGD2/PTGDR pathway as a therapeutic target.
- Lok-Yin Roy Wong
- , Jian Zheng
- & Stanley Perlman
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Bacterial inhibition of Fas-mediated killing promotes neuroinvasion and persistence
Studies in a mouse model of neurolisteriosis show that the effector protein InlB produced by Listeria monocytogenes protects infected monocytes in the host from T cell-mediated cell death, and thereby increases bacterial neuroinvasion, persistence and transmission.
- Claire Maudet
- , Marouane Kheloufi
- & Marc Lecuit
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Streptococcal pyrogenic exotoxin B cleaves GSDMA and triggers pyroptosis
The Streptococcus pyogenes virulence factor SpeB triggers pyroptosis in keratinocytes by catalysing cleavage of host gasdermin A, a key event triggering the immune response to S. pyogenes infection.
- Wanyan Deng
- , Yang Bai
- & Xing Liu
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Article
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SARS-CoV-2 Omicron virus causes attenuated disease in mice and hamsters
A collaborative study demonstrates that, compared with previous SARS-CoV-2 variants, B.1.1.529 isolates cause less infection and disease in mice and hamsters, in agreement with preliminary data from studies in humans.
- Peter J. Halfmann
- , Shun Iida
- & Yoshihiro Kawaoka
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Shigella evades pyroptosis by arginine ADP-riboxanation of caspase-11
This study reports the identification of a new post-translational modification, termed ADP riboxanation, which is mediated by the Shigella effector OspC3 and inactivates the cytosolic LPS sensing pathway of caspase-4 and caspase-11.
- Zilin Li
- , Wang Liu
- & Feng Shao
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Article
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Leprosy in wild chimpanzees
Monitoring of western chimpanzee populations in Guinea-Bissau and Côte d’Ivoire reveals the presence of rare and different genotypes of Mycobacterium leprae, suggesting greater circulation in wild animals than previously thought.
- Kimberley J. Hockings
- , Benjamin Mubemba
- & Fabian H. Leendertz
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Molecular basis for DarT ADP-ribosylation of a DNA base
Structural and mechanistic data of the ADP-ribosyltransferase DarT demonstrate the role of ADP-ribosylation of DNA by this enzyme in generating toxicity and regulating cellular signalling processes in bacteria.
- Marion Schuller
- , Rachel E. Butler
- & Ivan Ahel
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Review Article |
Unconventional viral gene expression mechanisms as therapeutic targets
This Review outlines the gene and protein expression strategies used by viruses to expand the efficiency of their coding and regulatory sequences, and the implications of these mechanisms for developing antiviral agents.
- Jessica Sook Yuin Ho
- , Zeyu Zhu
- & Ivan Marazzi
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C. difficile exploits a host metabolite produced during toxin-mediated disease
RNA-sequencing experiments determine that sorbitol, a metabolite produced by the host enzyme aldose reductase, is exploited by Clostridium difficile in its adaptation to inflammatory conditions in the gut.
- Kali M. Pruss
- & Justin L. Sonnenburg
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Loss of furin cleavage site attenuates SARS-CoV-2 pathogenesis
Experimental deletion of the furin cleavage site of the SARS-CoV-2 spike protein highlights an important role for this site in infection and the need to consider this site when evaluating the neutralization activities of antibodies.
- Bryan A. Johnson
- , Xuping Xie
- & Vineet D. Menachery
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The ABC exporter IrtAB imports and reduces mycobacterial siderophores
The mycobacterial ABC transporter IrtAB functions as a siderophore importer despite exhibiting an exporter fold in its structure, and contains a siderophore interaction domain capable of siderophore reduction and iron release inside the cell.
- Fabian M. Arnold
- , Miriam S. Weber
- & Markus A. Seeger
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Mutational signature in colorectal cancer caused by genotoxic pks+ E. coli
Organoids derived from human intestinal cells that are co-cultured with bacteria carrying the genotoxic pks+ island develop a distinct mutational signature associated with colorectal cancer.
- Cayetano Pleguezuelos-Manzano
- , Jens Puschhof
- & Hans Clevers
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Article
| Open Access
A pneumonia outbreak associated with a new coronavirus of probable bat origin
Characterization of full-length genome sequences from patients infected with a new coronavirus (2019-nCoV) shows that the sequences are nearly identical and indicates that the virus is related to a bat coronavirus.
- Peng Zhou
- , Xing-Lou Yang
- & Zheng-Li Shi
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Host-mediated ubiquitination of a mycobacterial protein suppresses immunity
Mycobacterium tuberculosis suppresses the production of inflammatory cytokines by host cells through the host-mediated ubiquitination of a mycobacterial protein, enhancing the interaction of a host signalling inhibitor with another signalling molecule.
- Lin Wang
- , Juehui Wu
- & Baoxue Ge
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Letter |
FHL1 is a major host factor for chikungunya virus infection
FHL1 is a key factor expressed by humans and mice that is required for chikungunya virus infection and is therefore a promising target for the development of therapies against chikungunya virus.
- Laurent Meertens
- , Mohamed Lamine Hafirassou
- & Ali Amara
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FPR1 is the plague receptor on host immune cells
The receptor FPR1 on human immune cells interacts with Yersinia pestis, mutations in this receptor provide resistance against plague in humans and Fpr1 deficiency enhances survival in mice.
- Patrick Osei-Owusu
- , Thomas M. Charlton
- & Olaf Schneewind
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Letter |
Stunted microbiota and opportunistic pathogen colonization in caesarean-section birth
Delivery via caesarean section, maternal antibiotic prophylaxis and colonization by opportunistic pathogens associated with the hospital environment affect the composition of the gut microbiota of children from birth until infancy.
- Yan Shao
- , Samuel C. Forster
- & Trevor D. Lawley
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Letter |
Cholera toxin promotes pathogen acquisition of host-derived nutrients
Cholera toxin selectively promotes the growth of Vibrio cholerae through the acquisition of nutrients, including haem and fatty acids, from the host gut.
- Fabian Rivera-Chávez
- & John J. Mekalanos
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Letter |
Inhibition of bacterial ubiquitin ligases by SidJ–calmodulin catalysed glutamylation
In cells infected with Legionella pneumophila, the pseudo kinase SidJ is activated upon forming a complex with human calmodulin and catalyses glutamylation of SidE ubiquitin ligases, which abolishes the activity of these enzymes.
- Sagar Bhogaraju
- , Florian Bonn
- & Ivan Dikic
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Letter |
Regulation of phosphoribosyl ubiquitination by a calmodulin-dependent glutamylase
In Legionella pneumophila, the effector SidJ induces the covalent attachment of glutamate moieties to SdeA in a calmodulin-dependent manner, inhibiting SidE-mediated ubiquitination and regulating pathogenicity.
- Ninghai Gan
- , Xiangkai Zhen
- & Zhao-Qing Luo
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Letter |
Structural basis of unidirectional export of lipopolysaccharide to the cell surface
Crystal structures of a five-protein complex comprising the inner-membrane components of the bacterial lipopolysaccharide transporter provide insight into the mechanism of extraction of lipopolysaccharide from the inner membrane and its transport to the outer membrane.
- Tristan W. Owens
- , Rebecca J. Taylor
- & Daniel Kahne
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Letter |
A NIK–SIX signalling axis controls inflammation by targeted silencing of non-canonical NF-κB
Non-canonical NF-κB is regulated by a negative feedback loop involving NIK-mediated activation of SIX1 and SIX2.
- Zixu Liu
- , Katrina B. Mar
- & Neal M. Alto
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Letter |
Methicillin-resistant Staphylococcus aureus alters cell wall glycosylation to evade immunity
Strains of methicillin-resistant Staphylococcus aureus use a prophage-encoded glycosyltransferase to alter the glycosylation of their wall teichoic acid and thereby evade antibody-mediated immune responses.
- David Gerlach
- , Yinglan Guo
- & Andreas Peschel
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Article |
Pathogen elimination by probiotic Bacillus via signalling interference
Lipopeptides secreted by Bacillus bacteria block quorum sensing by Staphylococcus aureus and thereby inhibit the growth of this opportunistic pathogen in the gut, suggesting why people in rural Thailand who are colonized by Bacillus are not also colonized by S. aureus.
- Pipat Piewngam
- , Yue Zheng
- & Michael Otto
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Article |
Tc toxin activation requires unfolding and refolding of a β-propeller
A high-resolution cryo-electron microscopy structure of a complete Tc holotoxin complex reveals the precise mechanism of Tc toxin assembly, gate opening and release of the cytotoxic enzyme into the translocation channel.
- Christos Gatsogiannis
- , Felipe Merino
- & Stefan Raunser
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Letter |
A flavin-based extracellular electron transfer mechanism in diverse Gram-positive bacteria
The Gram-positive Listeria monocytogenes pathogen possesses a distinctive extracellular electron transfer mechanism, which is probably present in numerous ecologically diverse species of the Firmcutes phylum.
- Samuel H. Light
- , Lin Su
- & Daniel A. Portnoy
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Letter |
An orthogonal proteomic survey uncovers novel Zika virus host factors
Integrative analyses identify host proteins that are modulated by Zika virus at multiple levels and provide a comprehensive framework for the understanding of Zika virus-induced changes to cellular pathways.
- Pietro Scaturro
- , Alexey Stukalov
- & Andreas Pichlmair
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Letter |
Insights into catalysis and function of phosphoribosyl-linked serine ubiquitination
Structural and functional investigations demonstrate how bacterial enzymes ubiquitinate host proteins.
- Sissy Kalayil
- , Sagar Bhogaraju
- & Ivan Dikic
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Letter |
Architecture of a channel-forming O-antigen polysaccharide ABC transporter
The crystal structure of a channel-forming O-antigen polysaccharide ABC transporter suggests a novel biopolymer translocation mechanism.
- Yunchen Bi
- , Evan Mann
- & Jochen Zimmer
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Article |
Dietary trehalose enhances virulence of epidemic Clostridium difficile
Two hypervirulent ribotypes of the enteric pathogen Clostridium difficile, RT027 and RT078, have independently acquired unique mechanisms to metabolize low concentrations of the disaccharide trehalose, suggesting a correlation between the emergence of these ribotypes and the widespread adoption of trehalose in the human diet.
- J. Collins
- , C. Robinson
- & R. A. Britton
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Letter |
Persistent anthrax as a major driver of wildlife mortality in a tropical rainforest
An anthrax-causing agent, Bacillus cereus biovar anthracis, is a persistent and widespread cause of death for a broad range of mammalian hosts in a tropical rainforest, with important implications for the conservation of mammals such as chimpanzees.
- Constanze Hoffmann
- , Fee Zimmermann
- & Fabian H. Leendertz
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Letter |
Nutrient sensing modulates malaria parasite virulence
Malaria parasites use a sensing mechanism to moderate their growth in response to the nutrient content of their host.
- Liliana Mancio-Silva
- , Ksenija Slavic
- & Maria M. Mota
A distinct Fusobacterium nucleatum clade dominates the colorectal cancer niche