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Mycobacterium tuberculosis acquires iron by cell-surface sequestration and internalization of human holo-transferrin
Mycobacterium tuberculosis acquires iron from its host by producing iron-binding siderophores and by recruiting host transferrin to the phagosome. Here, Boradia et al. show that the bacterial GAPDH protein binds transferrin and drives the uptake of this host protein into M. tuberculosiscells.
- Vishant Mahendra Boradia
- , Himanshu Malhotra
- & Chaaya Iyengar Raje
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Functional high-throughput screening identifies the miR-15 microRNA family as cellular restriction factors for Salmonella infection
The functional role of microRNAs in the interplay between bacterial pathogens and host cells is not well defined. Here, using an image-based high-throughput screening approach, the authors identify a family of microRNAs that regulates Salmonellainfection and characterize their mechanism of action.
- Claire Maudet
- , Miguel Mano
- & Ana Eulalio
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| Open AccessIdentification of a human neonatal immune-metabolic network associated with bacterial infection
Infection remains a leading cause of morbidity and mortality in neonates worldwide. Here the authors report disproportionate immune stimulatory, co-inhibitory and metabolic pathway responses that specifically mark bacterial infection and can be used to predict sepsis in neonatal patients at the first clinical signs of infection.
- Claire L. Smith
- , Paul Dickinson
- & Peter Ghazal
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Host iron status and iron supplementation mediate susceptibility to erythrocytic stage Plasmodium falciparum
It remains unclear why iron deficiency can protect from malaria infection. Here the authors show that iron-deficient microcytic erythrocytes are less efficiently infected by Plasmodium falciparumparasites and that iron supplementation increases the proportion of young erythrocytes more susceptible to infection.
- Martha A. Clark
- , Morgan M. Goheen
- & Carla Cerami
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An infectious bat-derived chimeric influenza virus harbouring the entry machinery of an influenza A virus
An uncharacterized influenza A-like virus (H17N10) has been detected in bats. Here the authors show that flu viruses containing certain H17N10 genes can infect human cells and mice, but do not exchange genes with other viruses, indicating that H17N10 transmission to humans is not very likely.
- Mindaugas Juozapaitis
- , Étori Aguiar Moreira
- & Martin Schwemmle
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A micro-sterile inflammation array as an adjuvant for influenza vaccines
There is a need of improved adjuvants for influenza vaccines. Here, the authors describe an adjuvant strategy using micro-fractional laser treatment combined with a topical cream containing a TLR 7 ligand that can enhance the immune response to intradermal vaccination with transient, constrained local inflammation.
- Ji Wang
- , Dilip Shah
- & Mei X. Wu
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Isocitrate lyase mediates broad antibiotic tolerance in Mycobacterium tuberculosis
Mycobacterium tuberculosisis intrinsically resistant to most antibiotics. Here, the authors show that the pathogen’s tolerance to three antibiotics, each one targeting a distinct cellular process, is mediated by an antioxidant response that requires the activation of isocitrate lyases.
- Madhumitha Nandakumar
- , Carl Nathan
- & Kyu Y. Rhee
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Glycosphingolipid-functionalized nanoparticles recapitulate CD169-dependent HIV-1 uptake and trafficking in dendritic cells
Ganglioside GM3, a cellular lipid included in the envelope of HIV-1 viral particles, interacts with cellular receptor CD169. Here, the authors develop artificial nanoparticles, consisting of a golden core and a GM3-containing synthetic membrane, that recapitulate the CD169-dependent uptake of viral particles.
- Xinwei Yu
- , Amin Feizpour
- & Björn M. Reinhard
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Interferon controls SUMO availability via the Lin28 and let-7 axis to impede virus replication
Protein modification by small ubiquitin-related modifier (SUMO) proteins is associated with antiviral responses. Here, the authors show that interferons increase the level of expression of SUMO proteins via a let-7 microRNA-controlled mechanism, and this contributes to the antiviral effects of interferons.
- Umut Sahin
- , Omar Ferhi
- & Valérie Lallemand-Breitenbach
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| Open AccessPredicting the risk of avian influenza A H7N9 infection in live-poultry markets across Asia
An avian influenza virus of the H7N9 type, associated with live-poultry markets, has caused two human epidemics in China. Here, the authors develop a statistical model that predicts the risk of H7N9 infection in live-poultry markets across Asia, as a tool for disease surveillance and control.
- Marius Gilbert
- , Nick Golding
- & Hongjie Yu
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Plasticity and redundancy among AMA–RON pairs ensure host cell entry of Toxoplasma parasites
Apicomplexan parasites such as Toxoplasma gondii and Plasmodium form a tight, moving junction with host cells before invading them. Here the authors show that the proteins AMA1 and RON2 of T. gondiicooperate during junction formation and identify additional proteins that have a role in this process.
- Mauld H. Lamarque
- , Magali Roques
- & Maryse Lebrun
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A mutation burst during the acute phase of Helicobacter pylori infection in humans and rhesus macaques
Helicobacter pylori chronically infects humans, and this is associated with high mutation and recombination rates in the bacterium. Here the authors provide evidence that genome evolution in H. pyloriduring acute infection of the host is orders of magnitude faster than any previously determined mutation rates in bacteria.
- Bodo Linz
- , Helen M. Windsor
- & Barry J. Marshall
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Membrane deformation and scission by the HSV-1 nuclear egress complex
Two viral proteins form the nuclear egress complex of herpesviruses, which is essential for the exit of nascent viral capsids from the cell nucleus. Here, the authors use synthetic lipid vesicles to show that the complex can mediate membrane budding in the absence of other cellular factors.
- Janna M. Bigalke
- , Thomas Heuser
- & Ekaterina E. Heldwein
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Targeting Mycobacterium tuberculosis nucleoid-associated protein HU with structure-based inhibitors
Histone-like HU proteins play roles in chromatin architecture and DNA-dependent processes in bacteria. Here, the authors describe the crystal structure of the DNA-binding domain of HU from Mycobacterium tuberculosis, and show that the pathogen’s growth can be inhibited using HU-targeting small molecules.
- Tuhin Bhowmick
- , Soumitra Ghosh
- & Valakunja Nagaraja
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| Open AccessEvidence of natural Wolbachia infections in field populations of Anopheles gambiae
Wolbachia bacteria live within the cells of many insect species, manipulating their hosts’ reproduction and immune responses. Here, the authors show that these microbes also infect wild populations of malaria-spreading Anopheles mosquitoes, supporting a potential use of Wolbachiato limit malaria transmission.
- Francesco Baldini
- , Nicola Segata
- & Flaminia Catteruccia
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Antigen capture and archiving by lymphatic endothelial cells following vaccination or viral infection
Viral antigens can persist within the secondary lymphoid tissues of the host for many weeks after resolution of the infection. Tamburini et al.demonstrate that antigens remaining following viral infection or vaccination can be captured and maintained for extended periods of time by lymphatic endothelial cells.
- Beth A. Tamburini
- , Matthew A. Burchill
- & Ross M. Kedl
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| Open AccessPathogenic potential of interferon αβ in acute influenza infection
Interferon αβ(IFNαβ) is known as a potent anti-viral factor, yet its role in influenza infection remains controversial. Here, the authors show that the IFNαβ response is a critical host factor, which, when excessive, causes strong inflammation and severe disease in a mouse model of acute influenza infection.
- Sophia Davidson
- , Stefania Crotta
- & Andreas Wack
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Emergent properties of the interferon-signalling network may underlie the success of hepatitis C treatment
The standard treatment for hepatitis C virus (HCV) infection, combining interferon (IFN) α and ribavirin, fails in a number of patients. Here, the authors use a mathematical model of the IFN signalling network in the presence of HCV to explain the success or failure of hepatitis C treatment.
- Pranesh Padmanabhan
- , Urtzi Garaigorta
- & Narendra M. Dixit
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| Open AccessA high-coverage shRNA screen identifies TMEM129 as an E3 ligase involved in ER-associated protein degradation
The human cytomegalovirus protein US11 downregulates host immune responses by redirecting HLA class I molecules for endoplasmic reticulum-associated protein degradation. Using a high-coverage genome-wide shRNA screen, the authors identify TMEM129 as an E3 ubiquitin ligase essential for this process.
- Michael L. van de Weijer
- , Michael C. Bassik
- & Robert Jan Lebbink
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Angiotensin II plasma levels are linked to disease severity and predict fatal outcomes in H7N9-infected patients
An avian influenza H7N9 virus causes severe human disease, including acute and often lethal respiratory failure. Here, the authors report that plasma levels of angiotensin II, a regulatory peptide of the renin–angiotensin system, are associated with disease severity and fatal outcome in infected patients.
- Fengming Huang
- , Jing Guo
- & Lanjuan Li
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MicroRNA-302b augments host defense to bacteria by regulating inflammatory responses via feedback to TLR/IRAK4 circuits
Bacterial infection stimulates a powerful inflammatory response that must be regulated to prevent tissue damage. Zhou et al.identify microRNA-302b as a feedback suppressor of inflammatory signalling that alleviates lung injury following Pseudomonas infection by targeting the NF-κB activator IRAK4.
- Xikun Zhou
- , Xuefeng Li
- & Min Wu
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Receptor mimicry by antibody F045–092 facilitates universal binding to the H3 subtype of influenza virus
Influenza A H3 viruses circulate in humans and bind host cells using the haemagglutinin (HA) glycoprotein. Here, Lee et al.perform a structural analysis of antibody F045–092 with broadly neutralizing activity against the H3 subtype and reveal its interaction with the HA receptor binding site.
- Peter S. Lee
- , Nobuko Ohshima
- & Ian A. Wilson
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| Open AccessCell wall precursors are required to organize the chlamydial division septum
Cell division in Chlamydiales remains mysterious as it occurs in the absence of a cytokinetic tubulin and a classical peptidoglycan cell wall. Jacquier et al. show that the actin homologue MreB is recruited to the division site in Waddliaand that this depends on synthesis of the peptidoglycan precursor lipid II.
- Nicolas Jacquier
- , Antonio Frandi
- & Gilbert Greub
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Direct visualization of HIV-enhancing endogenous amyloid fibrils in human semen
Semen-derived peptides can form amyloid fibrils that boost HIV infection in vitro, but the existence of such fibrils in semen remained to be demonstrated. Here, the authors show that human semen contains amyloid fibrils, which can bind HIV particles and increase their infectiveness.
- Shariq M. Usmani
- , Onofrio Zirafi
- & Jan Münch
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FoxP3+ regulatory T cells promote influenza-specific Tfh responses by controlling IL-2 availability
Regulatory T cells (Tregs) are mainly known to suppress effector T cell and B-cell responses. Here, the authors demonstrate that Tregs are able to promote T follicular helper and germinal centre B-cell responses to influenza by sequestering IL-2, the negative regulator of T follicular helper cell differentiation.
- Beatriz León
- , John E. Bradley
- & André Ballesteros-Tato
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| Open AccessDelayed bactericidal response of Mycobacterium tuberculosis to bedaquiline involves remodelling of bacterial metabolism
The delayed onset of bactericidal activity of the anti-tuberculosis antibiotic bedaquiline is puzzling. Here, Koul and colleagues show, using a multi-omics approach, that the drug triggers a metabolic remodelling in Mycobacterium tuberculosisthat enables the pathogen’s transient survival.
- Anil Koul
- , Luc Vranckx
- & Dirk Bald
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Inhibition of miR-146a prevents enterovirus-induced death by restoring the production of type I interferon
Enterovirus 71 (EV71) is one of the causative agents of hand-food-mouth disease and to date, effective vaccines or antivirals against the disease have not been developed. Here, the authors show that blocking miR-146a upregulation induced upon EV71 infection can have a positive effect on the resolution of infection.
- Bing-Ching Ho
- , I-Shing Yu
- & Sung-Liang Yu
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African origin of the malaria parasite Plasmodium vivax
Plasmodium vivax, the leading cause of human malaria in Asia and Latin America, is thought to have an Asian origin. Here, the authors show that wild chimpanzees and gorillas in Africa are infected with parasites that are closely related to P. vivax, indicating an African origin for this species.
- Weimin Liu
- , Yingying Li
- & Paul M. Sharp
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| Open AccessEstimates of the changing age-burden of Plasmodium falciparum malaria disease in sub-Saharan Africa
Reduction in malaria transmission has changed the age pattern of malaria incidence. This study brings insights into the changes in age distributions of clinical malaria across Africa, with importance for improving within-population targeting of malaria control interventions.
- Jamie T. Griffin
- , Neil M. Ferguson
- & Azra C. Ghani
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Fragile X mental retardation protein stimulates ribonucleoprotein assembly of influenza A virus
To successfully replicate and propagate, viruses hijack different components of the host cell machinery. Here, Zhou et al.identify the RNA-binding protein Fragile X mental retardation protein as a host factor involved in influenza A virus replication in host cells.
- Zhuo Zhou
- , Mengmeng Cao
- & Tao Deng
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Structure-based discovery of Middle East respiratory syndrome coronavirus fusion inhibitor
MERS-CoV is a novel human coronavirus that has recently caused outbreaks of respiratory illness with high case fatality rate. Here the authors characterize the membrane fusion apparatus of MERS-CoV and develop a peptide that can inhibit virus fusion and replication in vitro.
- Lu Lu
- , Qi Liu
- & Shibo Jiang
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Dynamic reassortments and genetic heterogeneity of the human-infecting influenza A (H7N9) virus
H7N9 influenza A viruses capable of infecting humans have recently emerged in China. Here, the authors show that these viruses remain genetically diverse, suggesting that they are still in the process of adapting to human hosts.
- Lunbiao Cui
- , Di Liu
- & George F. Gao
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Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection
Antibiotics alter the intestinal microbiota and facilitate colonization of pathogens such as Clostridium difficile. Here, the authors show that antibiotic-induced shifts in the mouse gut microbiome are correlated with changes in levels of certain metabolites that C. difficilecan use for germination and growth.
- Casey M. Theriot
- , Mark J. Koenigsknecht
- & Vincent B. Young
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| Open AccessTRPA1 channels mediate acute neurogenic inflammation and pain produced by bacterial endotoxins
Gram-negative bacterial infections can often cause inflammation and pain. Meseguer et al. show that the inflammation and pain result from the direct activation of nociceptor TRPA1 channels by lipopolysaccharide, a major component of the outer membrane of Gram-negative bacteria.
- Victor Meseguer
- , Yeranddy A. Alpizar
- & Félix Viana
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Indoleamides are active against drug-resistant Mycobacterium tuberculosis
New classes of antitubercular drugs are in constant demand as drug-resistant strains of Mycobacterium tuberculosis become more prevalent. Here, the authors characterize a class of drugs that are active against various M. tuberculosisstrains, including those resistant to currently used antituberculars.
- Shichun Lun
- , Haidan Guo
- & William R. Bishai
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| Open AccessInfluenza A(H7N9) virus gains neuraminidase inhibitor resistance without loss of in vivo virulence or transmissibility
Some clinical isolates of influenza A(H7N9) virus encode a mutation within neuraminidase that could confer resistance to the only class of drugs active against H7N9. Here, the authors show that this mutation does not affect viral replication and pathogenicity while mediating resistance to antivirals in vivo.
- Rong Hai
- , Mirco Schmolke
- & Nicole M. Bouvier
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Real-time influenza forecasts during the 2012–2013 season
Our ability to accurately predict the spread of infectious diseases is still in its infancy. Here, Shamanet al.develop a model framework that produces accurate real-time forecasts of influenza peak timing for over a hundred cities in the USA.
- Jeffrey Shaman
- , Alicia Karspeck
- & Marc Lipsitch
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| Open AccessProtective CD8+ T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation
Induction of protective immunity mediated by CD8+ T cells has been a long sought goal in vaccinology. Here, Ewer et al. report induction of protective efficacy against Plasmodium falciparummalaria in a phase IIa prime-boost vaccine trial where efficacy correlates strongly with induced CD8 T-cell responses.
- Katie J. Ewer
- , Geraldine A. O’Hara
- & Adrian V. S. Hill
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VapC20 of Mycobacterium tuberculosis cleaves the Sarcin–Ricin loop of 23S rRNA
Toxin–antitoxin systems have been implicated in the pathogenicity of Mycobacterium tuberculosis. Here, the authors study the function of the M. tuberculosistoxin VapC20 and show that it can impair protein translation and inhibit bacterial growth by cleaving the Sarcin–Ricin loop of 23S rRNA
- Kristoffer S. Winther
- , Ditlev E. Brodersen
- & Kenn Gerdes
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Mechanism of inhibition of Mycobacterium tuberculosis antigen 85 by ebselen
As drug-resistant strains of Mycobacterium tuberculosis continue to emerge, antitubercular drugs with novel mechanisms of action are in high demand. Here, the authors show that ebselen is an inhibitor of M. tuberculosisantigen 85 and reveal the mechanism of inhibition.
- Lorenza Favrot
- , Anna E. Grzegorzewicz
- & Donald R. Ronning
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Acute emergence and reversion of influenza A virus quasispecies within CD8+ T cell antigenic peptides
Cytotoxic CD8+ T cells provide one level of protection against influenza infection. Here, the authors present evidence, in mice and humans, for the emergence and reversion of influenza A virus escape mutants associated with the immune pressure from cytotoxic CD8+ T lymphocytes.
- Sophie A. Valkenburg
- , Sergio Quiñones-Parra
- & Katherine Kedzierska
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Perpetual expression of PAMPs necessary for optimal immune control and clearance of a persistent pathogen
Pathogen-associated molecular patterns are involved in the initiation of anti-pathogen immunity but their importance for sustaining this response is not established. Here, the authors show that persistent presence of pathogen-associated molecular patterns is required to maintain robust immune responses to pathogens.
- Samarchith P. Kurup
- & Rick L. Tarleton
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Selection on haemagglutinin imposes a bottleneck during mammalian transmission of reassortant H5N1 influenza viruses
Mutations in the haemagglutinin of H5N1 avian influenza viruses confer transmissibility in ferrets. Here, Wilker et al. show that while within host variability is high, transmitted virus diversity is low suggesting a genetic bottleneck acts during transmission, driven by selection on haemagglutinin genes.
- Peter R. Wilker
- , Jorge M. Dinis
- & Thomas C. Friedrich
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Real-time in vivo imaging of invasive- and biomaterial-associated bacterial infections using fluorescently labelled vancomycin
Invasive and biomaterial-associated infections in humans are often difficult to diagnose and treat. Here, the authors demonstrate that real-time in vivodetection and imaging of these bacterial infections can be successfully performed with fluorescently labelled vancomycin.
- Marleen van Oosten
- , Tina Schäfer
- & Gooitzen M. van Dam
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| Open AccessApical membrane antigen 1 mediates apicomplexan parasite attachment but is dispensable for host cell invasion
Plasmodium and Toxoplasma apical membrane antigen 1 (AMA1) is believed to be actively involved in host cell invasion by these parasites. Bargieri et al. now demonstrate that although AMA1 facilitates adhesion, invasion can proceed in the absence of the protein.
- Daniel Y. Bargieri
- , Nicole Andenmatten
- & Robert Ménard
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| Open Accessp53 increases MHC class I expression by upregulating the endoplasmic reticulum aminopeptidase ERAP1
The protein p53 is an important tumour suppressor. Here Wanget al.show that p53 can induce expression of MHC class I on the cell surface by promoting expression of the aminopeptidase ERAP1, and that this mechanism operates in cancer cells as well as those infected with influenza virus.
- Bei Wang
- , Dandan Niu
- & Ee Chee Ren
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Disrupting malaria parasite AMA1–RON2 interaction with a small molecule prevents erythrocyte invasion
Invasion of host erythrocytes is an essential step in the life cycle of P. falciparum. Srinivasan et al.demonstrate that small-molecule inhibitors can block the entry of the parasite into erythrocytes, highlighting the potential of invasion inhibitors as antimalarials.
- Prakash Srinivasan
- , Adam Yasgar
- & Louis H. Miller
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| Open AccessBacterial colonization dampens influenza-mediated acute lung injury via induction of M2 alveolar macrophages
Bacterial infections can influence disease outcome in influenza infection; however, the mechanisms mediating these complex interactions remain unclear. Wang et al. reveal how infection with a component of the airway microbiota enhances survival during influenza infection via induction of anti-inflammatory macrophages.
- Jian Wang
- , Fengqi Li
- & Zhigang Tian
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| Open AccessChemical and genetic validation of thiamine utilization as an antimalarial drug target
The malaria parasite Plasmodium falciparum utilizes thiamine for the production of essential enzymatic cofactors. Chan et al. show that inhibition of thiamine utilization with oxythiamine inhibits proliferation of P. falciparumand reduces parasite growth in a mouse model of malaria infection.
- Xie Wah Audrey Chan
- , Carsten Wrenger
- & Kevin J. Saliba