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| Open AccessNeutralization of SARS-CoV-2 Omicron BQ.1, BQ.1.1 and XBB.1 variants following SARS-CoV-2 infection or vaccination in children
In this work, authors investigate the virus-neutralizing capacity in children against circulating BQ.1, BQ.1.1 and XBB.1 SARS-CoV-2 variants. Vaccination induced more neutralizing antibodies against BQ.1.1 and XBB.1 in youngest children ( < 5 years) compared with >5 years children.
- Lorenza Bellusci
- , Gabrielle Grubbs
- & Surender Khurana
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Article
| Open AccessAdults on pre-exposure prophylaxis (tenofovir-emtricitabine) have faster clearance of anti-HIV monoclonal antibody VRC01
Small molecule drugs can affect clearance of monoclonal antibodies, but this hasn’t been assessed for oral HIV-1 pre-exposure prophylaxis. Here, the authors find that faster serum clearance of an experimental IgG1 monoclonal antibody, VRC01, is associated with use of tenofovir-emtricitabine, possibly explained by increased epithelial intestinal permeability.
- Yunda Huang
- , Lily Zhang
- & Maria P. Lemos
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Article
| Open AccessCytolytic circumsporozoite-specific memory CD4+ T cell clones are expanded during Plasmodium falciparum infection
It is important to understand why some individuals in endemic regions acquire natural immunity against malaria while others remain susceptible. Here authors show that during episodes of Plasmodium falciparum malaria, circumsporozoite-specific cytolytic memory CD4+ T cells are clonally expanded in patients, and those with clinical immunity demonstrate reduction in the chemotactic and inhibitory receptor expression in ZEB2+ memory CD4+ T cells.
- Raquel Furtado
- , Mahinder Paul
- & Grégoire Lauvau
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Article
| Open AccessThe genomic epidemiology of shigellosis in South Africa
As a leading cause of diarrhoeal mortality and morbidity, authors examine the epidemiology and genome dynamics of shigellosis in South Africa, utilising whole genome sequence analysis.
- George E. Stenhouse
- , Karen H. Keddy
- & Kate S. Baker
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Comment
| Open AccessOne Health approach at the heart of the French Committee for monitoring and anticipating health risks
Following the COVID-19 pandemic, the French government established a committee for monitoring and anticipating health risks. In this Comment, the authors describe the One Health approach taken by the committee, and outline its aims, composition, and initial actions.
- Thierry Lefrançois
- , Bruno Lina
- & Brigitte Autran
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| Open AccessAntibody-directed evolution reveals a mechanism for enhanced neutralization at the HIV-1 fusion peptide site
Antibodies targeting the HIV-1 fusion peptide rarely achieve more than 60% neutralization breadth. Here, the authors develop an anti-FP antibody enhancing its potency to 80% and structurally resolve the expanded FP-binding site that allows the antibody to target diverse viral variants.
- Bailey B. Banach
- , Sergei Pletnev
- & Brandon J. DeKosky
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Article
| Open AccessIsolation may select for earlier and higher peak viral load but shorter duration in SARS-CoV-2 evolution
The COVID-19 pandemic has seen the emergence of different variants. Analyzing the evolution from the Wuhan strain to the Delta variant, clinical data reveals a fivefold increase in peak viral load and a 1.5-fold faster time to peak.
- Junya Sunagawa
- , Hyeongki Park
- & Ryo Yamaguchi
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Article
| Open AccessEvaluation of the US COVID-19 Scenario Modeling Hub for informing pandemic response under uncertainty
The US COVID-19 Scenario Modeling Hub produced medium to long term projections based on different epidemic scenarios. In this study, the authors evaluate 14 rounds of projections by comparing them to the epidemic trajectories that occurred, and discuss lessons learned for future similar projects.
- Emily Howerton
- , Lucie Contamin
- & Justin Lessler
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Article
| Open AccessWireless, battery-free, multifunctional integrated bioelectronics for respiratory pathogens monitoring and severity evaluation
The SARS-CoV-2 pandemic highlighted our need for methods that allow rapid viral surveillance. Here, authors report a wireless, battery-free and wearable self-diagnosis platform that can continuously capture viral particles, diagnose infection status and evaluate symptom severity via breath and blow.
- Hu Li
- , Huarui Gong
- & Xinge Yu
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Article
| Open AccessDirect-acting antiviral resistance of Hepatitis C virus is promoted by epistasis
This study reveals that mutations of the hepatitis C virus act collectively to confer resistance against direct-acting antiviral drugs. This can aid the development of drugs that are less prone to resistance.
- Hang Zhang
- , Ahmed Abdul Quadeer
- & Matthew R. McKay
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Article
| Open AccessThe burden of post-acute COVID-19 symptoms in a multinational network cohort analysis
Post-acute COVID-19 condition is difficult to quantify because it includes a range of symptoms that may have other causes. In this study, the authors use primary care data from England and Catalonia, Spain, to estimate the incidence of the condition and identify symptoms that occur more frequently following infection than in uninfected controls.
- Kristin Kostka
- , Elena Roel
- & Annika M. Jödicke
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Article
| Open AccessSingle cell transcriptomics shows that malaria promotes unique regulatory responses across multiple immune cell subsets
The use of single cell sequencing has enabled more detailed analysis of the immune response to infection. Here the authors characterise the immune response to malaria infection in an endemic region using single cell transcriptomics indicating regulatory signatures associated with infection.
- Nicholas L. Dooley
- , Tinashe G. Chabikwa
- & Michelle J. Boyle
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Article
| Open AccessInterferon stimulated immune profile changes in a humanized mouse model of HBV infection
There is increasing evidence that treatment of hepatitis B with interferon alpha can be beneficial. Here, Wang et al, present a type 1 interferon receptor humanized mouse model and characterize it as a platform in which to study interferon function in vivo.
- Yaping Wang
- , Liliangzi Guo
- & Feng Li
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Article
| Open AccessMultiplexed detection of viral antigen and RNA using nanopore sensing and encoded molecular probes
Fast discrimination of SARS-CoV-2 variants in clinical samples remains a challenge. Here, authors report on single molecule nanopore sensing combined with DNA molecular probes to simultaneously detect various antigens and RNA mutations of SARS-CoV-2 variants in patient samples.
- Ren Ren
- , Shenglin Cai
- & Joshua B. Edel
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Article
| Open AccessImpact of vaccinations, boosters and lockdowns on COVID-19 waves in French Polynesia
In this study, the authors develop a mathematical modelling framework to estimate the impacts of non-pharmaceutical interventions and vaccination on COVID-19 incidence. The model accounts for changes in SARS-CoV-2 variant and population immunity, and here they use it to investigate epidemic dynamics in French Polynesia.
- Lloyd A. C. Chapman
- , Maite Aubry
- & Adam J. Kucharski
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Article
| Open AccessMalaria surveillance reveals parasite relatedness, signatures of selection, and correlates of transmission across Senegal
Senegal has initiated a national sentinel surveillance program for malaria parasite genetics. Here, the authors report data from the first year of the program and use it to investigate local malaria incidence, patterns of transmission, and genetic loci under selection.
- Stephen F. Schaffner
- , Aida Badiane
- & Sarah K. Volkman
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Article
| Open AccessEnterohaemorrhagic E. coli utilizes host- and microbiota-derived L-malate as a signaling molecule for intestinal colonization
Here, Liu et al show that enterohaemorrhagic Escherichia coli utilizes host- and microbiota-derived L-malate as an essential nutrient and signalling molecule to promote its growth and colonization in the large intestine.
- Bin Liu
- , Lingyan Jiang
- & Bin Yang
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Article
| Open AccessSingle cell spatial analysis reveals inflammatory foci of immature neutrophil and CD8 T cells in COVID-19 lungs
Mathematical tools can be used to help identify pathological features from images of diseased lungs. Here, the authors used mathematical tools combined with high resolution multiplex imaging mass cytometry to show an association between immature neutrophils, CD8 T cells and proliferating alveolar epithelial cells in areas of maximal alveolar damage in COVID-19 lungs.
- Praveen Weeratunga
- , Laura Denney
- & Ling-Pei Ho
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Article
| Open AccessInadequate structural constraint on Fab approach rather than paratope elicitation limits HIV-1 MPER vaccine utility
It is still unclear why HIV-1 vaccines targeting MPER induce antibodies that fail to bind HIV. Here, the authors show that antibodies targeting membrane-proximal linear epitopes of virion spike proteins must generate relevant antibody paratopes and approach angles to ligate their quarry in a topologically restricted site.
- Kemin Tan
- , Junjian Chen
- & Mikyung Kim
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Article
| Open AccessProbabilities of developing HIV-1 bNAb sequence features in uninfected and chronically infected individuals
Successful induction of broadly neutralizing antibodies is a main challenge in HIV vaccine development. The authors provide a framework to determine probabilities of antibody sequence development and show that uninfected and chronically infected individuals have the same chances to develop HIV-1 neutralizing antibodies.
- Christoph Kreer
- , Cosimo Lupo
- & Florian Klein
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Article
| Open AccessA combined adjuvant approach primes robust germinal center responses and humoral immunity in non-human primates
Protein antigens, such as HIV envelope protein, require adjuvants for high immunogenicity. Here the authors show that a combined adjuvant approach with slow antigen delivery and potent ISCOMs adjuvant primes robust germinal center activity and humoral immunity in non-human primates. pSer-modified antigen shifts immunodominance to allow subdominant epitope-targeting of rare B cells.
- Ivy Phung
- , Kristen A. Rodrigues
- & Shane Crotty
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Article
| Open AccessIL-17 signalling is critical for controlling subcutaneous adipose tissue dynamics and parasite burden during chronic murine Trypanosoma brucei infection
Trypanosome brucei is known to colonise the subcutaneous white adipose tissue and the interaction with the cellular locale could play key roles in pathogenesis and host response. Here the author’s use single cell approaches and in vivo animal models, and show a role for IL-17 in the adipose tissue response and parasite burden in a chronic murine model of infection.
- Matthew C. Sinton
- , Praveena R. G. Chandrasegaran
- & Juan F. Quintana
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Article
| Open AccessStructural basis for the toxicity of Legionella pneumophila effector SidH
Legionella pneumophila secretes hundreds of effectors to facilitate infection. Here, Sharma et al show that the virulence effector SidH adopts a unique α-helical conformation, leading to toxicity via tRNA binding site and resolve the structural basis of SidH regulation through ubiquitination.
- Rahul Sharma
- , Michael Adams
- & Sagar Bhogaraju
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Article
| Open AccessDistinct receptor binding domain IgG thresholds predict protective host immunity across SARS-CoV-2 variants and time
Evidence from trials suggests SARS-CoV-2 binding antibody thresholds could serve as surrogate markers of neutralising capacity, but whether this is accurate in the context of variants of concerns, or in the event of prior infection or vaccination remains unclear. Authors explore the performance of receptor binding domain IgG thresholds in predicting a level of neutralising capacity that has demonstrated protection against infection in vaccine trials
- Grace Kenny
- , Sophie O’Reilly
- & Patrick Mallon
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Article
| Open AccessProduction of leishmanin skin test antigen from Leishmania donovani for future reintroduction in the field
As leishmaniasis control programs and new vaccines are advancing, it is necessary to re-introduce the leishmanin skin test to monitor transmission and immunity. This study describes the generation and validation of a new leishmanin skin test antigen for future re-introduction into endemic countries.
- Ranadhir Dey
- , Jalal Alshaweesh
- & Greg Matlashewski
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Article
| Open AccessDefining neutralization and allostery by antibodies against COVID-19 variants
Here, Tulsian et al. identified the effect of biologically relevant full-length IgG binding on the Spike protein from different SARS-CoV-2 variants to comprehensively understand the mechanisms of antibody evasion, towards the development of better antiviral strategies.
- Nikhil Kumar Tulsian
- , Raghuvamsi Venkata Palur
- & Paul Anthony MacAry
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Comment
| Open AccessLessons for cross-species viral transmission surveillance from highly pathogenic avian influenza Korean cat shelter outbreaks
In this Comment, the authors describe recent outbreaks of highly pathogenic avian influenza in cat shelters in Seoul, South Korea. They discuss potential routes of transmission and describe implications for surveillance of spillover infections in animals in non-agricultural settings.
- Younjung Kim
- , Guillaume Fournié
- & Pierre Nouvellet
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Article
| Open AccessSelf-promoted electroactive biomimetic mineralized scaffolds for bacteria-infected bone regeneration
Infected bone defects are a major challenge in orthopedic treatment. Here, the authors develop an electroactive mineralized scaffold that achieves nearly complete in situ healing of infected bone in rats, rabbits and beagle dogs.
- Zixin Li
- , Danqing He
- & Yan Liu
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Article
| Open AccessInferring bacterial transmission dynamics using deep sequencing genomic surveillance data
Studying rare genetic changes that arose as an infectious bacterium spread between lab mice, here the authors show that using the relative abundance of any changes rather than just whether they occurred can more precisely identify who likely infected who.
- Madikay Senghore
- , Hannah Read
- & Siouxsie Wiles
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Article
| Open AccessAntiviral responses in a Jamaican fruit bat intestinal organoid model of SARS-CoV-2 infection
Bats are natural reservoirs for several zoonotic viruses including SARS-CoV-2 thus there is a need to better define bat antiviral responses. Here, Hashimi et al. profile antiviral responses to SARS-CoV-2 in bat intestinal organoids finding that interferon and regenerative responses where induced.
- Marziah Hashimi
- , T. Andrew Sebrell
- & Diane Bimczok
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Article
| Open AccessImpact of COVID-19 on mortality in coastal Kenya: a longitudinal open cohort study
SARS-CoV-2-associated mortality estimates for sub-Saharan Africa are uncertain due to lack of comprehensive surveillance systems. Here, the authors analyse data from a detailed surveillance system in Kilifi, Kenya and find that excess mortality rates were relatively low, except for older adults.
- M. Otiende
- , A. Nyaguara
- & J. A. G. Scott
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Article
| Open AccessEffectiveness of the second COVID-19 booster against Omicron: a large-scale cohort study in Chile
This study assesses the effectiveness of a second COVID-19 mRNA booster vaccine against severe disease using data from Chile. The authors find that the effectiveness of the second mRNA booster was high with a range of different background vaccination schemes, but there was evidence of waning over time.
- Alejandro Jara
- , Cristobal Cuadrado
- & Rafael Araos
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Article
| Open AccessPasteurella sp. associated with fatal septicaemia in six African elephants
A series of unexplained elephant mortalities occurred in northwest Zimbabwe in 2020. Here the authors show that six elephants died of bacterial septicaemia associated with a little-reported Pasteurella species.
- Chris M. Foggin
- , Laura E. Rosen
- & Falko Steinbach
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Article
| Open AccessLong-term health impacts of COVID-19 among 242,712 adults in England
The duration of symptomatic COVID-19 and its impacts on health and quality of life are not well understood. In this study, the authors report results from a survey of ~275,000 adults in England and find that persistent COVID-19 is relatively rare but is associated with poorer mental health and health-related quality of life.
- Christina J. Atchison
- , Bethan Davies
- & Paul Elliott
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Article
| Open AccessC-type lectin receptor 2d forms homodimers and heterodimers with TLR2 to negatively regulate IRF5-mediated antifungal immunity
Receptor dimerization can modulate immune responses during various microbial infections. Here, the authors show that C-type lectin receptor-2d (CLEC2D) negatively regulates antifungal immunity through forming homodimers or heterodimers with TLR2.
- Fan Li
- , Hui Wang
- & Xin-Ming Jia
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Article
| Open AccessPathogen-driven degradation of endogenous and therapeutic antibodies during streptococcal infections
Group A streptococcus causes a wide range of human diseases and significantly contributes to morbidity and mortality worldwide. Here, Toledo et al show how streptococcus alters the structure and function of endogenous and therapeutic antibodies during infection and how this is affected by the host microenvironment.
- Alejandro Gomez Toledo
- , Eleni Bratanis
- & Johan Malmström
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Article
| Open AccessIndividual level analysis of digital proximity tracing for COVID-19 in Belgium highlights major bottlenecks
Digital proximity tracing apps were widely used during the COVID-19 pandemic but have not been thoroughly evaluated. Here, the authors use data from students in Leuven, Belgium and estimate that apps notified only ~4% exposed contacts, had a 1–2 day delay for notification, and identified fewer infected contacts than manual contact tracing.
- Caspar Geenen
- , Joren Raymenants
- & Emmanuel André
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Article
| Open AccessActivation of coagulation and proinflammatory pathways in thrombosis with thrombocytopenia syndrome and following COVID-19 vaccination
Adenovirus-based vaccination for SARS-CoV-2 has a rare chance to cause thrombosis with thrombocytopenia (TTS). Here the authors compare proteomic and transcriptomic data from vaccinated participants with or without TTS to find distinct activations of coagulation and innate immune pathways in patient with TTS, or following initial or boosting vaccination.
- Malika Aid
- , Kathryn E. Stephenson
- & Dan H. Barouch
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Article
| Open AccessStructure-function analyses reveal key molecular determinants of HIV-1 CRF01_AE resistance to the entry inhibitor temsavir
The HIV-1 entry inhibitor temsavir prevents the interaction of the envelope glycoprotein with its cellular receptor. Here, authors apply CryoEM to show that HIV-1 clade AE resistance to temsavir is a combination of the residue at position 375 (His) and mutations in the gp120 mobile layers. Mutation of His375 to Ser/Thr and reversion of the layer mutations are required to restore temsavir sensitivity.
- Jérémie Prévost
- , Yaozong Chen
- & Marzena Pazgier
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Article
| Open AccessA genomic appraisal of invasive Salmonella Typhimurium and associated antibiotic resistance in sub-Saharan Africa
Invasive Salmonella Typhimurium bloodstream infection causes a significant public health burden in sub-Saharan Africa. Here, the authors analyse whole genome sequences of 1,302 S. Typhimurium isolates from Africa and describe its evolution, geographic spread, and antimicrobial resistance characteristics.
- Sandra Van Puyvelde
- , Tessa de Block
- & Octavie Lunguya
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Article
| Open AccessAn innate granuloma eradicates an environmental pathogen using Gsdmd and Nos2
Pathogens often persist within granulomas which form to control infection. Here, Harvest et al describe an innate granuloma that eradicates a ubiquitous environmental pathogen without inducing adaptive immunity.
- Carissa K. Harvest
- , Taylor J. Abele
- & Edward A. Miao
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Article
| Open AccessThe transcription factor Zeb1 controls homeostasis and function of type 1 conventional dendritic cells
Type 1 conventional dendritic cells (cDC1) play a pivotal role in the cross-presentation of antigens, enabling efficient CD8 + T cell response. Here authors show that the transcription factor Zeb1 essentially regulates this process via facilitating the reactive-oxygen-species-dependent rupture of phagosomal membrane to allow antigen export to the cytoplasm.
- Yan Wang
- , Quan Zhang
- & Nengming Xiao
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Article
| Open AccessCD8+ T cells control SIV infection using both cytolytic effects and non-cytolytic suppression of virus production
Control of HIV and SIV infection is largely thought to be achieved through direct lysis of target cells. Here, using mathematical modelling of viral load data from rhesus macaques, the authors propose that virus control is best explained by the combination of cytolytic and non-cytolytic effects.
- Benjamin B. Policicchio
- , Erwing Fabian Cardozo-Ojeda
- & Ruy M. Ribeiro
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Article
| Open AccessEpidemiology of Plasmodium malariae and Plasmodium ovale spp. in Kinshasa Province, Democratic Republic of Congo
Non-falciparum malaria may cause a significant disease burden in highly endemic regions, but epidemiological data is limited. In this study, the authors estimate the incidence and prevalence of P. malariae, P. ovale spp., in Kinshasa, Democratic Republic of Congo and compare to P. falciparum, which known to be common in the region.
- Rachel Sendor
- , Kristin Banek
- & Jonathan B. Parr
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Article
| Open AccessObesity dysregulates the pulmonary antiviral immune response
Obesity is a risk factor for severe influenza infection. Here, Almond et al show that increased susceptibility is due to increased airway concentrations of the hormone leptin which dampens interferon responses and facilitates severe infection.
- Mark Almond
- , Hugo A. Farne
- & Aran Singanayagam
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Article
| Open AccessCryptococcus neoformans adapts to the host environment through TOR-mediated remodeling of phospholipid asymmetry
Here, Ristow et al show that the environmental fungus Cryptococcus adapts to the higher carbon dioxide levels present in human tissue through activation of the Target-of-Rapamycin stress response pathway leading to reorganization of its outer membrane lipids and host adaptation.
- Laura C. Ristow
- , Andrew J. Jezewski
- & Damian J. Krysan
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Article
| Open AccessA spatial sequencing atlas of age-induced changes in the lung during influenza infection
Ageing is known to impair the immune response against infectious pathogens. Here, Kasmani et al. present a spatial and transcriptomic atlas of immune changes in the lungs of young and aged mice in response to influenza virus infection.
- Moujtaba Y. Kasmani
- , Paytsar Topchyan
- & Weiguo Cui
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Article
| Open AccessAssessing the global risk of typhoid outbreaks caused by extensively drug resistant Salmonella Typhi
Extensively drug resistant (XDR) typhoid fever is an emerging global health threat. This study compares data on air travel patterns and typhoid incidence to identify countries at high risk for XDR typhoid outbreaks.
- Joseph Walker
- , Chrispin Chaguza
- & Virginia E. Pitzer
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Article
| Open AccessCryptic susceptibility to penicillin/β-lactamase inhibitor combinations in emerging multidrug-resistant, hospital-adapted Staphylococcus epidermidis lineages
Staphylococcus epidermidis can cause invasive infections that are difficult to treat due to multi-resistance to most clinically relevant drugs, including methicillin and other β-lactam antibiotics, vancomycin, and rifampicin. In this work, the authors use in vitro assays and a mouse infection model to explore cryptic susceptibility and development of resistance to penicillin/β-lactamase combinations.
- Xiaoliang Ba
- , Claire L. Raisen
- & Jesper Larsen