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| Open AccessCross-reactive serum and memory B-cell responses to spike protein in SARS-CoV-2 and endemic coronavirus infection
Pre-existing immune responses between antigenically related viruses can influence responses in viral infections or vaccinations. Here the authors assess and characterize the presence of antibody and memory B cell populations specific to SARS-CoV2 and endemic human coronaviruses.
- Ge Song
- , Wan-ting He
- & Raiees Andrabi
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Article
| Open AccessMycobacterium tuberculosis precursor rRNA as a measure of treatment-shortening activity of drugs and regimens
It is unclear why different antibiotics vary in their ability to shorten treatment of tuberculosis. Here, the authors show that a measure based on ribosomal RNA synthesis in Mycobacterium tuberculosis correlates with treatment shortening in culture, in mice and in human studies.
- Nicholas D. Walter
- , Sarah E. M. Born
- & Martin I. Voskuil
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Article
| Open AccessThe effect of generic market entry on antibiotic prescriptions in the United States
Generics contribute to increased availability of antibiotics, benefiting healthcare systems but potentially leading to increased consumption with implications for antibiotic stewardship and resistance. Here, the authors found no consistent changes in prescribing patterns of the 13 antibiotics that entered the US market as generics from 2000–2012.
- Cecilia Kållberg
- , Jemma Hudson
- & Ramanan Laxminarayan
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Article
| Open AccessPhospholipid translocation captured in a bifunctional membrane protein MprF
The Multiple Peptide Resistance Factors (MprFs) utilize two separate domains to synthesize and translocate aminoacyl phospholipids to the outer leaflets of bacterial membranes. Here authors present cryo-electron microscopy structures of MprF homodimer from Rhizobium tropici (RtMprF) at two different states in complex with lysyl-phosphatidylglycerol (LysPG).
- Danfeng Song
- , Haizhan Jiao
- & Zhenfeng Liu
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Article
| Open AccessGene-level metagenomic architectures across diseases yield high-resolution microbiome diagnostic indicators
Here, combing the massive gene-universe of the gut microbiome to identify strain-specific, cross-disease, associations across seven human diseases, the authors introduce the concept of microbiome architecture, defined as the complete set of positive and negative associations between microbial genes and human host disease, highlighting microbiome architectures as potential diagnostic indicators.
- Braden T. Tierney
- , Yingxuan Tan
- & Chirag J. Patel
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Article
| Open AccessFunctional and structural characterization of a two-MAb cocktail for delayed treatment of enterovirus D68 infections
Although enterovirus D68 poses a major global threat to children, neither vaccines nor therapeutics are currently available. Using Cryo-EM, Zhang et al. show that two murine-derived monoclonal antibodies with therapeutic efficacy neutralize virions via binding to the canyon region, creating steric hindrance for sialic acid receptor binding.
- Chao Zhang
- , Cong Xu
- & Zhong Huang
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Article
| Open AccessToxoplasma LIPIN is essential in channeling host lipid fluxes through membrane biogenesis and lipid storage
Apicomplexa generate essential lipids as combination of host fatty acids and de novo synthesized within the apicoplast. Here, the authors identify a phosphatidic acid phosphatase in Toxoplasma gondii, TgLIPIN, as central for controlled lipid synthesis and define the host-scavenged lipidome.
- Sheena Dass
- , Serena Shunmugam
- & Cyrille Y. Botté
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Article
| Open AccessA global resource for genomic predictions of antimicrobial resistance and surveillance of Salmonella Typhi at pathogenwatch
Whole genome sequencing data are increasingly becoming routinely available but generating actionable insights is challenging. Here, the authors describe Pathogenwatch, a web tool for genomic surveillance of S. Typhi, and demonstrate its use for antimicrobial resistance assignment and strain risk assessment.
- Silvia Argimón
- , Corin A. Yeats
- & David M. Aanensen
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Article
| Open AccessIL-21 and IFNα therapy rescues terminally differentiated NK cells and limits SIV reservoir in ART-treated macaques
Infection of African green monkeys with SIV is associated with reduced pathogenicity. Here the authors explore the requirement of differentiated NK cell populations in a pathogenic Rhesus macaque model of SIV infection and show administration of IL-21 and IFNα rescues terminally differentiated NK cells, similarly to what found in African green monkeys, and limits the SIV reservoir in antiretroviral therapy treated macaques.
- Justin Harper
- , Nicolas Huot
- & Mirko Paiardini
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Article
| Open AccessLongitudinal in vivo imaging of acute neuropathology in a monkey model of Ebola virus infection
The neurological effects of Ebola disease in the acute stage are not well-described. Here, the authors use longitudinal in vivo neuroimaging and immunohistochemistry to assess pathological changes in the central nervous system in a non-human primate model of Ebola virus infection.
- William Schreiber-Stainthorp
- , Jeffrey Solomon
- & Dima A. Hammoud
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Article
| Open AccessHeterologous vaccination regimens with self-amplifying RNA and adenoviral COVID vaccines induce robust immune responses in mice
Heterologous vaccination regimens for COVID-19 could be useful for example if there is a shortage of one vaccine type. Here, Spencer et al. show that heterologous vaccination with a self-amplifying RNA vaccine and an adenoviral vectored vaccine performs at least as well as the homologous vaccinations in mice.
- Alexandra J. Spencer
- , Paul F. McKay
- & Teresa Lambe
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Article
| Open AccessCrystal structure of SARS-CoV-2 Orf9b in complex with human TOM70 suggests unusual virus-host interactions
SARS-CoV-2 orf9b binds to the mitochondrial outer membrane protein TOM70 and has been linked to the suppression of interferon responses. Here, the authors characterize the interactions of SARS-CoV-2 orf9b and human TOM70 biochemically, and they determine the 2.2 Å crystal structure of the TOM70 cytosolic domain with a bound SARS-CoV-2 orf9b peptide.
- Xiaopan Gao
- , Kaixiang Zhu
- & Sheng Cui
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Article
| Open AccessTargeting human Acyl-CoA:cholesterol acyltransferase as a dual viral and T cell metabolic checkpoint
Shared metabolic pathways could allow simultaneous manipulation of T cells, viruses and tumours. Here the authors show targeting cholesterol esterification restrains hepatitis B in vitro, whilst bolstering exhausted antigen-specific T cell responses from human liver and hepatocellular carcinoma.
- Nathalie M. Schmidt
- , Peter A. C. Wing
- & Mala K. Maini
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Article
| Open AccessCharacterization of an attenuated SARS-CoV-2 variant with a deletion at the S1/S2 junction of the spike protein
The S1/S2 junction of the SARS-CoV-2 Spike protein is emerging as a key factor in virulence and pathogenesis. Here, the authors characterise an attenuated strain of SARS-CoV-2 with deletions in the critical S1/S2 junction and observe enhanced replication, generation of potent adaptive immunity but reduced immunopathology in a hamster model of infection.
- Pui Wang
- , Siu-Ying Lau
- & Honglin Chen
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Article
| Open AccessAnalysis of Zika virus capsid-Aedes aegypti mosquito interactome reveals pro-viral host factors critical for establishing infection
Here the authors develop mosquito cell lines expressing Zika virus (ZIKV) capsid and perform proteomics experiments retrieving 157 protein interactors, of which they show 8 to act as pro-viral factors, showing the transitional endoplasmic reticulum 94 (TER94) and its human ortholog VCP target ZIKV capsid to proteasomal degradation to facilitate infection.
- Rommel J. Gestuveo
- , Jamie Royle
- & Margus Varjak
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Article
| Open AccessPlant DNA polymerases α and δ mediate replication of geminiviruses
Geminiviruses cause substantial damage to crops worldwide. Here Wu et al. show that geminivirus replication relies upon the host DNA polymerases α and δ, which produce double-stranded DNA intermediates and new copies of the viral genome, respectively, and is modulated by the viral C3 protein.
- Mengshi Wu
- , Hua Wei
- & Rosa Lozano-Durán
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Article
| Open AccessINI1/SMARCB1 Rpt1 domain mimics TAR RNA in binding to integrase to facilitate HIV-1 replication
HIV-1 integrase (IN) binds the host factor INI1/SMARCB1, which is required at multiple stages of HIV-1 replication. Here, the authors show that the same IN residues are involved in INI1 and RNA binding and in influencing particle morphogenesis and suggest that the IN-binding INI1 domain is structurally similar to HIV TAR RNA.
- Updesh Dixit
- , Savita Bhutoria
- & Ganjam V. Kalpana
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Article
| Open AccessCommunity composition of microbial microcosms follows simple assembly rules at evolutionary timescales
Evolution affects microbial community composition, but it is still unknown how commonly compositions change, and how predictable such changes are. Using experimental evolution, Meroz et al. show that compositional changes typically occur within ~400 generations, and are predictable by a bottom-up approach.
- Nittay Meroz
- , Nesli Tovi
- & Jonathan Friedman
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Article
| Open AccessEstimating COVID-19 mortality in Italy early in the COVID-19 pandemic
Estimates of COVID-19-related mortality are limited by incomplete testing. Here, the authors perform counterfactual analyses and estimate that there were 59,000–62,000 deaths from COVID-19 in Italy until 9th September 2020, approximately 1.5 times higher than official statistics.
- Chirag Modi
- , Vanessa Böhm
- & Uroš Seljak
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Article
| Open AccessLying in wait: the resurgence of dengue virus after the Zika epidemic in Brazil
Zika and dengue incidence in the Americas declined in 2017–2018, but dengue resurged in 2019 in Brazil. This study uses epidemiological, climatological and genomic data to show that the decline of dengue may be explained by protective immunity from pre-exposure to ZIKV and/or DENV in prior years.
- Anderson Fernandes Brito
- , Lais Ceschini Machado
- & Nathan D. Grubaugh
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Article
| Open AccessVariability of plasmid fitness effects contributes to plasmid persistence in bacterial communities
The variability of plasmid fitness effects on wild-type bacterial hosts have been largely unknown until this study, which shows that plasmid persistence increases with bacterial diversity and becomes less dependent on conjugation. This could explain why plasmids remain so common in nature.
- Aida Alonso-del Valle
- , Ricardo León-Sampedro
- & Alvaro San Millán
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Article
| Open AccessGenomic analyses of Mycobacterium tuberculosis from human lung resections reveal a high frequency of polyclonal infections
Polyclonal infections occur when at least two unrelated strains of the same pathogen are detected in an individual. Here, Moreno-Molina et al. analyse sputum and surgical resections from tuberculosis patients, showing that the magnitude of polyclonal infections can be underestimated when only testing sputum samples.
- Miguel Moreno-Molina
- , Natalia Shubladze
- & Iñaki Comas
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Article
| Open AccessTaxonomic signatures of cause-specific mortality risk in human gut microbiome
Gut microbiome composition has a role in health and disease. Here the authors show that microbiome signatures related to the Enterobacteriaceae family are associated with cause-specific mortality risk in a well phenotyped Finish population over a 15-year follow-up.
- Aaro Salosensaari
- , Ville Laitinen
- & Teemu Niiranen
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Article
| Open AccessSingle-component multilayered self-assembling nanoparticles presenting rationally designed glycoprotein trimers as Ebola virus vaccines
Ebola virus glycoprotein (GP) is a major target for vaccine design. Here, the authors identify mutations to improve GP stability and yield, design two multilayered nanoparticle carriers, and demonstrate good immunogenicity of the modified GP on nanoparticles in mice and rabbits.
- Linling He
- , Anshul Chaudhary
- & Jiang Zhu
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Article
| Open AccessA SARS-CoV-2 neutralizing antibody with extensive Spike binding coverage and modified for optimal therapeutic outcomes
Antibodies against SARS-CoV-2 S protein can provide a treatment strategy for COVID-19. Here, Guo et al. provide the crystal structure of a SARS-CoV2 neutralizing antibody isolated from a convalescent patient and highlight the therapeutic efficacy in a rhesus monkey model of an engineered version with optimized pharmacokinetic and safety profile.
- Yu Guo
- , Lisu Huang
- & Zihe Rao
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Article
| Open AccessThe RNA binding protein FgRbp1 regulates specific pre-mRNA splicing via interacting with U2AF23 in Fusarium
Human RBM42 associates with the spliceosome complex. Here the authors show that the fungus counterpart of RBM42, FgRbp1 regulates splicing by interacting with FgU2AF23.
- Minhui Wang
- , Tianling Ma
- & Zhonghua Ma
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Article
| Open AccessMacrocyclic peptides exhibit antiviral effects against influenza virus HA and prevent pneumonia in animal models
Here, the authors report bi-functional, wide tropic macrocycles that bind the influenza viral envelope protein hemagglutinin and inhibit virus infection by blocking adsorption and fusion and show efficacy in preventing severe pneumonia at later stages of infection in mouse and non-human primate cynomolgus macaque models.
- Makoto Saito
- , Yasushi Itoh
- & Michinori Kohara
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Article
| Open AccessSARS-CoV-2 gene content and COVID-19 mutation impact by comparing 44 Sarbecovirus genomes
The SARS-CoV-2 gene set remains unresolved, hindering dissection of COVID-19 biology. Comparing 44 Sarbecovirus genomes provides a high-confidence protein-coding gene set. The study characterizes protein-level and nucleotide-level evolutionary constraints, and prioritizes functional mutations from the ongoing COVID-19 pandemic.
- Irwin Jungreis
- , Rachel Sealfon
- & Manolis Kellis
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Article
| Open AccessGlobal population structure and genotyping framework for genomic surveillance of the major dysentery pathogen, Shigella sonnei
Whole genome sequencing is increasingly being adopted for Shigella sonnei outbreak investigation and surveillance, but there is no global classification standard. Here, the authors develop and validate a genomic framework implemented using open-source software, and demonstrate its application using surveillance data.
- Jane Hawkey
- , Kalani Paranagama
- & Kathryn E. Holt
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Article
| Open AccessStructural visualization of transcription activated by a multidrug-sensing MerR family regulator
The MerR family of transcriptional regulators, such as EcmrR, activate promoters with a structure that is suboptimal for recognition by RNA polymerase holoenzyme. Structural insights into the EcmrR-dependent transcription process elucidate the mechanisms enabling optimal promoter recognition and transition from initiation to elongation.
- Yang Yang
- , Chang Liu
- & Bin Liu
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Article
| Open AccessA SARS-CoV-2 antibody curbs viral nucleocapsid protein-induced complement hyperactivation
While SARS-CoV-2 S protein targeting monoclonal antibodies (mAbs) are well studied, little is known about N protein-targeting mAbs. Here, Kang et al. provide the crystal structure of the N protein RNA binding domain with a mAb derived from a convalescent patient and show that it compromises the N protein-induced complement hyperactivation.
- Sisi Kang
- , Mei Yang
- & Shoudeng Chen
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Article
| Open AccessGut microbiome modulates Drosophila aggression through octopamine signaling
The gut microbiome regulates behaviour in a number of species. Here the authors show that depletion of the gut microbiome in Drosophila reduced aggressive behaviour, in an octopamine-dependent manner.
- Yicong Jia
- , Shan Jin
- & Wei Liu
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Review Article
| Open AccessEmerging concepts in intestinal immune control of obesity-related metabolic disease
At the centre of intestinal health and the fight against obesity and metabolic syndrome is the intestinal microbiota and its interaction with our immune systems. Here the authors Review the current understanding of how these systems interact and how we can capitalize on recent advances to provide better therapeutic options.
- Saad Khan
- , Helen Luck
- & Daniel A. Winer
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Article
| Open AccessAn infection-induced RhoB-Beclin 1-Hsp90 complex enhances clearance of uropathogenic Escherichia coli
Bacterial invasion can lead to multiple host cell responses. Here, the authors show that in a model of uropathogenic E. coli, RhoB is upregulated and induces autophagosome formation in a complex with Beclin1 and Hsp90, promoting bacterial clearance.
- Chunhui Miao
- , Mingyu Yu
- & Quan Wang
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Article
| Open AccessA peptidoglycan storm caused by β-lactam antibiotic’s action on host microbiota drives Candida albicans infection
A risk factor for invasive Candida albicans infection is the use of broad-spectrum antibiotics, but the reasons are poorly understood. Here, the authors show in mice that β-lactam antibiotics cause commensal bacteria to release peptidoglycan fragments that induce the invasive hyphal growth of C. albicans, leading to systemic dissemination.
- Chew Teng Tan
- , Xiaoli Xu
- & Yue Wang
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Article
| Open AccessInterplay of two transcription factors for recruitment of the chromatin remodeling complex modulates fungal nitrosative stress response
Plant and animal tissues produce nitric oxide and reactive nitrogen species that induce nitrosative stress in pathogens. Here, Jian et al. identify two transcriptional regulators in the phytopathogen Fusarium graminearum that control the nitrosative stress response by modulating the recruitment of a chromatin-remodelling complex at the promoters of the response genes.
- Yunqing Jian
- , Zunyong Liu
- & Zhonghua Ma
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Article
| Open AccessStructures of flavivirus RNA promoters suggest two binding modes with NS5 polymerase
Flaviviruses use a ~70 nucleotide stem-loop structure called stem-loop A (SLA) at the 5’ end of the RNA genome as a promoter for RNA synthesis by the viral polymerase NS5. Here the authors describe the structures of dengue and Zika virus SLAs, identify the SLA-binding site on NS5, and propose models for how NS5 recognizes the RNA promoter.
- Eunhye Lee
- , Paul J. Bujalowski
- & Kyung H. Choi
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Article
| Open AccessIFN-γ-dependent NK cell activation is essential to metastasis suppression by engineered Salmonella
Cancer metastasis is one of the major causes of cancer related deaths and there is an urgent need to find more clinically effective metastasis targeting agents. Here, the authors show that Salmonella YB1 inhibits metastasis in multiple mouse models of cancer through a mechanism dependent on IFN-γ and NK cells.
- Qiubin Lin
- , Li Rong
- & Jian-Dong Huang
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Article
| Open AccessHuman kidney is a target for novel severe acute respiratory syndrome coronavirus 2 infection
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to acute kidney injury. The authors describe that SARS-COV-2 can directly infect human kidney, possibly mediating tubular pathogenesis.
- Bo Diao
- , Chenhui Wang
- & Yongwen Chen
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Article
| Open AccessPopulation genomics provides insights into the evolution and adaptation to humans of the waterborne pathogen Mycobacterium kansasii
Mycobacterium kansasii can cause serious pulmonary disease. Here, the authors present a population genomics analysis of 358 environmental and clinical isolates from around the world, supporting the idea that municipal water is a main source of infection, and shedding light into the pathogen’s diversity and adaptation to the human host.
- Tao Luo
- , Peng Xu
- & Qian Gao
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Article
| Open AccessSelective cell death in HIV-1-infected cells by DDX3 inhibitors leads to depletion of the inducible reservoir
DEAD-box polypeptide 3 (DDX3) is a host protein belonging to the family of ATP-dependent RNA helicases. Here, the authors demonstrate that DDX3 inhibitors reverse HIV-1 latency and selectively induce cell death in HIV-1-infected cell lines, primary CD4+ T cells and in CD4+ T cells from cART-suppressed people living with HIV-1.
- Shringar Rao
- , Cynthia Lungu
- & Tokameh Mahmoudi
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Article
| Open AccessEpididymal epithelium propels early sexual transmission of Zika virus in the absence of interferon signaling
Zika virus can be sexually transmitted. Here, Pletnev et al. show in an immunocompromised mouse model that the epithelial cells of the epididymis, rather than cells of the testis, vas deferens, prostate, or seminal vesicles, are the most likely source of male-to-female sexually transmitted ZIKV genomes.
- Alexander G. Pletnev
- , Olga A. Maximova
- & Konstantin A. Tsetsarkin
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Article
| Open AccessEtiological, epidemiological, and clinical features of acute diarrhea in China
Diarrhoea is a major cause of morbidity and mortality in China. Here, the authors present results from a large sentinel surveillance scheme from 217 hospitals in all 31 provinces in mainland China, including ~150,000 patients with acute diarrhoea and covering years 2009-2018.
- Li-Ping Wang
- , Shi-Xia Zhou
- & Jun Wang
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Article
| Open AccessDecrypting bacterial polyphenol metabolism in an anoxic wetland soil
It is thought that polyphenols inhibit organic matter decomposition in soils devoid of oxygen. Here the authors use metabolomics and genome-resolved metaproteomics to provide experimental evidence of polyphenol biodegradation and maintained soil microbial community metabolism despite anoxia.
- Bridget B. McGivern
- , Malak M. Tfaily
- & Kelly C. Wrighton
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Article
| Open AccessReductive evolution and unique predatory mode in the CPR bacterium Vampirococcus lugosii
The Candidate Phyla Radiation (CPR) constitutes a large group of bacterial lineages with small cell sizes and limited biosynthetic capabilities. Here, Moreira et al. study the biology and genome of Vampirococcus lugosii, an epibiotic parasite of other bacteria, supporting parasitism as a common lifestyle of CPR bacteria.
- David Moreira
- , Yvan Zivanovic
- & Purificación López-García
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Article
| Open AccessRapid evolution and host immunity drive the rise and fall of carbapenem resistance during an acute Pseudomonas aeruginosa infection
Here, following a patient with severe acute Pseudomonas aeruginosa infection, the authors combine comprehensive isolate characterization from lung and gut samples (>100 isolates) and patient clinical data to provide insights into bacterial responses to antibiotic therapy.
- Rachel Wheatley
- , Julio Diaz Caballero
- & Craig MacLean
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Comment
| Open AccessBreaking new ground in antimicrobial stewardship in companion animal veterinary practice
Singleton and colleagues publish in Nature Communications an intervention study to reduce antimicrobial usage in companion animal practice. They identify significant reductions in antimicrobial usage with their more active intervention group over approximately a 6-month period. The study offers an exciting way forward to explore further the trial interventions and assess alternative methods to improve antimicrobial stewardship in veterinary practice.
- David Brodbelt
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Article
| Open AccessFtsZ treadmilling is essential for Z-ring condensation and septal constriction initiation in Bacillus subtilis cell division
Bacterial cell division by cell wall synthesis proteins is guided by treadmilling filaments of the cytoskeleton protein FtsZ. Here authors use nanofabrication, advanced microscopy, and microfluidics to resolve the function of FtsZ treadmilling in the Gram-positive model organism Bacillus subtilis.
- Kevin D. Whitley
- , Calum Jukes
- & Séamus Holden
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Article
| Open AccessHigher gametocyte production and mosquito infectivity in chronic compared to incident Plasmodium falciparum infections
In this longitudinal study of an incident (new infections) and chronic (asymptomatic infections) cohort of Plasmodium falciparum infection in children in Burkina Faso, the authors show higher gametocyte production and mosquito infectivity in chronic infections.
- Aissata Barry
- , John Bradley
- & Teun Bousema
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