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| Open AccessAn antiplasmid system drives antibiotic resistance gene integration in carbapenemase-producing Escherichia coli lineages
It has been predicted that mobilization of resistance genes from plasmid to chromosome is selected by an antibiotic pressure. Here, authors discover an antiplasmid system promoting the chromosomal integration of the carbapenemase gene blaOXA-48.
- Pengdbamba Dieudonné Zongo
- , Nicolas Cabanel
- & Isabelle Rosinski-Chupin
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Article
| Open AccessAssessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries
High levels of extended spectrum beta-lactamase (ESBL) and carbapenemase encoding genes were detected in bacterial isolates causing neonatal sepsis in LMICs. Authors assess the in vitro activity of three antibiotics (fosfomycin, flomoxef and amikacin) in combination against ESBL-producing Klebsiella pneumoniae and Escherichia coli isolates.
- Biljana Kakaraskoska Boceska
- , Tuba Vilken
- & Herman Goossens
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Article
| Open AccessAccurate and rapid antibiotic susceptibility testing using a machine learning-assisted nanomotion technology platform
Sturm et. al developed a 2 to 4 h antibiotic susceptibility test based on bacterial vibrations. This diagnostic test applies to the most frequently found gram-negative bacteria in bloodstream infections and demonstrates its potential in contributing to faster treatment decisions.
- Alexander Sturm
- , Grzegorz Jóźwiak
- & Danuta Cichocka
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Article
| Open AccessDeep learning model for personalized prediction of positive MRSA culture using time-series electronic health records
Identification of patients at high risk of methicillin-resistant Staphylococcus aureus (MRSA) infection could improve treatment outcomes by optimising antimicrobial therapy. Here the authors develop a deep learning model that uses electronic health record data from the United States to predict MRSA culture positivity.
- Masayuki Nigo
- , Laila Rasmy
- & Degui Zhi
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Article
| Open AccessThe plasmidome associated with Gram-negative bloodstream infections: A large-scale observational study using complete plasmid assemblies
Plasmids carry antimicrobial resistance genes and contribute to the rapid dissemination of resistance. Here, the authors sequence 1,880 complete plasmids from 738 isolates from bloodstream infections, shedding light on the links between plasmid types, bacterial hosts and antimicrobial resistance.
- Samuel Lipworth
- , William Matlock
- & Nicole Stoesser
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Article
| Open AccessDefining the biogeographical map and potential bacterial translocation of microbiome in human ‘surface organs’
Given that the human body is composed of many microbial niches, and there have been few reports on the biogeography of the microbiome, the authors analyse the intra-individual inter-organ and intra-organ microbiome of seven surface organs of deceased individuals.
- Jun-Jun She
- , Wei-Xin Liu
- & Jun Yu
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Article
| Open AccessIncrease in antioxidant capacity associated with the successful subclone of hypervirulent carbapenem-resistant Klebsiella pneumoniae ST11-KL64
Plasmid acquisition imposes an adaptive burden, which can be ameliorated by host-plasmid coevolution. Here, the authors characterise virulence plasmids of carbapenem-resistant Klebsiella pneumoniae, and show the discard of certain sequences to enhance survival, conferring an evolutionary advantage.
- Ruobing Wang
- , Anru Zhang
- & Hui Wang
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Article
| Open AccessMicrobial co-occurrences on catheters from long-term catheterized patients
The authors examine temporal polymicrobial community composition in patients with long-term urinary catheters to identify species co-occurrences and demonstrate uropathogenic Escherichia coli augments growth of a prevalent opportunistic uropathogen in urine.
- Taylor M. Nye
- , Zongsen Zou
- & Scott J. Hultgren
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Article
| Open AccessAirway environment drives the selection of quorum sensing mutants and promote Staphylococcus aureus chronic lifestyle
This study by Ding et al reveals that the quorum-sensing dysfunction typically encountered in lung-adapted Staphylococcus aureus isolates could be selected by an enhanced ability to consume sialic acid released from airway mucins by the microbiota.
- Xiongqi Ding
- , Catherine Robbe-Masselot
- & Anne Jamet
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Article
| Open AccessKlebsiella pneumoniae clinical isolates with features of both multidrug-resistance and hypervirulence have unexpectedly low virulence
Convergent strains, those containing characteristics of both multidrug-resistant & hypervirulent Klebsiella pneumoniae, are a global threat to public health. In this work, authors analyse convergent isolates from the United States and reveal unexpectantly low virulence.
- Travis J. Kochan
- , Sophia H. Nozick
- & Alan R. Hauser
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Article
| Open AccessQuorum-sensing synthase mutations re-calibrate autoinducer concentrations in clinical isolates of Pseudomonas aeruginosa to enhance pathogenesis
Simanek et al. discovered variants that arise in the protein responsible for synthesizing a molecule required for bacterial communication, which mediates the progression of virulence in the pathogen Pseudomonas aeruginosa.
- Kayla A. Simanek
- , Megan L. Schumacher
- & Jon E. Paczkowski
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Article
| Open AccessRNA is a key component of extracellular DNA networks in Pseudomonas aeruginosa biofilms
The roles of extracellular RNAs present in bacterial biofilms are poorly understood. Here, Mugunthan et al. show that specific mRNAs associate with extracellular DNA in the matrix of bacterial biofilms, facilitating the formation of viscoelastic networks.
- Sudarsan Mugunthan
- , Lan Li Wong
- & Thomas Seviour
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Article
| Open AccessDiagnostic and commensal Staphylococcus pseudintermedius genomes reveal niche adaptation through parallel selection of defense mechanisms
Staphylococcus pseudintermedius has a wide host-range in domesticated and wild animals, yet it has also been isolated as an opportunistic pathogen in human wounds. In this work, the authors genotypically analyse S. pseudintermedius isolates from veterinary diagnostic laboratories and medical care centres, alongside household surfaces and inhabitants.
- Sanjam S. Sawhney
- , Rhiannon C. Vargas
- & Gautam Dantas
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Article
| Open AccessHierarchical AI enables global interpretation of culture plates in the era of digital microbiology
DeepColony is a multi-level AI solution for the interpretation of bacterial culturing images in clinical microbiology laboratory automations. Here, the authors show it allows presumptive identification and quantitation of relevant pathogens at both colony- and plate-level.
- Alberto Signoroni
- , Alessandro Ferrari
- & Karissa Culbreath
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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 AccessDisease-specific loss of microbial cross-feeding interactions in the human gut
Gut microbes rely on nutrient exchange for survival, but these cross-feeding interactions remain poorly characterized. Here, Marcelino et al. present a metabolite-exchange scoring system derived from metagenome-scale metabolic models, designed to identify the potential microbial cross-feeding interactions most affected in human diseases.
- Vanessa R. Marcelino
- , Caitlin Welsh
- & Samuel C. Forster
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Article
| Open AccessEvolution of lasR mutants in polymorphic Pseudomonas aeruginosa populations facilitates chronic infection of the lung
Chronic infection with the bacterium Pseudomonas aeruginosa often leads to coexistence of heterogeneous bacterial populations carrying diverse mutations. Here, Zhao et al. use genetic and multi-omics functional analyses to shed light on the multistage evolution of bacterial populations in the lungs of chronically infected patients.
- Kelei Zhao
- , Xiting Yang
- & Xikun Zhou
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Article
| Open AccessEstimating the burden of severe malarial anaemia and access to hospital care in East Africa
Severe malarial anaemia is a clinical manifestation of severe malaria, with the burden highly concentrated in children. In this work, authors statistically model household survey and in-hospital data to estimate the proportion of severe malarial anaemia cases that access hospital care.
- Peter Winskill
- , Aggrey Dhabangi
- & Lucy C. Okell
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Article
| Open AccessGenomic dissection of endemic carbapenem resistance reveals metallo-beta-lactamase dissemination through clonal, plasmid and integron transfer
Resistance to carbapenems, a class of last-line antibiotics, is a global health threat. This study analysed a two-decade history of carbapenem resistance and identified complex, multi-level (bacterial strain, plasmid, gene) transmission dynamics.
- Nenad Macesic
- , Jane Hawkey
- & Anton Y. Peleg
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Article
| Open AccessGut microbiome dysbiosis across early Parkinson’s disease, REM sleep behavior disorder and their first-degree relatives
Microbiota-gut-brain axis may play an important role in Parkinson’s disease (PD). Here, the authors assess gut microbiota in early PD, REM sleep behaviour disorder (RBD) and first-degree relatives of RBD and show PD-like gut dysbiosis occurs in RBD and their first-degree relatives.
- Bei Huang
- , Steven W. H. Chau
- & Yun Kwok Wing
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Article
| Open AccessA point mutation in recC associated with subclonal replacement of carbapenem-resistant Klebsiella pneumoniae ST11 in China
Authors carry out a genomic analysis of carbapenem-resistant Klebsiella pneumoniae bloodstream isolates, noting subclonal expansion, associated with the emergence of a hypervirulent subpopulation.
- Kai Zhou
- , Chun-Xu Xue
- & Yonghong Xiao
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Article
| Open AccessThe evolution and international spread of extensively drug resistant Shigella sonnei
An increase in shigellosis cases among men who have sex with men in the United Kingdom has been linked to an extensively drug-resistant strain of Shigella sonnei. In this genomic epidemiology study, the authors investigate the genetic basis, evolutionary history, and international dissemination of the outbreak strain.
- Lewis C. E. Mason
- , David R. Greig
- & Kate S. Baker
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Article
| Open AccessClinical NEC prevention practices drive different microbiome profiles and functional responses in the preterm intestine
Here, the authors comparatively analyze the impact of three successful clinical preventive interventions against NEC in preterm, VLBW infants and demonstrate a major impact of especially probiotic-based strategies on the development and maturation of the gut microbiome.
- Charlotte J. Neumann
- , Alexander Mahnert
- & Christine Moissl-Eichinger
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Article
| Open AccessComparison of fecal and blood metabolome reveals inconsistent associations of the gut microbiota with cardiometabolic diseases
Here, analyzing paired fecal and blood metabolomics and metagenomics data in a large cohort, Deng et al. uncover disparate associations of the gut microbiota with cardiometabolic diseases when utilizing either fecal or blood metabolome data, suggesting that sampling criteria may be a relevant factor in metabolomics-based association studies.
- Kui Deng
- , Jin-jian Xu
- & Yu-ming Chen
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Article
| Open AccessCopper intrauterine device increases vaginal concentrations of inflammatory anaerobes and depletes lactobacilli compared to hormonal options in a randomized trial
Here, in a randomized trial, the authors comparatively evaluate the effect of a copper intrauterine device versus other contraceptive options on the vaginal environment after one and six consecutive months of use, finding to exert changes on the vaginal microbiota that may potentially lead to detrimental sex and reproductive health.
- Bryan P. Brown
- , Colin Feng
- & Heather B. Jaspan
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Article
| Open AccessRapid emergence of extensively drug-resistant Shigella sonnei in France
There have been increasing reports of extensively drug-resistant (XDR) Shigella sonnei infections in recent years. In this laboratory surveillance study from France, the authors document the rise of XDR isolates from 2005 to 2021 and perform whole genome sequencing to investigate their genomic diversity and evolutionary history.
- Sophie Lefèvre
- , Elisabeth Njamkepo
- & François-Xavier Weill
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Article
| Open AccessResolving colistin resistance and heteroresistance in Enterobacter species
Taxonomical complexity has muddled the classification of clinically relevant Enterobacter species. Authors carry out a genome-based study on clinical isolates to investigate colistin resistance and heteroresistance in Enterobacter.
- Swapnil Prakash Doijad
- , Nicolas Gisch
- & Trinad Chakraborty
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Article
| Open AccessAn ISO-certified genomics workflow for identification and surveillance of antimicrobial resistance
The implementation of genomics for identification and surveillance of antimicrobial resistance (AMR) in clinical laboratories remains challenging. Here, Sherry et al. present a bioinformatics platform for detection of AMR determinants from whole-genome sequencing data, suitable for clinical and public-health microbiology reporting.
- Norelle L. Sherry
- , Kristy A. Horan
- & Torsten Seemann
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Article
| Open AccessDynamic 18F-Pretomanid PET imaging in animal models of TB meningitis and human studies
Pretomanid has been approved for use in cases of multi-drug resistant pulmonary tuberculosis, yet the penetration of this antibiotic into other target tissues is not well established. Authors provide insight on pretomanid pharmacokinetics in the central nervous system, using positron emission tomography in animal models, and human studies.
- Filipa Mota
- , Camilo A. Ruiz-Bedoya
- & Sanjay K. Jain
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Article
| Open AccessStrong pathogen competition in neonatal gut colonisation
Opportunistic bacterial pathogen species frequently colonise the human gut as a normal part of the ecosystem but strain-level colonisation and competition dynamics in healthy hosts is yet to be established. Authors seek to understand the relationship between colonisation potential and ecological factors modulating pathogen prevalence in disease in a longitudinal cohort.
- Tommi Mäklin
- , Harry A. Thorpe
- & Jukka Corander
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Article
| Open AccessHost-dependent resistance of Group A Streptococcus to sulfamethoxazole mediated by a horizontally-acquired reduced folate transporter
There is increasing evidence for metabolic processes mediating antimicrobial resistance. Here, the authors present a mechanism of sulfamethoxazole resistance in Group A Streptococcus that is dependent on acquiring end products of the host folate biosynthesis pathway.
- M. Kalindu D. Rodrigo
- , Aarti Saiganesh
- & Timothy C. Barnett
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Article
| Open AccessMulti-kingdom gut microbiota analyses define COVID-19 severity and post-acute COVID-19 syndrome
Here, by performing an integrative multi-omics analysis coupled to clinical features of COVID-19 patients prospectively followed for up to 6 month, the authors identify specific gut microbiome patterns associated with disease severity and development of post-acute COVID-19 syndrome.
- Qin Liu
- , Qi Su
- & Siew C. Ng
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Review Article
| Open AccessThe importance of antimicrobial resistance in medical mycology
The impact of fungal infections on human health has been exacerbated by the rise of antifungal drug resistance. In this Review, the authors outline the problem of antifungal resistance and suggest how this growing threat might be mitigated.
- Neil A. R. Gow
- , Carolyn Johnson
- & Keegan Edgar
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Article
| Open AccessDissecting the role of the human microbiome in COVID-19 via metagenome-assembled genomes
Here, using whole-metagenome shotgun sequencing data from patients with COVID-19 and controls, the authors reconstruct 11,584 microbial metagenome-assembled genomes (MAGs) including 5,403 non-redundant MAGs, revealing microbiota and metabolic pathways associations with SARS-CoV-2 infection at strain-level resolution.
- Shanlin Ke
- , Scott T. Weiss
- & Yang-Yu Liu
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Article
| Open AccessA suite of PCR-LwCas13a assays for detection and genotyping of Treponema pallidum in clinical samples
Clinical diagnosis of Treponema pallidum subspecies pallidum (TPA), the causative agent of syphilis, depends upon serological testing, which has reduced sensitivity for some stages of the disease. Accompanying methods to complement serological testing also have distinct limitations. In this work, authors develop an assay that combines PCR with CRISPR-LwCas13a, and demonstrate sensitivity and specificity on clinically confirmed syphilis samples.
- Wentao Chen
- , Hao Luo
- & Heping Zheng
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Article
| Open AccessClinical characteristics and immune profile alterations in vaccinated individuals with breakthrough Delta SARS-CoV-2 infections
SARS-CoV-2 breakthrough infections in vaccinated individuals are a public health concern. Here, the authors analyse the clinical characteristics and profile immune alterations among vaccinated and non-vaccinated residents with Delta SARS-CoV-2 infection in Guangzhou.
- Qinghong Fan
- , Jingrong Shi
- & Feng Li
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Article
| Open AccessEngineering probiotics to inhibit Clostridioides difficile infection by dynamic regulation of intestinal metabolism
Clostridioides difficile infection (CDI) results in significant morbidity and mortality in hospitalised patients. Here the authors engineer probiotics to restore intestinal bile salt metabolism in response to antibiotic-induced microbiome dysbiosis significantly inhibit Clostridioides difficile infection in model mice, presenting a microbiome-based antimicrobial strategy
- Elvin Koh
- , In Young Hwang
- & Matthew Wook Chang
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Article
| Open AccessComparative genomics of Acinetobacter baumannii and therapeutic bacteriophages from a patient undergoing phage therapy
A patient with a multidrug-resistant bacterial infection was successfully treated in 2016 using phage therapy. Here, the authors sequence the genomes of the therapeutic phages and three bacterial strains isolated before and during treatment, and show that the same mutations conferring phage resistance are found in in vitro-generated mutants and in phage-insensitive strains isolated from the patient.
- Mei Liu
- , Adriana Hernandez-Morales
- & Jason J. Gill
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Article
| Open AccessGenomic dissection of Klebsiella pneumoniae infections in hospital patients reveals insights into an opportunistic pathogen
Klebsiella pneumoniae is an opportunistic pathogen of increasing public health concern due to the prevalence of antimicrobial resistance. Here, the authors provide insight into the resistance profiles, bacterial genome features and virulence genes, in a year-long prospective study of K. pneumoniae clinical isolates.
- Claire L. Gorrie
- , Mirjana Mirčeta
- & Kathryn E. Holt
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Article
| Open AccessMetabolic preference assay for rapid diagnosis of bloodstream infections
It is currently slow to identify bloodstream infection pathogens. Here the authors report a rapid metabolic preference assay that uses the pattern of metabolic fluxes observed in ex-vivo microbial cultures to identify common pathogens and determine their antimicrobial susceptibility profiles.
- Thomas Rydzak
- , Ryan A. Groves
- & Ian A. Lewis
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Article
| Open AccessAssessment of global health risk of antibiotic resistance genes
Antibiotic resistance genes (ARGs) have accelerated microbial threats to human health. Here, Zhang et al. analyze 4572 metagenomic samples to illustrate the global patterns of ARG distribution in diverse habitats. They quantitatively evaluate the health risk to humans of 2561 ARGs by integrating human accessibility, mobility, pathogenicity and clinical availability. With the machine learning, they map the antibiotic resistance threats in global marine habitats.
- Zhenyan Zhang
- , Qi Zhang
- & Haifeng Qian
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Article
| Open AccessDifferent gut microbial communities correlate with efficacy of albendazole-ivermectin against soil-transmitted helminthiases
Little is known about the cause of treatment failure of soil-transmitted helminth infections. Here, the authors show that pre-treatment gut microbial community composition enables predicting treatment outcome for Trichuris trichiura and hookworm infections.
- Pierre H. H. Schneeberger
- , Morgan Gueuning
- & Jennifer Keiser
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Article
| Open AccessNeutralization against Omicron SARS-CoV-2 from previous non-Omicron infection
The SARS-CoV-2 variant of concern Omicron has quickly spread. Here, Zou et al. develop a high-throughput neutralization test for Omicron SARS-CoV-2 and show that patients with previous non-Omicron infections do not develop robust neutralization against Omicron.
- Jing Zou
- , Hongjie Xia
- & Pei-Yong Shi
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Article
| Open AccessRare transmission of commensal and pathogenic bacteria in the gut microbiome of hospitalized adults
Here, Siranosian et al. provide evidence for rare transmission of commensal and pathogenic bacteria between the microbiomes of hospitalized adults, with important factors being roommate overlap and exposure to broad-spectrum antibiotics.
- Benjamin A. Siranosian
- , Erin F. Brooks
- & Ami S. Bhatt
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Article
| Open AccessCombination of pre-adapted bacteriophage therapy and antibiotics for treatment of fracture-related infection due to pandrug-resistant Klebsiella pneumoniae
In this case study of a patient with fracture-related pandrug-resistant Klebsiella pneumoniae infection after long-term antibiotic therapy, the authors use a combination therapy of pre-adapted bacteriophage and antibiotics resulting in clinical, microbiological and radiological improvement.
- Anaïs Eskenazi
- , Cédric Lood
- & Jean-Paul Pirnay
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Article
| Open AccessPlasma virome and the risk of blood-borne infection in persons with substance use disorder
Spread of bloodborne infections, such as HCV and HIV, is a problem, particularly amongst people who inject drugs (PWID). Here, the authors describe and then confirm in observational PWID cohorts that those with more non-pathogenic viruses in plasma were more likely later to acquire HCV than PWID who had fewer of these non-pathogenic viruses.
- Abraham J. Kandathil
- , Andrea L. Cox
- & David L. Thomas
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Article
| Open AccessOrgan-specific genome diversity of replication-competent SARS-CoV-2
Here the authors provide a detailed virological analysis of thirteen postmortem COVID-19 cases, including presence of replication-competent SARS-CoV-2 in extrapulmonary organs and tissue-specific patterns of SARS-CoV-2 genome diversity of an immunocompromised patient.
- Jolien Van Cleemput
- , Willem van Snippenberg
- & Linos Vandekerckhove
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Article
| Open AccessClinical practices underlie COVID-19 patient respiratory microbiome composition and its interactions with the host
Here, the authors profile the respiratory microbiome of COVID-19 patients and link clinical practices, such as mechanical ventilation, with vast changes in the microbiota. In the lungs, oral bacteria are found physically associated with proinflammatory immune cells, thus possibly contributing to exacerbated immune responses in severe disease
- Verónica Lloréns-Rico
- , Ann C. Gregory
- & Jeroen Raes
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Article
| Open AccessSpecific gut microbiome signatures and the associated pro-inflamatory functions are linked to pediatric allergy and acquisition of immune tolerance
Here, the authors profile the taxonomic composition and genetic potential of the gut microbiome of children with food or respiratory allergies and find that the gut metagenome of these patients is characterized by higher proinflammatory potential and reduced capacity of degrading complex polysaccharides, with Ruminococcus gnavus playing a central role.
- Francesca De Filippis
- , Lorella Paparo
- & Roberto Berni Canani