Featured
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| Open AccessIdentification of microbial markers across populations in early detection of colorectal cancer
The gut microbiome plays an important role in colorectal carcinogenesis and predictive microbiome signatures have been proposed for colorectal cancer (CRC) diagnosis. Here the authors perform a meta-analysis of 16S rRNA-based profiles to identify microbial markers able to discriminate patients with adenoma from control and CRC, building a model that can be applied for the early detection of CRC.
- Yuanqi Wu
- , Na Jiao
- & Lixin Zhu
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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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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 AccessPrimary and secondary clarithromycin resistance in Helicobacter pylori and mathematical modeling of the role of macrolides
Clarithromycin is a macrolide antibiotic widely used for eradication of Helicobacter pylori infection. Here, Kocsmár et al. study clarithromycin resistance and previous macrolide consumption in 4,744 H. pylori-infected patients, shedding light into the sources of primary resistant cases and the role played by prior consumption of macrolides for non-eradication purposes.
- Éva Kocsmár
- , György Miklós Buzás
- & Gábor Lotz
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Article
| Open AccessA bacterial small RNA regulates the adaptation of Helicobacter pylori to the host environment
Long-term infection of the stomach with Helicobacter pylori can cause gastric cancer. Here, Kinoshita-Daitoku et al. show that a small non-coding RNA of H. pylori regulates bacterial adaptation to the stomach environment and bacterial oncoprotein production.
- Ryo Kinoshita-Daitoku
- , Kotaro Kiga
- & Hitomi Mimuro
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Article
| Open AccessHigh-throughput fitness screening and transcriptomics identify a role for a type IV secretion system in the pathogenesis of Crohn’s disease-associated Escherichia coli
Adherent-invasive E. coli (AIEC) are frequently isolated from Crohn’s disease (CD) patients. Here, Elhenawy et al. conduct a genome-wide screen to identify AIEC genes required for in vivo intestinal colonization, and show that a type IV secretion system contributes to AIEC persistence in the gut and is enriched in CD patients’ isolates.
- Wael Elhenawy
- , Sarah Hordienko
- & Brian K. Coombes
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Article
| Open AccessNonlinear machine learning pattern recognition and bacteria-metabolite multilayer network analysis of perturbed gastric microbiome
Drug use or bacterial infection can cause significant alterations of gastric microbiome. Here, the authors show how advanced pattern recognition by nonlinear machine intelligence can help disclose a bacteria-metabolite network which enlightens mechanisms behind such perturbations.
- Claudio Durán
- , Sara Ciucci
- & Carlo Vittorio Cannistraci
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Article
| Open AccessBiofilm formation in the lung contributes to virulence and drug tolerance of Mycobacterium tuberculosis
Mycobacterium tuberculosis forms biofilms in vitro, but it is unclear whether biofilms are also formed during infection in vivo. Here, Chakraborty et al. demonstrate the formation of biofilms in animal models of infection and in patients with tuberculosis, and that biofilm formation can contribute to drug tolerance.
- Poushali Chakraborty
- , Sapna Bajeli
- & Ashwani Kumar
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Article
| Open AccessGastrointestinal microbiota composition predicts peripheral inflammatory state during treatment of human tuberculosis
Antibiotic therapy can lead to pathogen clearance, but also to alterations in the gut microbiota and systemic immune responses. Here, the authors analyze data from patients with tuberculosis and healthy subjects to show that pathogen clearance and gut microbiota alterations are independently associated with antibiotic-induced changes of the inflammatory response of active tuberculosis.
- Matthew F. Wipperman
- , Shakti K. Bhattarai
- & Vanni Bucci
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Article
| Open AccessIL-22-dependent dysbiosis and mononuclear phagocyte depletion contribute to steroid-resistant gut graft-versus-host disease in mice
Pathogenesis of steroid-resistant gut acute graft-versus-host-disease (SR-Gut-aGVHD) remains unclear., Here the authors show in mouse models that dysbiosis caused by the expansion of Th/Tc22, as well as depletion of CX3CR1hi mononuclear phagocytes resulted from the reduction of Th/Tc1, contributes to SR-Gut-aGVHD onset.
- Qingxiao Song
- , Xiaoning Wang
- & Defu Zeng
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Article
| Open AccessA Sarcina bacterium linked to lethal disease in sanctuary chimpanzees in Sierra Leone
Infections with bacteria of the genus Sarcina are associated with gastric diseases of unclear etiology. Here, Owens et al. show that infection with a distinct Sarcina species is strongly associated with a lethal disease that affects sanctuary chimpanzees in Sierra Leone.
- Leah A. Owens
- , Barbara Colitti
- & Tony L. Goldberg
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Article
| Open AccessUbiquitous selection for mecA in community-associated MRSA across diverse chemical environments
The mecA gene confers resistance to many β-lactam antibiotics in community-associated MRSA bacteria. Here, Snitser et al. show that mecA also provides broad selective advantage across diverse chemical environments in the presence of subinhibitory β-lactam concentrations, by protecting the bacteria against increased cell-envelope permeability.
- Olga Snitser
- , Dor Russ
- & Roy Kishony
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Article
| Open AccessHorizontally acquired papGII-containing pathogenicity islands underlie the emergence of invasive uropathogenic Escherichia coli lineages
Escherichia coli is a major cause of urinary tract infection. Here, Biggel et al. provide a phylogenomic analysis of 907 clinical E. coli isolates and identify the P-fimbriae-encoding locus associated with invasive uropathogenic E. coli isolates.
- Michael Biggel
- , Basil B. Xavier
- & Sandra Van Puyvelde
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Article
| Open AccessThe seventh pandemic of cholera in Europe revisited by microbial genomics
Since 1970, several cholera outbreaks caused by the “seventh pandemic” (7PET) lineage have been reported in Europe. Here, the authors demonstrate that the outbreaks were caused by repeated introductions of 7PET into Europe, rather than local environmental sources.
- Mihaela Oprea
- , Elisabeth Njamkepo
- & François-Xavier Weill
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Article
| Open AccessPiperacillin/tazobactam resistance in a clinical isolate of Escherichia coli due to IS26-mediated amplification of blaTEM-1B
An E. coli and K. pneumoniae phenotype resistant to piperacillin/tazobactam has recently emerged. Here, the authors show that hyperproduction of the β-lactamase driving this resistance occurs due to excision and reinsertion of a translocatable unit containing blaTEM-1B, creating a tandem array.
- Alasdair T. M. Hubbard
- , Jenifer Mason
- & Thomas Edwards
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Article
| Open AccessWithin-host microevolution of Streptococcus pneumoniae is rapid and adaptive during natural colonisation
Streptococcus pneumoniae is an opportunistic pathogen and asymptomatic colonization is a precursor for invasive disease. Here the authors show rapid within-host evolution of naturally acquired pneumococci in ninety-eight infants driven by high nucleotide substitution rates and intra-host homologous recombination.
- Chrispin Chaguza
- , Madikay Senghore
- & Brenda A. Kwambana-Adams
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Article
| Open AccessAn ecological framework to understand the efficacy of fecal microbiota transplantation
Here, the authors present a theoretical framework based on community ecology and network science to investigate the efficacy of fecal microbiota transplantation in conditions associated with a disrupted gut microbiota, using the recurrent Clostridioides difficile infection as a prototype disease.
- Yandong Xiao
- , Marco Tulio Angulo
- & Yang-Yu Liu
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Article
| Open AccessDevelopment of CRISPR-Cas13a-based antimicrobials capable of sequence-specific killing of target bacteria
CRISPR technology is emerging as a potential antimicrobial against antimicrobial-resistant bacteria. Here the authors develop a bacteriophage delivered Cas13a system for killing target bacteria and detecting bacterial genes.
- Kotaro Kiga
- , Xin-Ee Tan
- & Longzhu Cui
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Article
| Open AccessA randomized trial evaluating virus-specific effects of a combination probiotic in children with acute gastroenteritis
Here, the authors report the results of a randomized, placebo controlled trial of children with acute gastroenteritis who were treated with a probiotic and find no virus-specific beneficial effects attributable to the probiotic, either in reducing clinical symptoms or clearance of viral nucleic acid from stool specimens.
- Stephen B. Freedman
- , Jianling Xie
- & Marc H. Gorelick
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Article
| Open AccessIntegrating multiple genomic technologies to investigate an outbreak of carbapenemase-producing Enterobacter hormaechei
Antibiotic-resistant bacteria are an urgent threat to human health. Here, Roberts et al. characterise and monitor an ongoing hospital outbreak of carbapenemase-producing Enterobacter hormaechei by integrating several technologies for whole-genome sequencing and shotgun metagenomics.
- Leah W. Roberts
- , Patrick N. A. Harris
- & Scott A. Beatson
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Article
| Open AccessAcquisition, transmission and strain diversity of human gut-colonizing crAss-like phages
CrAss-like phages are bacterial viruses often found in the human gut. Here, Siranosian et al. analyze gut metagenomic data to evaluate the patterns of acquisition, transmission and strain diversity of these phages in mother-infant pairs and in patients undergoing fecal microbiota transplantation.
- Benjamin A. Siranosian
- , Fiona B. Tamburini
- & Ami S. Bhatt
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Article
| Open AccessRapid identification of pathogenic bacteria using Raman spectroscopy and deep learning
The use of Raman spectroscopy for pathogen identification is hampered by the weak Raman signal and phenotypic diversity of bacterial cells. Here the authors generate an extensive dataset of bacterial Raman spectra and apply deep learning to identify common bacterial pathogens and predict antibiotic treatment from noisy Raman spectra.
- Chi-Sing Ho
- , Neal Jean
- & Jennifer Dionne
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Article
| Open AccessSpatiotemporal dynamics of multidrug resistant bacteria on intensive care unit surfaces
The authors investigate the burden and spatiotemporal dynamics of multidrug-resistant bacteria on intensive care unit surfaces from two hospitals in the US and Pakistan over a year. They find Acinetobacter baumannii and Enterococcus faecium co-association, likely due to synergistic biofilm formation.
- Alaric W. D’Souza
- , Robert F. Potter
- & Gautam Dantas
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Article
| Open AccessPossible role of L-form switching in recurrent urinary tract infection
The reservoir for recurrent urinary tract infection in humans is unclear. Here, Mickiewicz et al. detect cell-wall deficient (L-form) E. coli in fresh urine from patients, and show that the isolated bacteria readily switch between walled and L-form states.
- Katarzyna M. Mickiewicz
- , Yoshikazu Kawai
- & Jeff Errington
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Article
| Open AccessOmpK36-mediated Carbapenem resistance attenuates ST258 Klebsiella pneumoniae in vivo
Carbapenem-resistance in Klebsiella pneumoniae sequence type ST258 can be enhanced by modification of the porins OmpK35 and OmpK36. Here, Wong et al. solve the crystal structure of a clinical ST258 OmpK36 variant, elucidating the mechanism of resistance and consequences on pathogenicity in vivo.
- Joshua L. C. Wong
- , Maria Romano
- & Gad Frankel
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Article
| Open AccessMolecular profiling of tissue biopsies reveals unique signatures associated with streptococcal necrotizing soft tissue infections
Necrotizing soft tissue infections (NSTIs) are caused by a single pathogen such as Streptococcus pyogenes or by multiple bacterial species. Here, the authors integrate microbial community profiling with host and pathogen transcriptional analysis in patient biopsies, and identify an interferon-related signature specific to S. pyogenes NSTIs.
- Robert Thänert
- , Andreas Itzek
- & Dietmar H. Pieper
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Article
| Open AccessPopulation dynamics of an Escherichia coli ST131 lineage during recurrent urinary tract infection
Recurrent urinary tract infections occur in ~ 25% of women. Here, Beatson and colleagues use whole genome sequencing to track the dynamics of an E. coli ST131 clone in a single patient over a 5-year period. This study provides unique insights into pathogen evolution during recurrent urinary infection.
- Brian M. Forde
- , Leah W. Roberts
- & Scott A. Beatson
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Article
| Open AccessGenetically diverse Pseudomonas aeruginosa populations display similar transcriptomic profiles in a cystic fibrosis explanted lung
Pseudomonas aeruginosa displays substantial genetic diversification across sub-compartments in cystic fibrosis (CF) lungs. Here, Kordes et al. show that, despite genetic variation, the ex vivo transcriptional profiles of P. aeruginosa populations are similar across five different areas in an explanted CF lung.
- Adrian Kordes
- , Matthias Preusse
- & Susanne Häussler
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Article
| Open AccessSchistosoma mansoni treatment reduces HIV entry into cervical CD4+ T cells and induces IFN-I pathways
Schistosoma mansoniinfection has been linked with an increased risk of HIV acquisition in women. Here, the authors show that standard S. mansoniinfection treatment causes a reduction of HIV entry into cervical and blood CD4+ T cells, which is sustained for up to two months and is associated with de-repression of IFN-I signaling.
- Sergey Yegorov
- , Vineet Joag
- & Rupert Kaul
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Article
| Open AccessAltered respiratory virome and serum cytokine profile associated with recurrent respiratory tract infections in children
Here, the authors determine the respiratory virome and serum cytokine profile in children diagnosed with acute respiratory tract infections (ARTI) and show that relative abundance of Propionibacterium phages as well as serum levels of TIMP-1 and PDGF-BB are increased in multiple ARTIs compared with single ARTI.
- Yanpeng Li
- , Xuemin Fu
- & Chiyu Zhang
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Article
| Open AccessSmall intestinal microbial dysbiosis underlies symptoms associated with functional gastrointestinal disorders
Small intestinal bacterial overgrowth (SIBO) has been associated with functional gastrointestinal disorders. Here, the authors show that SIBO may be a result of dietary preferences, and patient symptoms correlate with changes in small intestinal microbial composition but not with SIBO.
- George B. Saffouri
- , Robin R. Shields-Cutler
- & Purna C. Kashyap
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Article
| Open AccessA defined mechanistic correlate of protection against Plasmodium falciparum malaria in non-human primates
Proof of protection against blood-stage P. falciparum malaria by a single immunological mechanism has been elusive. Here, using engineered anti-PfRH5 chimeric monoclonal antibodies in non-human primates, the authors show that high levels of merozoite-neutralizing antibodies can achieve protection.
- Alexander D. Douglas
- , G. Christian Baldeviano
- & Simon J. Draper
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Article
| Open AccessIn-host evolution of Staphylococcus epidermidis in a pacemaker-associated endocarditis resulting in increased antibiotic tolerance
Staphylococcus epidermidis is a frequent cause of medical implant-associated biofilm infections. Here, studying a patient with pacemaker-associated endocarditis, the authors report in-host evolution of S. epidermidis leading to phenotypes exhibiting increased biofilm formation and antibiotic tolerance.
- Vanina Dengler Haunreiter
- , Mathilde Boumasmoud
- & Annelies S. Zinkernagel
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Article
| Open AccessA diversity-oriented rhodamine library for wide-spectrum bactericidal agents with low inducible resistance against resistant pathogens
Preparation of xanthene-containing compounds has been limited due to structural bias existing methods pose. Here, the authors developed a mild, diversity-oriented method for rhodamines synthesis, leading to the finding of compounds with antibacterial potency against a variety of bacterial species.
- Xiao Luo
- , Liujia Qian
- & Youjun Yang
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Article
| Open AccessMicrobiota-driven interleukin-17-producing cells and eosinophils synergize to accelerate multiple myeloma progression
The mechanisms through which gut microbiota affect extramucosal tumors are poorly understood. Here the authors show that the gut microbiota promotes multiple myeloma by inducing differentiation and migration of Th17 cells in the bone marrow resulting also in increased recruitment of pro-tumorigenic eosinophils.
- Arianna Calcinotto
- , Arianna Brevi
- & Matteo Bellone
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Article
| Open AccessMeta-analysis of effects of exclusive breastfeeding on infant gut microbiota across populations
Studies on the effects of breastfeeding on the infant gut microbiota have provided inconsistent results. Here, Ho et al. perform a meta-analysis of seven studies across different populations, supporting that exclusive breastfeeding is associated with short-term and long-term alterations in the infant gut microbiota.
- Nhan T. Ho
- , Fan Li
- & Louise Kuhn
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Article
| Open AccessProlonged bacterial lag time results in small colony variants that represent a sub-population of persisters
Persisters are bacterial subpopulations that are not killed by antibiotics even though they lack genetic resistance. Here, the authors show that persisters can manifest as small colony variants in clinical infections, and arise as a result of a long lag time in stress conditions including antibiotic exposure.
- Clément Vulin
- , Nadja Leimer
- & Annelies S. Zinkernagel
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Article
| Open AccessLung colonization by Aspergillus fumigatus is controlled by ZNF77
Aspergillus fumigatus regularly colonises the lungs but in the context of respiratory disease can be associated with increased pathology. Here the authors show mutations in ZNF77 result in altered bronchial epithelial characteristics and enhanced fungal burden.
- Sara Gago
- , Nicola L. D. Overton
- & Paul Bowyer
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Article
| Open AccessA spatial gradient of bacterial diversity in the human oral cavity shaped by salivary flow
Oral microbial communities are excellent sites for examining the mechanisms of structural variation in the microbiota. Here, the authors use spatial and ecological analysis to examine over 9000 dental and mucosal microbiota samples. They find that saliva plays a key role in structuring bacterial communities in the mouth.
- Diana M. Proctor
- , Julia A. Fukuyama
- & David A. Relman
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Article
| Open AccessPhylogenomics and antimicrobial resistance of the leprosy bacillus Mycobacterium leprae
Leprosy is caused by the yet-uncultured pathogen Mycobacterium leprae. Here, Benjak et al. obtain M. leprae genome sequences from DNA extracted from patients' skin biopsies and, by analysing 154 genomes from 25 countries, provide insight into the pathogen’s evolution and antimicrobial resistance.
- Andrej Benjak
- , Charlotte Avanzi
- & Stewart T. Cole
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Article
| Open AccessImmune stealth-driven O2 serotype prevalence and potential for therapeutic antibodies against multidrug resistant Klebsiella pneumoniae
Therapeutics to combat multidrug-resistant bacteria such as Klebsiella pneumoniae are needed. Here the authors show immune evasion drives lipopolysaccharide O2 serotype expansion in multidrug-resistant isolates, and anti-O-antigen human monoclonal antibodies synergize with antibiotics to protect mice from infection.
- Meghan E. Pennini
- , Anna De Marco
- & C. Kendall Stover
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Article
| Open AccessTransmission-blocking interventions eliminate malaria from laboratory populations
Transmission-blocking interventions aim to interrupt progression of Plasmodium parasites from the vertebrate host to the mosquito. Blagborough et al. demonstrate that only partially reducing transmission can be sufficient to eliminate experimental Plasmodiuminfection in successive mosquito and mice populations when biting rates are low.
- A. M. Blagborough
- , T. S. Churcher
- & R. E. Sinden