Featured
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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
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Article
| Open AccessDistinct clinical and immunological profiles of patients with evidence of SARS-CoV-2 infection in sub-Saharan Africa
Clinical management of COVID-19 in resource-poor settings has distinct challenges and detailed patient characterisation is needed. Here, the authors describe the clinical and immunological profiles of patients at a hospital in Malawi with confirmed and suspected COVID-19.
- Ben Morton
- , Kayla G. Barnes
- & Kondwani C. Jambo
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Article
| 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