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| 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 AccessDistributed genotyping and clustering of Neisseria strains reveal continual emergence of epidemic meningococcus over a century
Core genome multilocus sequence typing (cgMLST) is used to classify bacterial strains for epidemiological applications. Here, the authors describe a distributed cgMLST scheme that does not require a central database of allelic sequences, and apply it to study evolutionary patterns of epidemic and endemic strains of the genus Neisseria.
- Ling Zhong
- , Menghan Zhang
- & Zhemin Zhou
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Article
| Open AccessRegulation of the physiology and virulence of Ralstonia solanacearum by the second messenger 2′,3′-cyclic guanosine monophosphate
Nucleotide second messengers are employed by many bacterial species to regulate various cellular processes. Here, the authors demonstrate that 2',3'-cyclic guanosine monophosphate (2',3'-cGMP) controls the important biological functions and virulence in Ralstonia solanacearum by abolishing the interaction between a transcriptional regulator and the promoters of target genes.
- Xia Li
- , Wenfang Yin
- & Yinyue Deng
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Article
| Open AccessA smooth tubercle bacillus from Ethiopia phylogenetically close to the Mycobacterium tuberculosis complex
The Mycobacterium tuberculosis complex (MTBC) includes several pathogens thought to have originated in East Africa from an ancestor closely related to Mycobacterium canettii. Here, the authors describe a clinical tuberculosis strain isolated in Ethiopia that has typical M. canettii features but is phylogenetically much closer to the MTBC clade, supporting that the emergence of MTBC pathogens is a recent evolutionary event.
- Bazezew Yenew
- , Arash Ghodousi
- & Daniela Maria Cirillo
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Article
| Open Accessc-di-GMP inhibits the DNA binding activity of H-NS in Salmonella
H-NS is a global regulatory protein that represses expression of many genes in bacteria. Here, Li et al. show that a second messenger, cyclic di-GMP, binds to H-NS and inhibits its binding to DNA, thus relieving H-NS-mediated transcriptional silencing.
- Shuyu Li
- , Qinmeng Liu
- & Lei Zhang
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Article
| Open AccessSynthetic genetic oscillators demonstrate the functional importance of phenotypic variation in pneumococcal-host interactions
Here, Rueff et al engineered a CRISPRi-based oscillator to rewire capsule production in Streptococcus pneumoniae from its native control. They show that heterogeneity in capsule production is beneficial for fitness in several virulence associated traits.
- Anne-Stéphanie Rueff
- , Renske van Raaphorst
- & Jan-Willem Veening
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Article
| Open AccessGlutamine metabolism inhibition has dual immunomodulatory and antibacterial activities against Mycobacterium tuberculosis
Parveen et al., using immunological, and metabolomics-based assays, demonstrate the importance of host glutamine metabolism in tuberculosis pathogenesis and show host-directed activity against tuberculosis.
- Sadiya Parveen
- , Jessica Shen
- & William R. Bishai
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Article
| Open AccessEnterohaemorrhagic E. coli utilizes host- and microbiota-derived L-malate as a signaling molecule for intestinal colonization
Here, Liu et al show that enterohaemorrhagic Escherichia coli utilizes host- and microbiota-derived L-malate as an essential nutrient and signalling molecule to promote its growth and colonization in the large intestine.
- Bin Liu
- , Lingyan Jiang
- & Bin Yang
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Article
| Open AccessMutational spectra are associated with bacterial niche
Mutagens and DNA repair defects generate context-specific mutational signatures in cancer cells. Here, Ruis et al. provide evidence of similar processes in bacteria, showing that mutational spectra may be associated with sites of bacterial replication when mutagen exposures differ, and can be used in these cases to infer transmission routes.
- Christopher Ruis
- , Aaron Weimann
- & Julian Parkhill
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Article
| Open AccessInferring bacterial transmission dynamics using deep sequencing genomic surveillance data
Studying rare genetic changes that arose as an infectious bacterium spread between lab mice, here the authors show that using the relative abundance of any changes rather than just whether they occurred can more precisely identify who likely infected who.
- Madikay Senghore
- , Hannah Read
- & Siouxsie Wiles
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Article
| Open AccessThe structure of a hibernating ribosome in a Lyme disease pathogen
Ribosomes are prime targets for antibiotics in pathogenic bacteria. Here, cryo-electron microscopy reveals features in the Borrelia burgdorferi ribosome that provide insights into ribosome evolution, dormancy, and antibiotic binding.
- Manjuli R. Sharma
- , Swati R. Manjari
- & Nilesh K. Banavali
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Article
| Open AccessOrigin of fungal hybrids with pathogenic potential from warm seawater environments
Most clinical isolates of the pathogenic yeast Candida orthopsilosis are hybrids of two parental lineages, only one of which has been identified. Here, del Olmo et al. show that C. orthopsilosis strains isolated from warm seawater are hybrids closely related to clinical isolates, and identify the missing parental lineage, thus providing a more complete view of the genomic evolution of this species.
- Valentina del Olmo
- , Verónica Mixão
- & Toni Gabaldón
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Article
| Open AccessSystematic review and integrated data analysis reveal diverse pangolin-associated microbes with infection potential
The diversity and spillover potential of pangolin-associated microbes are not fully understood. Here, the authors describe the distribution and spectrum of reported pangolin microbes by integrating data from multiple sources and assess their potential to emerge as human pathogens.
- Run-Ze Ye
- , Xiao-Yang Wang
- & Wu-Chun Cao
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Article
| Open AccessProfiling of the Helicobacter pylori redox switch HP1021 regulon using a multi-omics approach
Helicobacter pylori adapted to the harsh conditions of the human stomach using a handful of regulatory proteins. Here, the authors identify H. pylori processes controlled by the HP1021 response regulator under optimal growth and oxidative stress.
- Mateusz Noszka
- , Agnieszka Strzałka
- & Anna Zawilak-Pawlik
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Article
| Open AccessA transcriptional activator effector of Ustilago maydis regulates hyperplasia in maize during pathogen-induced tumor formation
Ustilago maydis causes tumor on maize seedlings. Here we show that U. maydis secrets the transcriptional activator effector Sts2 to induce leaf developmental regulators which activate the bundle sheath cell division for tumor formation.
- Weiliang Zuo
- , Jasper R. L. Depotter
- & Gunther Doehlemann
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Article
| Open AccessStaphylococcus aureus sacculus mediates activities of M23 hydrolases
In this work, the authors provide structural insights into the interaction of two evolutionarily related peptidoglycan hydrolases, lysostaphin and LytM with S. aureus sacculus, and propose a model in which PG crosslinking affects their activity differently.
- Alicja Razew
- , Cedric Laguri
- & Jean-Pierre Simorre
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Article
| Open AccessStructural basis for the unique molecular properties of broad-range phospholipase C from Listeria monocytogenes
The bacterium Listeria monocytogenes possesses two major virulence factors, broad-range phospholipase C (LmPC-PLC) and the pore-forming toxin listeriolysin O (LLO). Here, authors perform structural and biochemical analysis of LmPC-PLC and show that unique structural features enable self-regulation of its enzymatic activity and positive synergy with the pore-forming toxin listeriolysin O.
- Nejc Petrišič
- , Maksimiljan Adamek
- & Marjetka Podobnik
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Article
| Open AccessHIV-1 treatment timing shapes the human intestinal memory B-cell repertoire to commensal bacteria
HIV-1 infection is known to impact the gut mucosa, effecting the microbiota and immune system, but early antiretroviral therapy is linked to partial reversal of this phenomena. Here the authors explore the impact of early commencement of antiretroviral therapy and show this can limit the abnormal responses of intestinal B cells associated with HIV-1 infection.
- Cyril Planchais
- , Luis M. Molinos-Albert
- & Hugo Mouquet
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Article
| Open AccessNAD+ metabolism is a key modulator of bacterial respiratory epithelial infections
Streptococcus pneumoniae is a common cause of lower respiratory tract infection. Here, Klabunde et al. present a transcriptomic, metabolomic and proteomic characterisation of the bronchial epithelial cell response to infection and show that NAD+ has a role in controlling bacterial replication.
- Björn Klabunde
- , André Wesener
- & Bernd Schmeck
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Article
| Open AccessAlphaFold-Multimer predicts cross-kingdom interactions at the plant-pathogen interface
AlphaFold-Multimer was used to screen of 1,879 small secreted proteins from plant pathogens to be inhibitors of six tomato defense enzymes. Four of these inhibit subtilase P69B, showing the use of AI to predict cross-kingdom protein interactions.
- Felix Homma
- , Jie Huang
- & Renier A. L. van der Hoorn
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Article
| Open AccessUstilago maydis PR-1-like protein has evolved two distinct domains for dual virulence activities
Plant PR-1 proteins participate in defense responses against pathogens. Here, the authors show that PR-1-like proteins from the plant pathogenic fungus Ustilago maydis are important for virulence by detecting plant-derived phenolics and modulating plant PR-1-mediated defenses.
- Yu-Han Lin
- , Meng-Yun Xu
- & Lay-Sun Ma
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Article
| Open AccessHigh-efficiency green management of potato late blight by a self-assembled multicomponent nano-bioprotectant
Unlike the other plant pathogens, Phytophtora infestans, the causative pathogen of potato late blight, can hardly take up dsRNA, which is a key obstacle in using dsRNA for disease control. Here, the authors design a self-assembled multicomponent nano-bioprotectant for potato late blight management.
- Yuxi Wang
- , Mingshan Li
- & Xiaodan Wang
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Article
| Open AccessPanoramic analysis of coronaviruses carried by representative bat species in Southern China to better understand the coronavirus sphere
In this study, Han, Xu, and Wang et al. probe the diversity of bat coronaviruses (CoVs), revealing their evolutionary pattern with hosts. It underscores the evolutionary processes of CoVs, including SARS-CoV-2, and emphasizes the urgency of ongoing bat CoV surveillance.
- Yelin Han
- , Panpan Xu
- & Zhiqiang Wu
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Article
| Open AccessPlant immunity suppression by an exo-β-1,3-glucanase and an elongation factor 1α of the rice blast fungus
Fungal cell walls release β-1,3-glucan fragments that trigger plant immunity. Here, the authors show that a glucanase (Ebg1) of the blast fungus Magnaporthe oryzae suppresses plant immunity by hydrolyzing β-1,3-glucan. At the same time, Ebg1 induces plant immune responses that are dampened by a fungal protein that interacts with Ebg1.
- Hang Liu
- , Xunli Lu
- & You-Liang Peng
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Article
| Open AccessA fungal sesquiterpene biosynthesis gene cluster critical for mutualist-pathogen transition in Colletotrichum tofieldiae
Plant-associated fungi range from pathogens to mutualists. Here the authors identify a gene cluster in a Colletotrichum tofieldiae strain that is required to allow the fungus to transition from a mutualist to a pathogen depending on the nutritional status of the host.
- Kei Hiruma
- , Seishiro Aoki
- & Yusuke Saijo
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Article
| Open AccessAncient Clostridium DNA and variants of tetanus neurotoxins associated with human archaeological remains
The analysis of microbial genomes from human archaeological samples offers a snapshot of ancient pathogens. Here, Hodgins et al. analyze metagenomic datasets from 38 human archaeological samples and identify bacterial genomic sequences related to modern-day Clostridium tetani, encoding tetanus neurotoxins.
- Harold P. Hodgins
- , Pengsheng Chen
- & Andrew C. Doxey
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Article
| Open AccessNAD(H) homeostasis underlies host protection mediated by glycolytic myeloid cells in tuberculosis
Mycobacterium tuberculosis disrupts glycolysis in infected myeloid cells. Here, Pacl et al. show that maximal glycolytic capacity in myeloid cells is essential for host protection from tuberculosis and that NAD(H) homeostasis underlies glycolysis-mediated protection of the host.
- Hayden T. Pacl
- , Krishna C. Chinta
- & Adrie J. C. Steyn
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Article
| Open AccessMetallo-sideromycin as a dual functional complex for combating antimicrobial resistance
Here, the authors utilise cefiderocol, a sideromycin, in complex with colloidal bismuth citrate, to demonstrate antimicrobial efficacy against Pseudomonas aeruginosa in vivo.
- Chenyuan Wang
- , Yushan Xia
- & Hongzhe Sun
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Article
| Open AccessAntibiotics promote intestinal growth of carbapenem-resistant Enterobacteriaceae by enriching nutrients and depleting microbial metabolites
Broad-spectrum antibiotics can kill harmless bacteria in our intestine, thus facilitating invasion by antibiotic-resistant bacteria such as carbapenem-resistant Enterobacteriaceae (CRE). Here, Yip et al. show that killing gut bacteria with antibiotics leads to enrichment of nutrients and depletion of inhibitory microbial metabolites, which overall potentiates CRE growth.
- Alexander Y. G. Yip
- , Olivia G. King
- & Julie A. K. McDonald
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Article
| Open AccessMenT nucleotidyltransferase toxins extend tRNA acceptor stems and can be inhibited by asymmetrical antitoxin binding
Bacteria can control their growth using internal toxins regulated by antitoxins. Here, the authors show MenT toxins from Mycobacterium tuberculosis work by modifying tRNAs, and asymmetric antitoxin binding blocks toxin activity.
- Xibing Xu
- , Ben Usher
- & Pierre Genevaux
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Article
| Open AccessDeSUMOylation of a Verticillium dahliae enolase facilitates virulence by derepressing the expression of the effector VdSCP8
Verticillium dahliae, a soil-borne fungal pathogen, causes vascular wilt in a wide variety of economically important crops. This study reveals a sophisticated pathogenic mechanism of VdUlpB-deSUMOylated enolase to facilate fungal virulence by derepressing the expression of the effector VdSCP8.
- Xue-Ming Wu
- , Bo-Sen Zhang
- & Hui-Shan Guo
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Article
| Open AccessProfiling cell envelope-antibiotic interactions reveals vulnerabilities to β-lactams in a multidrug-resistant bacterium
The bacterial pathogen Burkholderia cenocepacia and related species are often multidrug resistant because their cell envelope restricts antibiotic penetration. Here, Hogan et al systematically identify genes associated with resistance and susceptibility to cell envelope-targeting antibiotics, providing insights into underlying mechanisms and suggesting avenues for development of improved antibacterial therapies.
- Andrew M. Hogan
- , A. S. M. Zisanur Rahman
- & Silvia T. Cardona
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| 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 AccessSequential roles for red blood cell binding proteins enable phased commitment to invasion for malaria parasites
Malaria parasites invade erythrocytes to proliferate, but visualizing this rapid process is challenging. Here the authors use live imaging and genome-editing of P. knowlesi to dissect invasion and establish the roles of two vital parasite proteins.
- Melissa N. Hart
- , Franziska Mohring
- & Robert W. Moon
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Article
| Open AccessA Phytophthora receptor-like kinase regulates oospore development and can activate pattern-triggered plant immunity
LRR-RLKs are also widespread in plants and oomycete pathogens. Here, the authors report that an LRR-RLK from Phytophthora sojae can activate pattern-triggered immunity in host soybean and nonhost tomato and Nicotiana benthamiana plants.
- Yong Pei
- , Peiyun Ji
- & Daolong Dou
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Article
| Open AccessHerbarium specimen sequencing allows precise dating of Xanthomonas citri pv. citri diversification history
Herbarium collections are an important source of historical DNA, whose analysis can shed light on the evolutionary history of plant pathogens. Here, Campos et al. reconstruct historical genomes of the bacterial crop pathogen Xanthomonas citri pv. citri from citrus herbarium specimens, estimating that the pathogen originated in Southern Asia ~11,500 years ago and diversified during the beginning of the 13th century.
- Paola E. Campos
- , Olivier Pruvost
- & Lionel Gagnevin
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Article
| Open AccessAcquisition, co-option, and duplication of the rtx toxin system and the emergence of virulence in Kingella
The bacterial genus Kingella includes pathogenic species that secrete a toxin called RtxA, which is absent in commensal species. Here, Morreale et al. identify key steps in the evolutionary transition from commensal to pathogen, including horizontal gene transfer of the toxin-encoding genes, co-option of an existing secretion system, and gene duplication.
- Daniel P. Morreale
- , Eric A. Porsch
- & Paul J. Planet
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Article
| Open AccessDecoding a cryptic mechanism of metronidazole resistance among globally disseminated fluoroquinolone-resistant Clostridioides difficile
Detection of resistance to the antibiotic metronidazole in C. difficile often requires the presence of heme in the media, for unclear reasons. Here, the authors show that most metronidazole-resistant strains carry a mutation that promotes expression of a heme-dependent enzyme that degrades nitroimidazoles, and the mutation often co-occurs with an amino-acid substitution in DNA gyrase that confers resistance to another class of antibiotics, fluoroquinolones.
- Abiola O. Olaitan
- , Chetna Dureja
- & Julian G. Hurdle
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Article
| Open AccessA protein kinase coordinates cycles of autophagy and glutaminolysis in invasive hyphae of the fungus Magnaporthe oryzae within rice cells
The blast fungus Magnaporthe oryzae produces invasive hyphae in living rice cells during early infection. Here, the authors show that a fungal protein kinase promotes this biotrophic growth phase by coordinating cycles of autophagy and glutaminolysis in invasive hyphae.
- Gang Li
- , Ziwen Gong
- & Richard A. Wilson
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Article
| Open AccessOn the mechanisms of lysis triggered by perturbations of bacterial cell wall biosynthesis
Inhibition of bacterial cell wall synthesis by β-lactam antibiotics results in a loss of cell wall integrity, but cells die via a combination of downstream events involving metabolic perturbations and oxidative damage. Here, Kawai et al. identify key enzymatic steps that stimulate the generation of reactive oxygen species and highlight the role of iron homeostasis in the lethal effects mediated by oxidative damage.
- Yoshikazu Kawai
- , Maki Kawai
- & Jeff Errington
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Article
| Open AccessInterplay between human STING genotype and bacterial NADase activity regulates inter-individual disease variability
The combination of host and pathogen diversity can result in variability in disease severity between individuals. Here the authors utilise a model of Streptococcus pyogenes infection and show the impact of human STING genotype and bacterial NADase activity on pathology.
- Elin Movert
- , Jaume Salgado Bolarin
- & Fredric Carlsson
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Article
| Open AccessIdentification of the SARS-unique domain of SARS-CoV-2 as an antiviral target
The SARS-unique domain (SUD) of SARS-CoV-2 plays important roles in virus life cycle. Here the authors determine the crystal structure of SARS-CoV-2 SUD and perform a compound screen, which identify theaflavin 3,3’-digallate as a potent SUD binder that exhibits anti-SARS-CoV-2 activity.
- Bo Qin
- , Ziheng Li
- & Sheng Cui
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Article
| Open AccessExtensive diversity in RNA termination and regulation revealed by transcriptome mapping for the Lyme pathogen Borrelia burgdorferi
Transcription termination can tune bacterial gene expression in response to diverse signals. Here, the authors use several RNA-seq approaches to map RNA ends for the transcriptome of the spirochete Borrelia burgdorferi, providing insights into various modes of transcription termination and identifying potential RNA regulators in this pathogen.
- Emily Petroni
- , Caroline Esnault
- & Philip P. Adams
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Article
| Open AccessSingle cell transcriptomics identifies distinct profiles in pediatric acute respiratory distress syndrome
Paediatric acute respiratory distress syndrome (pARDS) is associated with significant mortality and morbidity. Here the authors use single cell sequencing of tracheal aspirate samples from children with pARDS and characterise immune phenotypes and associations with infection stage and pathogen.
- Tim Flerlage
- , Jeremy Chase Crawford
- & Paul G. Thomas
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Article
| Open AccessDprE2 is a molecular target of the anti-tubercular nitroimidazole compounds pretomanid and delamanid
Pretomanid and delamanid are pro-drugs used for the treatment of tuberculosis, but their precise mechanisms of action are unclear. Here, the authors identify an enzyme required for the synthesis of the mycobacterial cell wall as a molecular target of the activated drugs.
- Katherine A. Abrahams
- , Sarah M. Batt
- & Gurdyal S. Besra
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Article
| Open AccessCandida albicans exploits N-acetylglucosamine as a gut signal to establish the balance between commensalism and pathogenesis
The mechanisms by which opportunistic pathogens shift between commensalism and pathogenesis remains poorly understood. Here, the authors show that N-acetylglucosamine, a carbon source enriched in the gut, plays a role in modulating commensal-pathogenic balance in Candida albicans.
- Dandan Yang
- , Mao Zhang
- & Yang Lu
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Article
| Open AccessCampylobacter vaccination reduces diarrheal disease and infant growth stunting among rhesus macaques
Utilising various Campylobacter vaccination regimens, the authors explore the effect of vaccination on Campylobacter-associated diarrhoea, mortality, and growth kinetics in vaccinated infant rhesus macaques.
- Sara M. Hendrickson
- , Archana Thomas
- & Mark K. Slifka
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Article
| Open AccessGenomic epidemiology of Vibrio cholerae during a mass vaccination campaign of displaced communities in Bangladesh
The Cox’s Bazar area of Bangladesh has received a large number of Forcibly Displaced Myanmar Nationals. Cholera outbreaks have been detected in the area, and here, the authors perform genomic surveillance of cholera in the refugee and non-refugee population to infer the risk of epidemic spread.
- Alyce Taylor-Brown
- , Mokibul Hassan Afrad
- & Firdausi Qadri
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Article
| Open AccessMycobacterium abscessus VapC5 toxin potentiates evasion of antibiotic killing by ribosome overproduction and activation of multiple resistance pathways
Mycobacterium abscessus (Mab) infections are difficult to clear with antibiotics. Here the authors show that clinical Mab strains can acquire a toxin-antitoxin system that enhances survival upon treatment with current first-line antibiotics through depletion of tRNASerCGA and subsequent ribosome overproduction.
- Eduardo A. Troian
- , Heather M. Maldonado
- & Nancy A. Woychik