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Clinically used broad-spectrum antibiotics compromise inflammatory monocyte-dependent antibacterial defense in the lung
Authors utilise a murine model of infection to provide mechanistic insight into how antimicrobial therapy may be a predisposing risk factor for hospital-acquired pneumonia. They show that antibiotic-induced microbiota perturbations compromise inflammatory monocytes and thereby impair antibacterial defence.
- Patrick J. Dörner
- , Harithaa Anandakumar
- & Bastian Opitz
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Targeted metagenomics reveals association between severity and pathogen co-detection in infants with respiratory syncytial virus
The impact of other pathogens on disease outcome was studied in European infants with RSV infection. Additional viruses were commonly co-detected during infection but were weakly linked to severity. However, presence of Haemophilus bacteria strongly associated with severe cases.
- Gu-Lung Lin
- , Simon B. Drysdale
- & Andrew J. Pollard
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Tick hemocytes have a pleiotropic role in microbial infection and arthropod fitness
Rolandelli et al. define how immune cells from the tick Ixodes scapularis are affected by infection and show that this cell population have distinct signatures and functions in immunity, metabolism and proliferation.
- Agustin Rolandelli
- , Hanna J. Laukaitis-Yousey
- & Joao H. F. Pedra
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Immune signature of Chlamydia vaccine CTH522/CAF®01 translates from mouse-to-human and induces durable protection in mice
Authors present a comparative immunological characterisation of Chlamydia vaccine, CTH522/CAF®01, in mice and humans. Findings suggest the mouse to be a good predictor of human immunity to the Chlamydia vaccine CTH522/CAF®01, and long-lasting protection in the mouse further supports the development of this promising vaccine candidate.
- Anja W. Olsen
- , Ida Rosenkrands
- & Frank Follmann
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The 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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A convergent evolutionary pathway attenuating cellulose production drives enhanced virulence of some bacteria
Extra-intestinal pathogenic Escherichia coli cause urinary tract and bloodstream infections. Here, the authors show how mutations that disrupt the production of cellulose, a polysaccharide produced by many bacteria, drive enhanced virulence.
- Nguyen Thi Khanh Nhu
- , M. Arifur Rahman
- & Mark A. Schembri
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Gestational diabetes augments group B Streptococcus infection by disrupting maternal immunity and the vaginal microbiota
Here, Marcado-Evans et al show that gestational diabetes enhances group B Streptococcus infection through altering host-microbe dynamics, disrupting maternal immunity, and perturbing the vaginal microbiota in a murine pregnancy model.
- Vicki Mercado-Evans
- , Marlyd E. Mejia
- & Kathryn A. Patras
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A nanoparticle-based sonodynamic therapy reduces Helicobacter pylori infection in mouse without disrupting gut microbiota
Here, the authors develop a non-antibiotic approach using sonodynamic therapy mediated by a lecithin bilayer-coated poly(lactic-co-glycolic) nanoparticle preloaded with verteporfin, Ver-PLGA@Lecithin, to treat Helicobacter pylori.
- Tao Liu
- , Shuang Chai
- & Lihua Yang
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Personalising intravenous to oral antibiotic switch decision making through fair interpretable machine learning
The decision to switch patients from intravenous to oral antibiotic therapy is important for the individual and wider society. Here, authors show a machine learning model using routine clinical data can predict when a patient could switch.
- William J. Bolton
- , Richard Wilson
- & Timothy M. Rawson
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Global emergence of a hypervirulent carbapenem-resistant Escherichia coli ST410 clone
In this work, the authors identified a hypervirulent carbapenem-resistant Escherichia coli ST410 clone which carries a high pathogenicity island and an O-antigen gene cluster. The findings highlight the ongoing evolution of ST410 towards increased resistance and virulence.
- Xiaoliang Ba
- , Yingyi Guo
- & Chao Zhuo
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Genomic and panproteomic analysis of the development of infant immune responses to antigenically-diverse pneumococci
By combining genome sequencing and antibody binding (to all common pneumococcal proteins) data, Croucher et al. present a high-resolution analysis of the emergence of immune responses in children that can protect against pneumonia.
- Nicholas J. Croucher
- , Joseph J. Campo
- & David Goldblatt
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Within-host genetic diversity of extended-spectrum beta-lactamase-producing Enterobacterales in long-term colonized patients
The diversity of ESBL-producing Klebsiella pneumoniae species complex and ESBL-Escherichia coli within patients is low and colonization with the same strain may persist for long periods. Authors utilise clinical and microbiological data from electronic health records to investigate genetic diversity of colonizing and infecting strains.
- Lisandra Aguilar-Bultet
- , Ana B. García-Martín
- & Sarah Tschudin-Sutter
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The genomic epidemiology of shigellosis in South Africa
As a leading cause of diarrhoeal mortality and morbidity, authors examine the epidemiology and genome dynamics of shigellosis in South Africa, utilising whole genome sequence analysis.
- George E. Stenhouse
- , Karen H. Keddy
- & Kate S. Baker
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Enterohaemorrhagic 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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Structural basis for the toxicity of Legionella pneumophila effector SidH
Legionella pneumophila secretes hundreds of effectors to facilitate infection. Here, Sharma et al show that the virulence effector SidH adopts a unique α-helical conformation, leading to toxicity via tRNA binding site and resolve the structural basis of SidH regulation through ubiquitination.
- Rahul Sharma
- , Michael Adams
- & Sagar Bhogaraju
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Self-promoted electroactive biomimetic mineralized scaffolds for bacteria-infected bone regeneration
Infected bone defects are a major challenge in orthopedic treatment. Here, the authors develop an electroactive mineralized scaffold that achieves nearly complete in situ healing of infected bone in rats, rabbits and beagle dogs.
- Zixin Li
- , Danqing He
- & Yan Liu
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Inferring 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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Pasteurella 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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Pathogen-driven degradation of endogenous and therapeutic antibodies during streptococcal infections
Group A streptococcus causes a wide range of human diseases and significantly contributes to morbidity and mortality worldwide. Here, Toledo et al show how streptococcus alters the structure and function of endogenous and therapeutic antibodies during infection and how this is affected by the host microenvironment.
- Alejandro Gomez Toledo
- , Eleni Bratanis
- & Johan Malmström
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A genomic appraisal of invasive Salmonella Typhimurium and associated antibiotic resistance in sub-Saharan Africa
Invasive Salmonella Typhimurium bloodstream infection causes a significant public health burden in sub-Saharan Africa. Here, the authors analyse whole genome sequences of 1,302 S. Typhimurium isolates from Africa and describe its evolution, geographic spread, and antimicrobial resistance characteristics.
- Sandra Van Puyvelde
- , Tessa de Block
- & Octavie Lunguya
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An innate granuloma eradicates an environmental pathogen using Gsdmd and Nos2
Pathogens often persist within granulomas which form to control infection. Here, Harvest et al describe an innate granuloma that eradicates a ubiquitous environmental pathogen without inducing adaptive immunity.
- Carissa K. Harvest
- , Taylor J. Abele
- & Edward A. Miao
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Assessing the global risk of typhoid outbreaks caused by extensively drug resistant Salmonella Typhi
Extensively drug resistant (XDR) typhoid fever is an emerging global health threat. This study compares data on air travel patterns and typhoid incidence to identify countries at high risk for XDR typhoid outbreaks.
- Joseph Walker
- , Chrispin Chaguza
- & Virginia E. Pitzer
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Cryptic susceptibility to penicillin/β-lactamase inhibitor combinations in emerging multidrug-resistant, hospital-adapted Staphylococcus epidermidis lineages
Staphylococcus epidermidis can cause invasive infections that are difficult to treat due to multi-resistance to most clinically relevant drugs, including methicillin and other β-lactam antibiotics, vancomycin, and rifampicin. In this work, the authors use in vitro assays and a mouse infection model to explore cryptic susceptibility and development of resistance to penicillin/β-lactamase combinations.
- Xiaoliang Ba
- , Claire L. Raisen
- & Jesper Larsen
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NAD+ 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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A Glycolipidated-liposomal peptide vaccine confers long-term mucosal protection against Streptococcus pyogenes via IL-17, macrophages and neutrophils
Vaccines that specifically induce immunity against bacterial pathogens are required. Here the authors produce and characterize an intranasal liposomal vaccine against a peptide antigen from Streptococcus pyogenes and show that it induces a strong mucosal IgA response lasting for over one year, and that protection is dependent on cellular immunity mediated through IL-17, macrophages and neutrophils.
- Victoria Ozberk
- , Mehfuz Zaman
- & Manisha Pandey
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Bifidobacteria shape antimicrobial T-helper cell responses during infancy and adulthood
The human immune system changes with age which impacts pathogen clearance. Here, Vogel et al. probe how CD4 + T-cells from different age groups respond to bacteria and show that activation with staphylococcal antigen induces T cells to become Th1-like cells, whilst stimulation with Bifidobacterium infantis induces a regulatory phenotype.
- Katrin Vogel
- , Aditya Arra
- & Monika C. Brunner-Weinzierl
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NLRP3 selectively drives IL-1β secretion by Pseudomonas aeruginosa infected neutrophils and regulates corneal disease severity
Bacterial infection of immune cells can result in engagement of different immunological pathways. Here the authors show that a Pseudomonas aeruginosa type three secretion system exoenzyme is linked to the differential selection of inflammasome usage between macrophages and neutrophils.
- Martin S. Minns
- , Karl Liboro
- & Eric Pearlman
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Exploiting the aggregation propensity of beta-lactamases to design inhibitors that induce enzyme misfolding
Here the authors show that beta-lactamase have an intrinsic aggregation propensity that can be exploited to inactivate these enzymes that mediate antibiotic resistance, using peptides that are based on aggregation prone regions in the sequence of the beta-lactamase.
- Ladan Khodaparast
- , Laleh Khodaparast
- & Joost Schymkowitz
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RUFY3 regulates endolysosomes perinuclear positioning, antigen presentation and migration in activated phagocytes
RUFY proteins are known to regulate autophagy, cytoskeletal dynamics, migration and endosomal trafficking. Here, Char et al. show that iRUFY3 plays a role in perinuclear positioning, phagocyte migration and antigen presentation during Salmonella infection.
- Rémy Char
- , Zhuangzhuang Liu
- & Philippe Pierre
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Roving methyltransferases generate a mosaic epigenetic landscape and influence evolution in Bacteroides fragilis group
Here, Tisza, Dekker, and colleagues perform large scale analysis of genome methylation in the gut commensal and pathogen, Bacteroides fragilis group, revealing immense methyl motif diversity and evidence of widespread methyltransferase exchange among phages.
- Michael J. Tisza
- , Derek D. N. Smith
- & John P. Dekker
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Interplay 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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A pharmacoproteomic landscape of organotypic intervention responses in Gram-negative sepsis
Sepsis can cause organ damage through disparate immunological and metabolic processes. Here the authors demonstrate a proteomics-based scoring strategy for quantifying quantitative and organotypic changes in relationship to dosing, timing, and potential synergistic intervention combinations during sepsis.
- Tirthankar Mohanty
- , Christofer A. Q. Karlsson
- & Johan Malmström
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Monitoring transmission intensity of trachoma with serology
Trachoma is targeted for global elimination as a public health problem by 2030. Here, the authors combine data from 14 African populations to show that IgG in children is a robust approach to monitor transmission as populations approach elimination.
- Christine Tedijanto
- , Anthony W. Solomon
- & Benjamin F. Arnold
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Yersinia pestis genomes reveal plague in Britain 4000 years ago
An extinct prehistoric plague lineage of Yersinia pestis has been documented from Central Europe to Asia during the Late Neolithic and Bronze Age. Here, Swali et al. show that this lineage spread to Europe’s northwestern periphery by sequencing three ~4000 year-old Yersinia pestis genomes from Britain.
- Pooja Swali
- , Rick Schulting
- & Pontus Skoglund
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Prenylcysteine oxidase 1 like protein is required for neutrophil bactericidal activities
Neutrophils play critical roles in the response to infection and their function relies on a range of intrinsic and extrinsic factors. Here the authors show a role for Pcyox1l and link this to metabolic pathways including prenylation and the neutrophil response to infection.
- Anastasiia Petenkova
- , Shelby A. Auger
- & Mihaela Gadjeva
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The impact of introduction of the 10-valent pneumococcal conjugate vaccine on pneumococcal carriage in Nigeria
Nigeria has the highest incidence of pneumococcal disease in Africa and introduced the 10-valent pneumococcal vaccine for infants between 2014 and 2016. Here, the authors conduct repeated cross-sectional surveys to analyse the impact of the vaccination campaign on pneumococcal carriage and serotype distribution.
- Aishatu L. Adamu
- , J. Ojal
- & Ifedayo M. O. Adetifa
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A 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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Structural basis for botulinum neurotoxin E recognition of synaptic vesicle protein 2
Botulinum neurotoxin E (BoNT/E) is a major cause of botulism and paradoxically also a drug in clinical trial. Here, the authors show that BoNT/E binding and uptake require glycosylation of its host receptor SV2 with high selectivity for SV2A and SV2B over SV2C.
- Zheng Liu
- , Pyung-Gang Lee
- & Rongsheng Jin
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Transcription tuned by S-nitrosylation underlies a mechanism for Staphylococcus aureus to circumvent vancomycin killing
Antibiotic resistance in Staphylococcus aureus is increasingly emerging. Here, Shu et al demonstrate that transcriptional regulation by S-nitrosylation underlies vancomycin resistance.
- Xueqin Shu
- , Yingying Shi
- & Baolin Sun
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Human CEACAM1 is targeted by a Streptococcus pyogenes adhesin implicated in puerperal sepsis pathogenesis
Infection with Streptococcus pyogenes after childbirth can have life threatening consequences. Here, Catton et al. show that the epidemiologically associated bacterial R28 protein targets the human CEACAM1 receptor to facilitate the pathogenesis of bacterial sepsis.
- Erin A. Catton
- , Daniel A. Bonsor
- & Alex J. McCarthy
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Legionella para-effectors target chromatin and promote bacterial replication
Legionella pneumophilia is known to secrete more than 300 effectors via a type IV secretion system. Here, Schator et al. characterise how the chromatin modifying effectors RomA and LphD work synergistically to hijack host responses and facilitate bacterial replication.
- Daniel Schator
- , Sonia Mondino
- & Monica Rolando
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Repurposing host-guest chemistry to sequester virulence and eradicate biofilms in multidrug resistant Pseudomonas aeruginosa and Acinetobacter baumannii
Rapid antibiotic resistance in bacteria is putting pressure on both existing therapies as well as the development pipeline. Here, the authors present a dual-acting anti-virulence treatment that evades antibiotic resistance mechanisms and remains effective against Top Priority pathogens.
- Christopher Jonkergouw
- , Ngong Kodiah Beyeh
- & Markus B. Linder
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The 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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The genomic epidemiology of Escherichia albertii infecting humans and birds in Great Britain
Escherichia albertii is an emerging gastrointestinal pathogen that causes disease in humans and animals, notably birds. In this genomic epidemiology study, the authors investigate characteristics of isolates sampled from humans and birds in Great Britain and find that they tend to cluster separately.
- Rebecca J. Bengtsson
- , Kate S. Baker
- & Becki Lawson
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Modulation of MRSA virulence gene expression by the wall teichoic acid enzyme TarO
The two-component regulatory system VraRS regulates transcription of penicillin-binding protein 2 in response to cell wall antimicrobials. Here, Lu et al. show that an enzyme from the wall teichoic acid biosynthetic pathway of MRSA can also modulate the expression of virulence factors such as Staphylococcal protein A via VraRS.
- Yunfu Lu
- , Feifei Chen
- & Lefu Lan
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Integrative omics identifies conserved and pathogen-specific responses of sepsis-causing bacteria
Severe sepsis has a high mortality rate. Here, the authors provide genomic, transcriptomic, proteomic and metabolomic data across four sepsis-causing pathogens and identify a signature of global increase in fatty acid and lipid biosynthesis as well as cholesterol acquisition.
- Andre Mu
- , William P. Klare
- & Mark J. Walker
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A mycobacterial effector promotes ferroptosis-dependent pathogenicity and dissemination
Ferroptosis is an iron-dependent form of cell death whose role in infectious diseases is being elucidated. Here, Qiang et al. show that PtpA, an effector secreted by Mycobacterium tuberculosis, induces ferroptosis by hijacking host arginine methyltransferase PRMT6 to promote its pathogenicity and dissemination.
- Lihua Qiang
- , Yong Zhang
- & Jing Wang
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Single molecule analyses reveal dynamics of Salmonella translocated effector proteins in host cell endomembranes
Salmonella typhimurium translocates numerous effectors via its type III secretion system. Here, Göser et al. present a characterisation of selected proteins and their dynamic interaction with Salmonella-containing vacuoles and – induced filaments.
- Vera Göser
- , Nathalie Sander
- & Michael Hensel
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N6-methyladenosine of Spi2a attenuates inflammation and sepsis-associated myocardial dysfunction in mice
N6-methyladenosine (m6A) methylation of RNA is a common type of RNA modification that regulates gene expression. Here, the authors report m6A methylation of serpin 2 A negatively regulates inflammation and reduces heart dysfunction in the setting of sepsis.
- Xiangyu Wang
- , Yan Ding
- & Jie Du
Overlapping Streptococcus pyogenes and Streptococcus dysgalactiae subspecies equisimilis household transmission and mobile genetic element exchange