Featured
-
-
Article
| Open Access
Cryo-EM structures of Candida albicans Cdr1 reveal azole-substrate recognition and inhibitor blocking mechanisms
Candida albicans Cdr1 pumps azole antifungal drugs out of the cell, driving drug resistance. Here, the authors determine the mechanism of Cdr1-mediated fluconazole resistance and milbemycin oxime inhibition, providing a foundation for future drug discovery efforts.
- Ying Peng
- , Yan Lu
- & Zhaofeng Yan
-
Article
| Open Access
Towards clinically relevant dose ratios for Cabamiquine and Pyronaridine combination using P. falciparum field isolate data
Here the authors use drug susceptibility data from Plasmodium falciparum field isolates in a pharmacometric model to evaluate cabamiquine and pyronaridine efficacy, both individually and in combination. The combined treatment shows over 90% parasite reduction in most simulated cases, providing valuable guidance for clinical dose selection in real-world settings.
- Mohamed Maiga
- , Laurent Dembele
- & Claudia Demarta-Gatsi
-
Article
| Open Access
A Foundation Model Identifies Broad-Spectrum Antimicrobial Peptides against Drug-Resistant Bacterial Infection
New approaches to develop antimicrobial agents are urgently needed. In this study, the authors develop a peptide language-based deep generative model to design broad-spectrum antimicrobial peptides against drug-resistant bacteria and validate promising candidates in a wound mouse model.
- Tingting Li
- , Xuanbai Ren
- & Feixiong Cheng
-
Article
| Open Access
Giant viruses as reservoirs of antibiotic resistance genes
Nucleocytoplasmic large DNA viruses, or ‘giant viruses’, infect a wide range of eukaryotes and can exchange genetic material not only with their hosts but also with bacteria and phages. Here, the authors show that many giant viruses carry diverse antibiotic resistance genes, which are associated with mobile genetic elements and genes encoding potential virulence factors.
- Xinzhu Yi
- , Jie-Liang Liang
- & Jin-tian Li
-
Article
| Open Access
Nanopore R10.4 metagenomic detection of blaCTX-M/blaDHA antimicrobial resistance genes and their genetic environments in stool
In this work, authors employ Nanopore-based shotgun metagenomic sequencing for the screening of antimicrobial resistance genes (blaCTX-M/blaDHA) in human stool samples.
- Edgar I. Campos-Madueno
- , Claudia Aldeia
- & Andrea Endimiani
-
Article
| Open Access
Synergistic collaboration between AMPs and non-direct antimicrobial cationic peptides
Antimicrobial peptides and non-direct antimicrobial cationic peptides are secreted in response to invasive pathogens. Here, Ye et al show that there is a synergistic interaction between these two types of expressed peptides from the amphibian frog Amolops wuyiensis.
- Zifan Ye
- , Lei Fu
- & Yipeng Wang
-
Article
| Open Access
Multiplex real-time PCR in non-invasive respiratory samples to reduce antibiotic use in community-acquired pneumonia: a randomised trial
Here, the authors report the results of a randomised trial assessing whether adding multiplex real-time PCR to conventional testing reduces antibiotic use in community-acquired pneumonia and observe no significant reduction in days of antibiotic therapy or in 30-day mortality.
- Gabriela Abelenda-Alonso
- , Laura Calatayud
- & Jordi Carratalà
-
Article
| Open Access
Clonal background and routes of plasmid transmission underlie antimicrobial resistance features of bloodstream Klebsiella pneumoniae
Authors perform a genomic analyses of 136 Klebsiella pneumoniae isolates, revealing that both the genetic background of host strains and the routes of plasmid transmission influence the spread of antimicrobial resistance in bloodstream infections.
- Odion O. Ikhimiukor
- , Nicole I. Zac Soligno
- & Cheryl P. Andam
-
Article
| Open Access
Community use of oral antibiotics transiently reprofiles the intestinal microbiome in young Bangladeshi children
In this study, the authors examined the relationship between oral antibiotic use and composition and antimicrobial resistance in the gut microbiome in Bangladeshi infants with a high exposure to community-administered antibiotics.
- Andrew Baldi
- , Sabine Braat
- & Sant-Rayn Pasricha
-
Article
| Open Access
Dynamic PET reveals compartmentalized brain and lung tissue antibiotic exposures of tuberculosis drugs
Antibiotic treatments for tuberculous meningitis, the deadliest form of tuberculosis, are not optimized. Here, PET in human and animal studies is used to measure the biodistribution of several antibiotics to develop optimized regimens for drug-resistant tuberculous meningitis.
- Xueyi Chen
- , Bhavatharini Arun
- & Sanjay K. Jain
-
Article
| Open Access
An unusual two-strain cholera outbreak in Lebanon, 2022-2023: a genomic epidemiology study
Here the authors provide results from a genomic epidemiology study of a cholera outbreak in Lebanon, showing that it was caused by two Vibrio cholerae strains of serogroup O1 (El Tor biotype), namely an AFR15 sublineage related to South Asian isolates and extensively drug-resistant Yemeni AFR13.
- Antoine Abou Fayad
- , Rayane Rafei
- & Ghassan M. Matar
-
Article
| Open Access
Membrane depolarization kills dormant Bacillus subtilis cells by generating a lethal dose of ROS
The bactericidal activity of several antibiotics partially relies on production of reactive oxygen species (ROS), which requires the Fenton reaction. Here, the authors show that membrane depolarization also leads to ROS production, but this occurs via other mechanisms that do not require the Fenton reaction.
- Declan A. Gray
- , Biwen Wang
- & Leendert W. Hamoen
-
Article
| Open Access
A synthetic peptide mimic kills Candida albicans and synergistically prevents infection
Fungal infections are severely underestimated as a cause of mortality, and alternative drugs are urgently needed. Here, Schaefer et al. show that a synthetic polymer mimicking defensins shows different, but synergistic activity with known antifungals.
- Sebastian Schaefer
- , Raghav Vij
- & Sascha Brunke
-
Article
| Open Access
Restriction of arginine induces antibiotic tolerance in Staphylococcus aureus
Utilising proteomic and transposon sequencing screens, Freiberg et al. identified arginine metabolism enzymes that impact tolerance to antibiotics in Staphylococcus aureus, including in animal models of skin and bone infections.
- Jeffrey A. Freiberg
- , Valeria M. Reyes Ruiz
- & Eric P. Skaar
-
Article
| Open Access
RNA polymerase stalling-derived genome instability underlies ribosomal antibiotic efficacy and resistance evolution
Bacteria evolve antibiotic resistance via genetic mutations, but the process remains somewhat unclear. This work finds that the disruption of transcription-translation coupling is crucial for mutagenesis caused by ribosome-targeting antibiotics in Escherichia coli.
- Yayun Zheng
- , Ruochen Chai
- & Jintao Liu
-
Article
| Open Access
Adaptative survival of Aspergillus fumigatus to echinocandins arises from cell wall remodeling beyond β−1,3-glucan synthesis inhibition
Echinocandins inhibit the biosynthesis of β−1,3-glucan, an essential component of the fungal cell wall, but their efficacy against the pathogen Aspergillus fumigatus is limited. Here, Dickwella Widanage et al. show that A. fumigatus responds to echinocandin treatment by remodelling various cell wall polymers, thus maintaining cell wall integrity and modulating the permeability and circulation of the drug in the cell wall.
- Malitha C. Dickwella Widanage
- , Isha Gautam
- & Tuo Wang
-
Article
| Open Access
Botrytis cinerea combines four molecular strategies to tolerate membrane-permeating plant compounds and to increase virulence
Plant saponins are secondary metabolites with broad antimicrobial toxicity. Here, You et al. characterize the mechanisms by which the fungus Botrytis cinerea establishes tolerance to saponins.
- Yaohua You
- , H. M. Suraj
- & Jan A. L. van Kan
-
Article
| Open Access
A bacteriocin expression platform for targeting pathogenic bacterial species
Bacteriocins are antimicrobial peptides that are naturally produced by many bacteria. In this work, authors develop a bacteriocin secretion platform, and test, in a proof-of-concept study, antimicrobial efficacy against Enterococcus faecalis and Enterococcus faecium.
- Jack W. Rutter
- , Linda Dekker
- & Chris P. Barnes
-
Article
| Open Access
Toxic eburicol accumulation drives the antifungal activity of azoles against Aspergillus fumigatus
Azole antifungals inhibit the ergosterol biosynthesis enzyme CYP51, but their effects on fungal viability and growth vary greatly among fungal species. Here, the authors provide evidence that the mode of action of azoles against Aspergillus fumigatus relies on accumulation of the CYP51 substrate eburicol, which exerts fungicidal effects by triggering cell-wall carbohydrate patch formation.
- Hesham Elsaman
- , Evgeny Golubtsov
- & Johannes Wagener
-
Editorial
| Open AccessAntimicrobial resistance: a silent pandemic
Antimicrobial resistance (AMR) occurs when microorganisms (bacteria, viruses, fungi and parasites) no longer respond to antimicrobials, rendering these specific treatments ineffective. Subsequently, this narrows the options for clinical treatment and increases the risk of complications, hospital admissions, and mortality rates. Ultimately, infections become more difficult to treat. The concern of AMR is not new, yet the COVID-19 pandemic has further highlighted this global burden and raised questions regarding the preparedness for the fight against increasing cases of AMR. In a joint collaboration, Nature Communications, Nature Microbiology, Nature Medicine, Communications Medicine and Scientific Reports have launched a Collection and call for papers, inviting submissions of papers that advance our understanding of all aspects of AMR, as outlined in the Collection scope.
-
Article
| Open Access
A synthetic antibiotic class with a deeply-optimized design for overcoming bacterial resistance
Authors present the in vivo assessment of a compound, F8, from a synthetic antibiotic class, showing efficacy against antibiotic resistance bacteria and insight into its mechanism of action.
- Jin Feng
- , Youle Zheng
- & Xu Wang
-
Article
| Open Access
Prolonged hospitalization signature and early antibiotic effects on the nasopharyngeal resistome in preterm infants
Here, the authors use metagenomics to study the resistome development in the nasopharynx of preterm infants during early life, uncovering a dynamic environment affected by early-life antibiotics and showing long-lasting signature of hospitalization.
- Achal Dhariwal
- , Polona Rajar
- & Fernanda Cristina Petersen
-
Article
| Open Access
Pneumococcal competence is a populational health sensor driving multilevel heterogeneity in response to antibiotics
Stress exposure shapes survival mechanisms in bacteria. Here, the authors show that individual pneumococcal cells react to stress by competence self-induction, which may propagate to non-competent cells, promoting multilevel heterogeneity and favouring survival.
- Marc Prudhomme
- , Calum H. G. Johnston
- & Patrice Polard
-
Article
| Open Access
Population structure and antibiotic resistance of swine extraintestinal pathogenic Escherichia coli from China
Extraintestinal pathogenic E. coli (ExPEC) is a significant cause of human and animal disease. Here, the authors compile a collection of 499 ExPEC samples from swine in China and characterise their phylogenetic population structure and antibiotic resistance profiles.
- Xudong Li
- , Huifeng Hu
- & Chen Tan
-
Article
| Open Access
Tyrosol blocks E. coli anaerobic biofilm formation via YbfA and FNR to increase antibiotic susceptibility
Biofilm cells display remarkable resistance to antibiotics. Here, the authors report that tyrosol blocks Escherichia coli anaerobic biofilm formation by enhancing NO production via YbfA and FNR, thereby increasing biofilm cell susceptibility to antibiotics.
- Ha-Young Choi
- & Won-Gon Kim
-
Article
| Open Access
Stable peptide-assembled nanozyme mimicking dual antifungal actions
Natural antimicrobial peptides and enzymes are good candidates for application but suffer from low stability. Here, the authors report on biomimetic self-assembling peptides which mimic both antimicrobial peptide and enzyme functionality, demonstrating application against fungal infection.
- Ye Yuan
- , Lei Chen
- & Lizeng Gao
-
Article
| Open Access
Structural basis for differential inhibition of eukaryotic ribosomes by tigecycline
Tigecycline is widely used to treat complex bacterial infections. Here, authors present cryo-EM structures of tigecycline-bound eukaryotic ribosomes, revealing how it also targets the human mitoribosome with distinct binding properties.
- Xiang Li
- , Mengjiao Wang
- & Jingdong Cheng
-
Article
| Open Access
Detection of hidden antibiotic resistance through real-time genomics
This study on a multi-drug resistant infection case shows that real-time genomics can detect low-abundance plasmid-encoded resistance missed by established diagnostics.
- Ela Sauerborn
- , Nancy Carolina Corredor
- & Lara Urban
-
Article
| Open Access
VirBR, a transcription regulator, promotes IncX3 plasmid transmission, and persistence of blaNDM-5 in zoonotic bacteria
Carbapenem-resistant Escherichia coli, carrying blaNDM-5-IncX3 plasmids, can persist in chickens either under the presence of amoxicillin or without any antibiotic. Transcriptional regulator VirBR can promote transmission of IncX3 plasmid and persistence of blaNDM-5 in zoonotic bacteria.
- Tengfei Ma
- , Ning Xie
- & Jianzhong Shen
-
Article
| Open Access
Beta-lactamase dependent and independent evolutionary paths to high-level ampicillin resistance
Bacterial resistance to beta-lactam antibiotics is on the rise, but laboratory evolution studies do not always recapitulate clinical resistance levels. Here, the authors select Escherichia coli mutants with varying degrees of beta-lactam resistance, showing that combinations of distinct genetic mutations, accessible at large population sizes, can drive high-level resistance independently of beta-lactamases.
- Rotem Gross
- , Idan Yelin
- & Roy Kishony
-
Article
| Open Access
Guiding antibiotics towards their target using bacteriophage proteins
Zhao et al. demonstrate a strategy that delivers antibiotics to the site of infection using proteins from bacteriophages, which naturally target bacteria. This approach helps the antibiotic regain activity against conventionally resistant strains.
- Xinghong Zhao
- , Xinyi Zhong
- & Hongping Wan
-
Article
| Open Access
Broad-spectrum activity against mosquito-borne flaviviruses achieved by a targeted protein degradation mechanism
Developing broad antiviral drugs against dengue is challenging due to genetic diversity. Here, the authors generate PROTACs targeting the dengue virus envelope protein demonstrating improved potency and broadened activity against other mosquito-borne flaviviruses as compared to the parental inhibitors.
- Han-Yuan Liu
- , Zhengnian Li
- & Priscilla L. Yang
-
Article
| Open Access
Deep sequencing of Escherichia coli exposes colonisation diversity and impact of antibiotics in Punjab, Pakistan
E coli is an important cause of infection globally but there is limited understanding of the genetic diversity of strains circulating in South Asia. Here, the authors characterise strains in Punjab province, Pakistan by assembling >5,000 genomes sampled from outpatients and community dwellers.
- Tamim Khawaja
- , Tommi Mäklin
- & Anu Kantele
-
Article
| Open Access
Aryl amino acetamides prevent Plasmodium falciparum ring development via targeting the lipid-transfer protein PfSTART1
Compound MMV006833 inhibits ring-stage development of Plasmodium falciparum. Here, the authors show that it targets lipid transfer enzyme PfSTART1 and prevents PfSTART1 from expanding the vacuole membrane encasing the parasite after red blood cell invasion, thereby blocking parasite growth.
- Madeline G. Dans
- , Coralie Boulet
- & Paul R. Gilson
-
Article
| Open Access
Organic fertilization co-selects genetically linked antibiotic and metal(loid) resistance genes in global soil microbiome
In this study, the authors analyzed global metagenomic data from agricultural soils and show that organic fertilization co-selects for antibiotic and metal(loid) resistance genes in genomic elements, while metatranscriptomic data additionally provides evidence for co-regulation of these gene sets.
- Zi-Teng Liu
- , Rui-Ao Ma
- & Si-Yu Zhang
-
Article
| Open Access
A bispecific antibody exhibits broad neutralization against SARS-CoV-2 Omicron variants XBB.1.16, BQ.1.1 and sarbecoviruses
In this study, the authors develop a potent bispecific antibody targeting two epitopes within the SARS-CoV-2 receptor binding domain and showing robust prophylactic and therapeutic efficacy against XBB.1 infection in mice.
- Yingdan Wang
- , Aihua Hao
- & Lei Sun
-
Article
| Open Access
Functional analysis of the Aspergillus fumigatus kinome identifies a druggable DYRK kinase that regulates septal plugging
Azole antifungals are used to treat lung diseases caused by the pathogenic fungus Aspergillus fumigatus, but resistance is rising. Here, the authors generate a library of >100 protein kinase mutants of A. fumigatus, and show that loss of function or pharmacological inhibition of kinase YakA results in hypersensitivity to azoles and reduced pathogenicity.
- Norman van Rhijn
- , Can Zhao
- & Michael J. Bromley
-
Article
| Open Access
Rule-based omics mining reveals antimicrobial macrocyclic peptides against drug-resistant clinical isolates
This study reports the genomics- and metabolomics-guided discovery of aminovinyl-(methyl-)cysteine-containing peptides (ACyP). One of these peptides, massatide A, demonstrates excellent activity against drug-resistant gram-positive pathogens.
- Zhuo Cheng
- , Bei-Bei He
- & Yong-Xin Li
-
Article
| Open Access
An effective and rapidly degradable disinfectant from disinfection byproducts
Here, authors highlight ecological risks of a widely used disinfectant, chloroxylenol, and identify a more efficient and safer alternative from halo-phenolic disinfection byproducts, 2,6-dichlorobenzoquinone. They leverage seawater’s slightly alkaline nature to enhance its degradability via hydrolysis.
- Jiarui Han
- , Wanxin Li
- & Xiangru Zhang
-
Article
| Open Access
β-lactamase expression induces collateral sensitivity in Escherichia coli
In this work, authors show that β-lactamase enzymes not only confer antibiotic resistance but also increase susceptibility to other antibiotics.
- Cristina Herencias
- , Laura Álvaro-Llorente
- & Jerónimo Rodríguez-Beltrán
-
Article
| Open Access
Potent activity of polymyxin B is associated with long-lived super-stoichiometric accumulation mediated by weak-affinity binding to lipid A
Polymyxins are last-resort antibiotics targeting lipid A in the gram-negative outer membrane. Here, the authors use surface plasmon resonance-based kinetics to reveal a three-state mechanism governing superstoichiometric accumulation of polymyxins.
- Kerry R. Buchholz
- , Mike Reichelt
- & John G. Quinn
-
Article
| Open Access
The sterol C-24 methyltransferase encoding gene, erg6, is essential for viability of Aspergillus species
Antifungal triazoles inhibit biosynthesis of ergosterol, a crucial component of the fungal plasma membrane. Here, Xie et al. show that Erg6, the enzyme that catalyzes a previous step in ergosterol biosynthesis, is essential for the viability of Aspergillus fumigatus, and its repression reduces the virulence of this fungal pathogen in an animal model of infection.
- Jinhong Xie
- , Jeffrey M. Rybak
- & Jarrod R. Fortwendel
-
Article
| Open Access
Genomic insights unveil the plasmid transfer mechanism and epidemiology of hypervirulent Klebsiella pneumoniae in Vietnam
Hypervirulent Klebsiella pneumoniae (hvKp) is a significant cause of severe community-acquired infection, primarily in Asia. Here, the authors characterise the genetic profile, phylogenetic structure, and plasmid features of hvKp in Vietnam.
- Quynh Nguyen
- , Nguyen Yen Thi Phuong
- & Duy Thanh Pham
-
Article
| Open Access
Dynamic microfluidic single-cell screening identifies pheno-tuning compounds to potentiate tuberculosis therapy
Tuberculosis is a major global health threat. Here, the authors develop a single-cell drug discovery approach and identify a compound that tunes bacterial phenotypic variation. This enhances the activity of anti-tubercular drugs against the pathogen.
- Maxime Mistretta
- , Mena Cimino
- & Giulia Manina
-
Article
| Open Access
Targeted protein degradation in mycobacteria uncovers antibacterial effects and potentiates antibiotic efficacy
Efforts to apply targeted protein degradation for antibiotic development are limited by our understanding of prokaryotic protein degradation. Here, the authors establish a chemical-genetic platform and predictive model to determine the degradation potential of essential mycobacterial proteins.
- Harim I. Won
- , Samuel Zinga
- & Junhao Zhu
-
Article
| Open Access
Targeting bacterial nickel transport with aspergillomarasmine A suppresses virulence-associated Ni-dependent enzymes
Aspergillomarasmine A (AMA) chelates metal ions such as Zn2+ and Ni2+, which are essential for the activity of enzymes that are important for virulence of several pathogens. Here, Sychantha et al. show that AMA inhibits bacterial Ni2+ uptake and Ni-dependent enzymes, and reduces bacterial virulence in an animal infection model.
- David Sychantha
- , Xuefei Chen
- & Gerard D. Wright
-
Article
| Open Access
Multimodal binding and inhibition of bacterial ribosomes by the antimicrobial peptides Api137 and Api88
Proline-rich antimicrobial peptides (PrAMPs) inhibit bacterial protein biosynthesis. Here, the authors show that the honey-bee derived PrAMPs Api137 and Api88 inhibit bacterial ribosomes through multiple mechanisms, promising for drug development.
- Simon M. Lauer
- , Maren Reepmeyer
- & Ralf Hoffmann
-
Article
| Open Access
Three concurrent mechanisms generate gene copy number variation and transient antibiotic heteroresistance
Bacterial heteroresistance is a medically relevant phenotype where small antibiotic-resistant subpopulations coexist within predominantly susceptible bacterial populations. Here, Nicoloff et al. describe how three different mechanisms that increase the copy number of resistance genes can lead to unstable and transient heteroresistance.
- Hervé Nicoloff
- , Karin Hjort
- & Helen Wang
-
Article
| Open Access
An oxylipin signal confers protection against antifungal echinocandins in pathogenic aspergilli
Echinocandins are antifungal drugs that inhibit hyphal growth and induce lysis of hyphal tip compartments in pathogenic Aspergillus species. Here, Calise et al. show that echinocandins induce production of a fungal oxylipin signal, thus triggering hyphal growth changes that reduce hyphal tip lysis and confer echinocandin tolerance.
- Dante G. Calise
- , Sung Chul Park
- & Nancy P. Keller
Population genomics of Streptococcus mitis in UK and Ireland bloodstream infection and infective endocarditis cases