Featured
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Editorial |
A new class of antibiotics is cause for cautious celebration — but the economics must be fixed
The threat of antimicrobial resistance means that new antibiotics need to be used sparingly. Governments must support their development with a long-term funding plan.
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News & Views |
A new type of antibiotic targets a drug-resistant bacterium
Infections caused by drug-resistant strains of the bacterium Acinetobacter baumannii have been hard to treat in the clinic. A new class of antibiotics has been identified with the potential to tackle these microbes.
- Morgan K. Gugger
- & Paul J. Hergenrother
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Article
| Open Access
A new antibiotic traps lipopolysaccharide in its intermembrane transporter
A mechanism of lipid transport inhibition has been identified for a class of peptide antibiotics effective against resistant Acinetobacter strains, which may have applications in the inhibition of other Gram-negative pathogens.
- Karanbir S. Pahil
- , Morgan S. A. Gilman
- & Daniel Kahne
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Article
| Open Access
A novel antibiotic class targeting the lipopolysaccharide transporter
A tethered macrocyclic peptide antibiotic class described here—which shows potent antibacterial activity against carbapenem-resistant Acinetobacter baumannii—blocks the transport of bacterial lipopolysaccharide from the inner membrane to its destination on the outer membrane through inhibition of the LptB2FGC complex.
- Claudia Zampaloni
- , Patrizio Mattei
- & Kenneth A. Bradley
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Research Briefing |
‘Explainable’ AI identifies a new class of antibiotics
An artificial-intelligence graph neural network was trained on experimental data and used to identify chemical substructures that underlie selective antibiotic activity in more than 12 million compounds. This led to the discovery of a class of antibiotics with in vitro and in vivo activity against Gram-positive bacteria, including Staphylococcus aureus.
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Article |
Discovery of a structural class of antibiotics with explainable deep learning
An explainable deep learning model using a chemical substructure-based approach for the exploration of chemical compound libraries identified structural classes of compounds with antibiotic activity and low toxicity.
- Felix Wong
- , Erica J. Zheng
- & James J. Collins
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Spotlight |
The fight against antimicrobial resistance
India is developing local solutions to a global problem that was exacerbated by the COVID-19 pandemic.
- Bianca Nogrady
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News Explainer |
What’s behind China’s mysterious wave of childhood pneumonia?
Scientists expected a surge in respiratory disease, but what is happening in China is unusual.
- Gemma Conroy
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Article |
Porin-independent accumulation in Pseudomonas enables antibiotic discovery
We use a whole-cell accumulation assay to assess the ability of non-antibiotic, structurally diverse small molecules to accumulate in Pseudomonas aeruginosa, with potential application in developing drugs to target this pathogen.
- Emily J. Geddes
- , Morgan K. Gugger
- & Paul J. Hergenrother
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News |
‘Groundbreaking’: first treatment targeting ‘super-gonorrhoea’ passes trial
Antibiotic could turn the tide on drug-resistant form of the infection — if it’s used wisely.
- Ewen Callaway
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Article
| Open Access
A molnupiravir-associated mutational signature in global SARS-CoV-2 genomes
A specific class of long phylogenetic branches, distinguished by a high proportion of G-to-A and C-to-T mutations, are almost exclusively found in sequences from 2022, after molnupiravir treatment was introduced, indicating that molnupiravir treatment can give rise to viable mutagenized viruses.
- Theo Sanderson
- , Ryan Hisner
- & Christopher Ruis
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Article
| Open Access
High-resolution landscape of an antibiotic binding site
A collection of RNA polymerase mutants spanning all possible substitutions of the rifampicin binding site is generated and characterized, increasing our understanding of antibiotic mechanisms and bacterial physiology.
- Kevin B. Yang
- , Maria Cameranesi
- & Evgeny Nudler
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Research Briefing |
Step-by-step assembly of a β-barrel protein in a bacterial membrane
Gram-negative bacteria that are resistant to multiple drugs cannot survive without the cell-surface machinery that builds a β-barrel pore structure from outer membrane proteins. Snapshots of different stages in the assembly process provide insights into this crucial mechanism, and could lead to the development of new antibiotics.
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News |
One MRI for 4.7 million people: the battle to treat Syria’s earthquake survivors
With only 64 X-ray and 73 kidney-dialysis machines, 7 CT scanners and one MRI machine, doctors in northwest Syria are racing against the clock to treat 8,500 injuries.
- Miryam Naddaf
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News |
An abundance of antibiotics, and more — this week’s best science graphics
Three charts from the world of research, selected by Nature editors.
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News |
Antibiotic use in farming set to soar despite drug-resistance fears
Analysis finds antimicrobial drug use in agriculture is much higher than reported.
- Sara Reardon
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News |
How antidepressants help bacteria resist antibiotics
A laboratory study unravels ways non-antibiotic drugs can contribute to drug resistance.
- Liam Drew
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Research Briefing |
Bacterial receptor crucial for antibiotic resistance imaged in detail
The bacterial protein BlaR1 regulates resistance to β-lactam antibiotics in the multidrug-resistant bacteria, Staphylococcus aureus. Cryo-electron microscopy has revealed the detailed structures of BlaR1 in its resting state and in its β-lactam-bound activated state, illuminating possible routes to combating antibiotic resistance.
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Article
| Open Access
Structural basis of broad-spectrum β-lactam resistance in Staphylococcus aureus
Cryo-electron microscopy structures of Staphylococcus aureus BlaR1 reveal dynamic signalling states regulating broad spectrum β-lactam antibiotic resistance through cleavage of the transcriptional repressor BlaI and induced expression of the β-lactamase blaZ and the β-lactam-resistant cell-wall transpeptidase mecA.
- J. Andrew N. Alexander
- , Liam J. Worrall
- & Natalie C. J. Strynadka
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Nature Index |
Three ways to combat antimicrobial resistance
With a dearth of new antibiotics coming to market, researchers are finding creative ways to keep bacteria at bay.
- Benjamin Plackett
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Nature Index |
Tackle antimicrobial resistance with a pandemic-style mobilization
Solving the public health crisis will take time, money and cooperation.
- David Hyun
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News |
Push to use antibiotics to prevent sexually transmitted infections raises concerns
The strategy has been shown to reduce STIs, but could increase antimicrobial resistance.
- Dyani Lewis
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Article
| Open Access
Multiple pathways for SARS-CoV-2 resistance to nirmatrelvir
Nirmatrelvir, an oral antiviral targeting the 3CL protease of SARS-CoV-2, has been demonstrated to be clinically useful against COVID-19, but viral resistance to the drug was found to arise readily via multiple pathways in vitro.
- Sho Iketani
- , Hiroshi Mohri
- & David D. Ho
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Article |
Antibiotic combinations reduce Staphylococcus aureus clearance
Different pairs of antibiotics show qualitatively different bacterial clearance interactions—some pairs show reciprocal suppression whereby the drug mixture efficacy is weaker than the individual drugs alone, and the clearance efficacy decreases as more drugs are added.
- Viktória Lázár
- , Olga Snitser
- & Roy Kishony
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Article
| Open Access
Teixobactin kills bacteria by a two-pronged attack on the cell envelope
Using a combination of methods, the mechanism of the antibiotic teixobactin is revealed.
- Rhythm Shukla
- , Francesca Lavore
- & Markus Weingarth
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News & Views |
Bacterial envelope built to a peptidoglycan tune
How a bacterium coordinates the assembly of its outer layers, and couples the formation of this envelope to cell growth and division, is not fully understood. Assessing the role of peptidoglycan molecules provides some answers.
- Michaël Deghelt
- & Jean-François Collet
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Article |
Characterization and antiviral susceptibility of SARS-CoV-2 Omicron BA.2
Isolates of authentic SARS-CoV-2 variants BA.1 and BA.2 exhibit similar infectivity and pathogenicity and show susceptibility to neutralizing therapeutic antibodies and antiviral compounds in mouse and hamster models.
- Ryuta Uraki
- , Maki Kiso
- & Yoshihiro Kawaoka
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Technology Feature |
Methods combine to decode the biology of tuberculosis
Scientists are fusing sequencing, chemistry and imaging techniques to probe interactions between pathogens and their host cells.
- Amber Dance
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Research Briefing |
How the antibiotic fidaxomicin targets an intestinal pathogen
The antibiotic fidaxomicin acts selectively on the bacterium Clostridioides difficile, a main cause of intestinal infections. Structural and biochemical experiments reveal a region in the enzyme RNA polymerase that can sensitize the pathogen to fidaxomicin, helping to explain the drug’s selective clinical activity.
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Article |
Basis of narrow-spectrum activity of fidaxomicin on Clostridioides difficile
Structural analysis of Clostridioides difficile RNA polymerase in complex with fidaxomicin combined with biochemical, genetic and bioinformatic analyses identifies a key residue that determines fidaxomicin sensitivity.
- Xinyun Cao
- , Hande Boyaci
- & Elizabeth A. Campbell
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Where I Work |
Investigating the micropumps behind antibiotic resistance
Juan-Carlos Jiménez Castellanos is helped in his work by an assay-stacking robot.
- Nic Fleming
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Article
| Open Access
Antibody evasion properties of SARS-CoV-2 Omicron sublineages
A study reports on the antigenic characterization of SARS-CoV-2 BA.1, BA.1.1 and BA.2 and the neutralizing activity of different monoclonal antibodies and sera against them.
- Sho Iketani
- , Lihong Liu
- & David D. Ho
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Article |
Structure of a B12-dependent radical SAM enzyme in carbapenem biosynthesis
X-ray crystal structures of TokK, a cobalamin- or B12-dependent radical SAM methylase, provide insight into how these enzymes use sequential radical-mediated methylations to assemble the C6 side chain of carbapenem antibiotics.
- Hayley L. Knox
- , Erica K. Sinner
- & Squire J. Booker
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Article
| Open Access
Emergence of methicillin resistance predates the clinical use of antibiotics
Methicillin-resistant strains of Staphylococcus aureus appeared in European hedgehogs in the pre-antibiotic era as a co-evolutionary adaptation to antibiotic-producing dermatophytes and have spread within the local hedgehog populations and between hedgehogs and secondary hosts.
- Jesper Larsen
- , Claire L. Raisen
- & Anders R. Larsen
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Article |
A naturally inspired antibiotic to target multidrug-resistant pathogens
The discovery and synthesis of a colistin congener provide a promising clinical lead against mcr-1-encoding colistin-resistant pathogens, which are responsible for an increasing number of deaths from antibiotic-resistant infections.
- Zongqiang Wang
- , Bimal Koirala
- & Sean F. Brady
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Research Briefing |
Bacterial drug resistance overcome by synthetic restructuring of antibiotics
Chemical synthesis, guided by crystal structures of antibiotics bound to the bacterial ribosome, has been used to discover a class of broad-spectrum antibiotics that overcomes bacterial multidrug resistance. Biochemical and crystallographic studies reveal the mechanism of action, including how one mode of resistance is circumvented.
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Article |
A synthetic antibiotic class overcoming bacterial multidrug resistance
Structure-guided design and component-based synthesis are used to produce iboxamycin, a novel ribosome-binding antibiotic with potent activity against Gram-positive and Gram-negative bacteria.
- Matthew J. Mitcheltree
- , Amarnath Pisipati
- & Andrew G. Myers
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Article |
Unravelling the collateral damage of antibiotics on gut bacteria
This study systematically profiles the activity of several classes of antibiotics on gut commensal bacteria and identifies drugs that mitigate their collateral damage on commensal bacteria without compromising their efficacy against pathogens.
- Lisa Maier
- , Camille V. Goemans
- & Athanasios Typas
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Technology Feature |
Innovative tools take aim at antibiotic-resistant microbes
Diagnostics that rely on bacterial movements, genomics and machine learning could help to address a global crisis.
- Jyoti Madhusoodanan
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Article |
Novel bile acid biosynthetic pathways are enriched in the microbiome of centenarians
The microbiota of centenarians (aged 100 years and older) comprise gut microorganisms that are capable of generating unique secondary bile acids, including isoallolithocholic acid, a bile acid with potent antimicrobial effects against Gram-positive—but not Gram-negative—multidrug-resistant pathogens.
- Yuko Sato
- , Koji Atarashi
- & Kenya Honda
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Editorial |
Funders, now is the time to invest big in COVID drugs
Vaccine development has been a resounding success. But the medicine cabinet should have been better stocked.
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Article |
The antibiotic darobactin mimics a β-strand to inhibit outer membrane insertase
Structural studies resolve how the antibiotic darobactin inhibits the bacterial BAM insertase.
- Hundeep Kaur
- , Roman P. Jakob
- & Sebastian Hiller
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Article |
Type III-A CRISPR immunity promotes mutagenesis of staphylococci
In Staphylococcus epidermidis and Staphylococcus aureus, non-specific DNase activity of the type III-A CRISPR–Cas system increases the rate of mutations in the host and accelerates the evolution of resistance to antibiotics and to phage.
- Charlie Y. Mo
- , Jacob Mathai
- & Luciano A. Marraffini
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News & Views |
RETRACTED ARTICLE: A two-pronged attack on antibiotic-resistant microbes
Isoprenoid molecules are essential in many disease-causing microorganisms, and intermediates made during their synthesis trigger immune-defence responses by γδ T cells. ‘Immunoantibiotics’ exploit this dual vulnerability.
- Youcef Mehellou
- & Benjamin E. Willcox
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Article |
Highly multiplexed spatial mapping of microbial communities
High-phylogenetic-resolution microbiome mapping by fluorescence in situ hybridization (HiPR-FISH) enables the spatial mapping of hundreds of species of microorganisms and shows how microbial networks in the mouse gut are affected by antibiotic treatment.
- Hao Shi
- , Qiaojuan Shi
- & Iwijn De Vlaminck
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Article |
Synthetic group A streptogramin antibiotics that overcome Vat resistance
Modular synthesis and structural biology are used to design and characterize group A streptogramin antibiotics, one of which has activity against streptogramin-resistant strains and demonstrates efficacy in a mouse model of bacterial infection.
- Qi Li
- , Jenna Pellegrino
- & Ian B. Seiple
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News Feature |
The antibiotic paradox: why companies can’t afford to create life-saving drugs
Paratek Pharmaceuticals successfully brought a new antibiotic to the market. So why is the company’s long-term survival in question?
- Maryn McKenna
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Article |
Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike
A diverse collection of potent neutralizing antibodies against the SARS-CoV-2 spike protein have been isolated from five patients with severe COVID-19 and high serum neutralization titres.
- Lihong Liu
- , Pengfei Wang
- & David D. Ho
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Article |
Decoy exosomes provide protection against bacterial toxins
In response to infection with Staphylococcus aureus in vitro and in vivo, host cells increase their secretion of exosomes containing ADAM10—vesicular structures that can provide protection by sequestering bacterial toxins.
- Matthew D. Keller
- , Krystal L. Ching
- & Ken Cadwell
Antibiotic resistance is a growing threat — is climate change making it worse?