Getting acquainted with npj Antimicrobials and Resistance

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.

There is an urgent need for novel strategies to combat life-threatening fungal infections. Here, Revie et al. identify a compound that induces alterations in fungal membranes, synergizes with azole antifungals against the pathogen Candida albicans, and inhibits virulence traits and biofilm formation in animal models of infection.

Current treatments for toxoplasmosis are limited by adverse reactions and inability to cure chronic infections dominated by semi-dormant cyst forms. Here the authors demonstrate the potential of small molecule inhibitors of PheRS for controlling acute and chronic toxoplasmosis.

Rational design of live-attenuated RNA viruses with potential as vaccines is enabled by identification of sequence rules for zinc finger antiviral protein.

Eller et al. develop a Facile Accelerated Specific Therapeutic (FAST) platform of antisense therapeutics that targets MDR bacterial pathogens with peptide nucleic acids (PNAs). This platform designs species and/or sequence specific PNAS based on a bioinformatics toolbox and offers a new delivery approach by repurposing the bacterial Type III secretion system in conjunction with a kill switch to overcome limited transport of PNAs into mammalian cells.

Malaria parasite heme pathway is non-essential for blood stages, but essential for mosquito and liver stages. Here, the authors show that heme pathway promotes cerebral pathogenesis by enhancing hemozoin formation and that targeting it with griseofulvin inhibits cerebral malaria in mice.

In this Review, Blair, Webber and colleagues explore our understanding of the mechanisms of antibiotic resistance, including reduced permeability, antibiotic efflux, modification or alteration of the antibiotic target, modification or destruction of the drug itself, and bypass of metabolic pathways. They also discuss how this information can aid in developing the next generation of antimicrobial therapies.

SCCmec is a large mobile genetic element that confers resistance to β-lactam antibiotics in methicillin-resistant Staphylococcus aureus. Here, the authors show that biofilm growth conditions enhance the efficiency of natural transformation in S. aureus and allow the transfer of SCCmec to methicillin-sensitive strains.

The host environment can impact the outcomes of antimicrobial therapies through unclear mechanisms. Here, Ledger et al. show that human serum reduces the efficacy of the antibiotic daptomycin against Staphylococcus aureus by inducing specific pathways leading to changes in the composition of the bacterial membrane and cell wall.

The impacts of fungal infections on human health are of increasing concern, and resistance of pathogenic fungi to all licensed systemic antifungals has been documented. In this Review, Fisher, Verweij and colleagues discuss the research and innovation topics that are needed to understand and minimize the occurrence and impact of antifungal resistance.

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.

A lack of understanding in the development and emergence of antimicrobial resistance presents as a problem for accurate infection diagnosis and treatment. Here, authors utilize Streptococcus pneumoniae and build a genome-wide atlas to understand the genes and interactions that contribute to altered drug susceptibility.

Here the authors present KIDS, a knowledge graph integration and phenotypic prediction framework. When applied on antibiotic data, it identifies 6 novel antibiotic resistant E. coli genes that the authors subsequently validate.

In this paper the authors show that the pathogenic bacterium Pseudomonas aeruginosa migrates between the gut and lungs of an ICU patient, and that differential evolutionary responses to antibiotic treatment occur in these organs.

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.

A combination of analysis of plasmid diversity in the gut of hospitalized patients with experimental evolution shows that the evolution of plasmid-mediated antibiotic resistance involves a trade-off between antibiotic resistance levels and bacterial fitness.

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.

Pathogens are typically classified as ‘antibiotic-resistant’ for clinical purposes based on cut-off values of minimum inhibitory concentrations (MICs). In this study, the authors explore quantitative values of MICs using the global ‘ATLAS’ database of pathogen-antibiotic pairs, describe trends in resistance, and compare results to other antibiotic resistance surveillance data.

Shigella sonnei is a major contributor to the global burden of dysenteric diarrhoea in developed countries. In this work, authors report a S. sonnei clone which has caused numerous waterborne shigellosis outbreaks in China from 2015 to 2020.

This Perspective discusses the emergence and connectedness of antimicrobial resistance across One Health and Global Health levels, as well as potential strategies for mitigating the burden of such resistance in human and environmental health.

Antibiotic use in livestock and aquaculture production is driving resistance to medically important antibiotics. Producing meat through alternative methods, such as cultivated meat, offers an opportunity to decouple antibiotics from meat.

Genomic analyses reveal Escherichia coli samples from livestock in China have a third more plasmids than 50 years ago, contributing to the spread of antimicrobial resistance.

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.

The putative causal agent of citrus greening Candidatus Liberibacter asiaticus (CLas) cannot be cultured, which hampers finding new therapies to control this devastating disease. Here, the authors show that hairy roots support CLas propagation and enable high throughput antimicrobial screening.