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Comparative genomics and high-resolution mass spectrometry reveal the biosynthetic gene clusters, and vast chemical diversity of natural products that they encode, in Photorhabdus and Xenorhabdus, bacteria that interact with hosts as symbionts and entomopathogens.

Bacterial superantigens (sAg) have been shown to induce T cell hyperactivation through cross linking between MHC class II on antigen presenting cells and certain TCRs on T lymphocytes. Here the authors explore how sAg impacts CD4 and CD8 T cell subsets, leading to either expansion or excessive release of pro-inflammatory cytokines and they observe that a temporary state of anergy can occur, while bacterium-specific T cells continue to be generated

This study reveals how the pathogen Staphylococcus aureus adapts to the lung microenvironment, rich in host metabolites fumarate and itaconate, by using a key enzyme, FumC, to support its metabolic fitness, survival, and persistence.

Genomic evidence reveals that Mycobacterium ulcerans recovered from Aedes notoscriptus mosquitoes are genetically identical to bacteria from possums and humans, implicating mosquitoes as a vector for Buruli’s ulcer transmission in southeastern Australia.

Rifaximin use, particularly in patients with liver cirrhosis, may be compromising the clinical use of daptomycin.

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.

Genomic analysis uncovers global prevalence of three multidrug-resistant Staphylococcus epidermidis lineages encoding rifampicin resistance and reduced susceptibility to glycopeptide antibiotics.

WalKR is an essential two-component regulator that controls peptidoglycan synthesis in the human pathogen Staphylococcus aureus. Here, the authors provide biochemical, structural, and functional evidence supporting that the binding of a zinc ion inhibits autophosphorylation and thus alters WalKR regulatory activity.

Staphylococcus aureus upregulates collagenase and proline transporters to release collagen-derived proline and exploit fibroblasts as a nutrient source during chronic infection.

Vancomycin-resistant Enterococcus faecium is an important healthcare-associated pathogen and genomic analyses could inform targeted interventions. Here, the authors optimise an analysis pipeline for identification of putative transmission events using core genome multilocus sequence type clustering and split kmer analysis.

Mycobacterium kansasii can cause serious pulmonary disease. Here, the authors present a population genomics analysis of 358 environmental and clinical isolates from around the world, supporting the idea that municipal water is a main source of infection, and shedding light into the pathogen’s diversity and adaptation to the human host.

Humans contract Buruli ulcer following infection withMycobacterium ulcerans, a slow-growing toxin producer that evolved from Mycobacterium marinum. Both M. ulcerans and M. marinum are waterborne, but M. ulceransis associated with various insects that might serve as vectors. This Review summarizes recent findings and explains how the toxin, a polyketide called mycolactone, acts on immune cells.

Entomopathogenic nematodes carrying Xenorhabdus and Photorhabdus bacteria prey on insect larvae in the soil. Now, a comprehensive analysis of the bacterial genome has revealed ubiquitous and unique families of biosynthetic gene clusters. Evaluation of the bioactivity of the natural products expressed by the most prevalent cluster families explains the functional basis of bacterial natural products involved in bacteria–nematode–insect interactions.

The implementation of genomics for identification and surveillance of antimicrobial resistance (AMR) in clinical laboratories remains challenging. Here, Sherry et al. present a bioinformatics platform for detection of AMR determinants from whole-genome sequencing data, suitable for clinical and public-health microbiology reporting.

Regulatory small RNA (sRNA) interact with mRNAs to regulate their stability, transcription, and translation via diverse mechanisms. Here, Mediati et al. apply RNase III-CLASH to multidrug-resistant Staphylococcus aureus to characterise the network of RNA–RNA interactions associated with RNase III and identify a regulatory mRNA 3′UTR, named vigR-3′UTR, involved in the regulation of genes relevant for vancomycin sensitivity.

pks5-recombination-mediated cell surface remodelling increased virulence of Mycobacterium canettii, driving evolution from a putative generalist mycobacteria towards a professional pathogen of mammalian hosts.

Roland Brosch and colleagues report whole-genome sequencing of tubercle bacilli with smooth colony morphology, also known as Mycobacterium canetti and/or Mycobacterium prototuberculosis, obtained from humans with tuberculosis from geographically diverse regions. Their comparative genomic analysis with Mycobacterium tuberculosis and other M. tuberculosis complex members identifies extensive recombination and provides insights into the evolution of mycobacteria. The authors also report that tubercle bacilli with smooth colony morphology show reduced persistence and virulence compared to M. tuberculosis strains in infection experiments in mice.

Genome sequencing can be used to infer pathogen transmission dynamics and inform public health responses. Here, the authors sequence >1,200 SARS-CoV-2 samples from Victoria, Australia and find genomic support for the effectiveness of social restrictions in reducing transmission.

A small RNA regulates the production of metabolites with roles in symbiosis and virulence in Photorhabdus and Xenorhabdus.

In this Review, Howden and co-workers examine and integrate recent key advances in understanding the mechanisms that Staphylococcus aureus uses to cause infections.