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ABC toxins are bacterial insecticides with biotechnological potential. Here, Low et al. have deciphered soluble and membrane-inserted structures of YenTc that highlight structural and mechanistic diversity in the ABC toxin family and provide insights into their evolution.

Botulinum toxins vary in oral toxicity, but the reasons are unclear. Here, the authors show that the differences can be due to variations in one of the toxin’s components, the hemagglutinin complex, which influence mucin binding and mucus layer penetration

Diphtheria is an infectious disease caused by toxigenic strains of Corynebacterium diphtheriae. The molecular and geographical epidemiology of the bacteria is constantly evolving and, together with decreased vaccination coverage, could promote the re-emergence of this disease.

Mycobacterium tuberculosis uses five ESX systems to secrete multiple effector proteins that are essential for the pathogen’s growth and virulence. Here, Nair et al. identify a protein complex that is required for outer-membrane localization and for secretion of all ESX-dependent proteins into the cytosol of infected macrophages.

Here, the authors show that hepatic lipid accumulation induced by Helicobacter hepaticus involves mitochondrial dysfunction and disrupted lipid metabolism via CdtB-ROS-mTORC1-SREBP1 and NONO, highlighting CdtB as a key mediator and potential therapeutic target.

Lymphostatin is a large protein required for Escherichia coli virulence. Here, Griessmann et al. use electron cryo-microscopy to describe the structure of lymphostatin determined at different pH values, showing three conformations, six distinct domains, and long inter-domain linkers that occlude the catalytic sites of the N-terminal glycosyltransferase and protease domains.

Bacteria produce antibacterials to aid competition in complex communities. Here, the authors show that class II microcins, an understudied group of secreted antibacterials, are abundant, with diverse sequences and antibacterial characteristics.

Oral vaccines against Vibrio cholera have been critical for cholera management, but the production of more efficacious and cost-effective approaches is still needed. Here the authors deliver a bivalent V_HH construct that binds to cholera toxin and show protection in a murine cholera model.

Toxin-antitoxin (TA) systems are common in bacteria and archaea and contribute to phage defense. Here, the authors structurally and biochemically characterize a new anti-phage TA system, ShosTA.

The bacterial pathogen Legionella pneumophila is known to regulate a wide spectrum of host processes using its Dot/Icm effectors. In this work, He et al. provide insight into L. pneumophila regulation of ATP level in host cells.

In this Review, Basler and colleagues examine the type VI secretion system (T6SS), focusing on the diversity of antibacterial T6SS effectors and the evolutionary forces that shape them. They explain how effectors diversify and highlight interbacterial antagonism as a key driver of this process.

The potential roles of post-translational modification of bacterial proteins in pathogenesis are not well understood. Here, Wang et al. show that posttranslational lactylation of proteins, in particular alpha-toxin, is important for virulence of the human pathogen Staphylococcus aureus.

HEPN–MNT is a bacterial type VII toxin-antitoxin (TA) system, comprising the HEPN toxin and the MNT antitoxin. Crystal structures and functional assays of the HEPN–MNT module suggest that HEPN is a metal-dependent RNase and identify its active site residues and regulatory mechanism.

Chen et al. probe the role of a genotoxin of Salmonella typhi in triggering a senescence-associated secretory phenotype, via mitochondrial DNA damage.

Clostridium difficile, an important nosocomial pathogen, produces two toxins. Studies with purified toxins have indicated that only toxin A is important for pathogenesis, but recently it has been suggested that toxin B causes the majority of the disease symptoms in the context of a bacterial infection. These authors demonstrate that both toxins are important for disease and will need to be considered for diagnosis and treatment.

Xinchen Lv and colleagues design pan-specific protein mini-binders that neutralize Clostridioides difficile toxin B (TcdB) and solve TcdB-binder complex structures via cryo-electron microscopy.

Thioredoxin 1 (TrxA) is an enzyme that reduces disulfide bonds in the bacterial cytosol. Here, the AUs show that TrxA can function as a chaperone of the secreted bacterial ADP-ribosyltransferase toxin TreX independent of redox catalysis.

Paeniclostridium sordellii hemorrhagic toxin (TcsH) targets TMPRSS2 to enter the host cells. Here, authors showed the cryo-EM structures of the TcsH-TMPRSS2 complex, providing a toxin-receptor interaction model for large clostridial toxins.

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.

Staphylococcus aureus produces pore-forming toxins, such as α-hemolysin, that damage epithelial cell layers, causing disease. In this issue, Inoshima et al. report that the cellular receptor for α-hemolysin—the metalloprotease ADAM10—is essential for lethal pneumonia caused by S. aureus infection in mice. The authors suggest that the combined effect of α-hemolysin on pore formation and in activating ADAM10 cleavage of the adherens junction protein E-cadherin disrupts the barrier function of the lung epithelium.

Bacteria can secrete diffusible protein toxins that kill competing bacteria. Here, the authors use biochemical, biophysical and structural analyses to show how one of these toxins exploits TolC (a major antibiotic efflux channel) to transport itself across the outer membrane of target cells.

Enterococcus strains harbour a plasmid-encoded defence against reuterin, a toxin produced by Limosilactobacillus reuteri, mediating a mutualistic metabolic interaction between these two gut microbiota members.

Paeniclostridium sordellii lethal toxin (TcsL) is a potent toxin that can cause toxic shock syndrome. TcsL contains a unique CROPs domain with unclear functions. Here, the authors provide evidence of the CROPs domain’s role in stability and toxicity of TcsL.

Bacteria often produce antimicrobial toxins to compete in microbial communities. Here, the authors identify a family of peptide toxins that are produced by, and target, Bacteroidetes species, some of which are widespread in the human gut microbiota.

Bacteria harness toxin-antitoxin systems to manipulate growth and evade stress. Using biochemistry, biophysics, and crystallography, the authors characterize a mechanism of antitoxin-induced autophosphorylation that can neutralize nucleotidyltransferase toxins of Mycobacterium tuberculosis.

Bacteria use the type VI secretion system (T6SS) to deliver toxic effectors into bacterial or eukaryotic cells. Here, Kanarek et al. identify a protein domain, RIX, that defines a class of polymorphic T6SS effectors with antibacterial and anti-eukaryotic toxic domains, and that enables T6SS-mediated delivery of other effectors.

Pathogenic bacteria produce cholesterol-dependent cytolysins to form pores in eukaryotic membranes. Here, the authors show that human gut bacteria use a related family of pore-forming toxins for intra- and interspecies antagonism.

Klebsiella oxytoca provides protection against Salmonella Typhimurium via toxin-dependent inhibition in nutrient-rich, low-competition environments but switches to substrate-driven competition when nutrients are limited.

Paeniclostridium sordellii is an opportunistic pathogen that can occur and be fatal in women undergoing abortion or childbirth. The pathogenesis of a hemorrhagic toxin, TcsH, produced by this bacteria, remains unknown. Here, authors carry out genome-wide screens to identify pathologically relevant host factors of TcsH.

Antimicrobial toxins are secreted by bacteria to kill rival species. Here the authors report the mechanism of inhibition of EsaD, a toxin secreted by some S. aureus strains to kill competitors that lack the antitoxin EsaG, showing marked mechanistic differences to other Type II toxin-antitoxin systems.

Binary toxin translocation system consists of an enzymatic subunit and translocation pore. Here, the authors report the high-resolution cryo-EM structure of Clostridioides difficile binary toxin, comprising ADP-ribosyltransferase CDTa bound to the CDTb pore and revealing translocational unfolding of CDTa in the CDTb-pore.

The pathophysiological mechanism of venous thrombosis associated with Vibrio vulnificus infection remains largely unknown. In this work, the authors investigate this association, focusing on effects of the pore-forming MARTX toxin of V. vulnificus on red blood cells, and the utilisation of a rat venous thrombosis model.

Bacteria can deliver toxic effector proteins into the cytosol of neighboring cells. Here, the authors show that Yersinia pseudotuberculosis secretes an effector that modulates gene expression in neighboring cells of the same species and inhibits the growth of other competitors.

Toxin B (TcdB) is a major exotoxin responsible for diseases associated with C. difficile infection. Here, Tian et al. show that several TcdB subtypes do not recognize the established FZD receptors, and identify a different host protein (TFPI) as a receptor for subtypes TcdB4 and TcdB10.

The bacterium Phocaeicola vulgatus is commonly found in the human gut. Here, the authors show that the microorganism produces an antibacterial toxin that targets the LPS core glycan of closely related species and induces a response that partially protects cells from multiple antimicrobial toxins.

An environmentally safe means of mosquito control is the application of Bacillus thuringiensis israelensis, which produces a cocktail of four naturally crystalline proteins exclusively toxic to mosquito. Here the authors report the atomic-resolution structures of Bti Cry11Aa and related Btj Cry11Ba solved de novo through Serial Femtosecond Crystallography on naturally-occurring nanocrystals.

The pathogen Legionella pneumophila mediates NAD⁺-dependent ubiquitination pathways upon infection. Here, the authors show the Legionella effector MavL reverses ubiquitin ADP-ribosylation to regulate these pathways. MavL represents a new macrodomain class specific for reversal of arginine ADP-ribosylation with distinct ADP-ribose binding features.

Streptomyces are discovered to produce antibacterial protein complexes that selectively inhibit the hyphal growth of related species, a function distinct from that of the small-molecule antibiotics they are known for.

The tuberculosis necrotizing toxin (TNT) is the major cytotoxicity factor of M. tuberculosis (Mtb). Mtb possesses five type VII secretion systems (ESX). Pajuelo et al. show that the ESX-4 system is required for TNT secretion and that ESX-2 and ESX-4 systems work in concert with ESX-1 to permeabilize the phagosomal membrane and enable trafficking of TNT into the cytoplasm of macrophages infected with Mtb.

Type-III secretion systems (T3SSs) are capable of translocating proteins with high speed while maintaining the membrane barrier for small molecules. Here, a structure-function analysis of the T3SS pore complex elucidates the precise mechanisms enabling the gating and the conformational changes required for protein substrate secretion.

Bacteria can use type VI secretion systems (T6SSs) to inject toxic effector proteins into adjacent cells, in a contact-dependent manner. Here, the authors provide evidence of contact-independent killing by a T6SS effector that is secreted into the extracellular milieu and then taken up by other bacterial cells.

Rearrangement hot spots (Rhs) proteins are bacterial polymorphic toxin systems. Here, the authors show that Rhs1 forms a complex with the Type VI secretion system (T6SS) spike protein VgrG and the EagR chaperone. They also present the cryo-EM structure of the Rhs1-EagR complex and propose a model for Rhs loading and delivery by the T6SS.

Cases of diphtheria have increased in recent years. Here, the authors analyse the genomes of 502 Corynebacterium diphtheriae isolates across 16 countries and territories over 122 years, describing an increase in antimicrobial resistance genes and identifying toxin variants.

Coagulase-negative staphylococci and Staphylococcus aureus colonize similar niches in mammals. Here, Chin et al. show that a coagulase-negative staphylococcus secretes 6-thioguanine, a purine analog that suppresses S. aureus growth and virulence by inhibiting de novo purine biosynthesis and toxin production.

Rhs proteins delivered by the Type VI secretion system play a key role in competition between rival bacteria. Here, the authors show that Rhs proteins with exchangeable NAD(P)⁺ glycohydrolase toxin domains and ‘orphan’ immunity proteins are flexible agents of intraspecies competition in Serratia.

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.

Structural and functional characterization of an NF-κB-targeting bacterial toxin reveals an unconventional structure and mechanisms of membrane interaction and translocation.

Here Garrett et al. describe a toxin, TslA, secreted by type VII secretion system that has a reverse domain arrangement compared to other previously characterised substrates. The authors show that TslA is a lipase with antibacterial activity.

Bacterial Rhs proteins constitute a diverse family of secreted toxins. Here, the authors present a cryo-electron microscopy structure of an Rhs protein from Pseudomonas aeruginosa and provide insights into the mechanisms by which the protein delivers its encapsulated pore-forming toxin fragment to the bacterial membrane.

The greater wax moth (GWM) is a major bee pest. Here, the authors show how a pest control method that combines a strain of Bacillus thuringiensis and a lure-based entrapment can help to control GWM using lab experiments and field beehives.