Bacterial exotoxin

Buruli ulcer is an emerging chronic infectious skin disease caused by Mycobacterium ulcerans. Mycolactone, an exotoxin produced by the bacterium, is the only identified virulence factor so far, but the functions of this toxin and the mechanisms of disease progression remain unclear. By interfering Sec61 translocon, mycolactone inhibits the Sec61-dependent co-translational translocation of newly synthesized proteins, such as induced cytokines and immune cell receptors, into the endoplasmic reticulum. However, in regard to IL-1β, which is secreted by a Sec61-independent mechanism, mycolactone has been shown to induce IL-1β secretion via activation of inflammasomes...

Campylobacter remains the leading cause of bacterial foodborne illness in the U.S. and worldwide. Campylobacter plasmids may play a significant role in antimicrobial resistance (AMR) and virulence factor distribution, and potentially drive rapid adaptation. C. coli (n = 345) and C. jejuni (n = 199) isolates collected from live cattle, swine, turkey, and chickens, poultry carcasses at production, and retail meat in N.C. were analyzed to determine plasmid prevalence, extrachromosomal virulence and AMR genes, and the phylogeny of assembled plasmids...

Bacillus cereus endophthalmitis is a devastating eye infection that causes rapid blindness through the release of extracellular tissue-destructive exotoxins. The phagocytic and antibacterial functions of ocular cells are the keys to limiting ocular bacterial infections. In a previous study, we identified a new virulence gene, plcA-2 (different from the original plcA-1 gene), that was strongly associated with the plcA gene of Listeria monocytogenes. This plcA gene had been confirmed to play an important role in phagocytosis...

5-Lipoxygenase-activating protein (FLAP) is a regulator of cellular leukotriene biosynthesis, which governs the transfer of arachidonic acid (AA) to 5-lipoxygenase for efficient metabolism. Here, the synthesis and FLAP-antagonistic potential of fast synthetically accessible 1,2,4-triazole derivatives based on a previously discovered virtual screening hit compound is described. Our findings reveal that simple structural variations on 4,5-diaryl moieties and the 3-thioether side chain of the 1,2,4-triazole scaffold markedly influence the inhibitory potential, highlighting the significant chemical features necessary for FLAP antagonism...

In this issue of JEM, companion articles from Pinilla et al. (2023. J. Exp. Med.https://doi.org/10.1084/jem.20230104) and Robinson et al. (2023. J. Exp. Med.https://doi.org/10.1084/jem.20230105) demonstrate that ribotoxic stress induced by Pseudomonas aeruginosa and Corynebacterium diphtheriae EEF2-targeting exotoxins leads to NLRP1 inflammasome activation, representing a new mechanism of effector-triggered immunity.

The ZAKα-driven ribotoxic stress response (RSR) is activated by ribosome stalling and/or collisions. Recent work demonstrates that RSR also plays a role in innate immunity by activating the human NLRP1 inflammasome. Here, we report that ZAKα and NLRP1 sense bacterial exotoxins that target ribosome elongation factors. One such toxin, diphtheria toxin (DT), the causative agent for human diphtheria, triggers RSR-dependent inflammasome activation in primary human keratinocytes. This process requires iron-mediated DT production in the bacteria, as well as diphthamide synthesis and ZAKα/p38-driven NLRP1 phosphorylation in host cells...

Infections by Clostridioides difficile, a bacterium that targets the large intestine (colon), impact a large number of people worldwide. Bacterial colonization is mediated by two exotoxins: toxins A and B. Short peptides that can be delivered to the gut and inhibit the biocatalytic activity of these toxins represent a promising therapeutic strategy to prevent and treat C. diff. infection. We describe an approach that combines a Peptide Binding Design (PepBD) algorithm, molecular-level simulations, a rapid screening assay to evaluate peptide:toxin binding, a primary human cell-based assay, and surface plasmon resonance (SPR) measurements to develop peptide inhibitors that block Toxin A in colon epithelial cells...

Gram-positive organisms are known causative agents in toxic shock syndrome (TSS), an acute disease caused by bacterial exotoxins. During routine instrumentation removal for chronic osteomyelitis, intraoperative debridement, reaming, and irrigation can lead to cell lysis and subsequent dissemination of the bacterium exotoxin, which can result in acute cardiovascular compromise. We present two cases of chronic osteomyelitis in healed long-bone fractures that were treated with deep instrumentation removal and surgical debridement using a reamer-irrigator-aspirator (RIA) system...

Pseudomonas aeruginosa (PSAE) is known for its ability to form biofilm and produce other virulence factors associated with a resistant phenotype. Multidrug-resistant (MDR) PSAE strains represent a serious problem in healthcare and are the focus of an increasing number of studies dealing with the therapy of infections caused by these bacteria. Nowadays, a number of studies focus on the presence of virulence factors rather than on the mechanisms of resistance to the antibiotics used, as it is the study of virulence factors that makes it possible to expand the possibilities of effective and efficient therapy...

Pseudomonas aeruginosa is a pathogen capable of colonizing virtually every human tissue. The host colonization competence and versatility of this pathogen are powered by a wide array of virulence factors necessary in different steps of the infection process. This includes factors involved in bacterial motility and attachment, biofilm formation, the production and secretion of extracellular invasive enzymes and exotoxins, the production of toxic secondary metabolites, and the acquisition of iron. Expression of these virulence factors during infection is tightly regulated, which allows their production only when they are needed...

The vertebrate host's immune system and resident commensal bacteria deploy a range of highly reactive small molecules that provide a barrier against infections by microbial pathogens. Gut pathogens, such as Vibrio cholerae, sense and respond to these stressors by modulating the expression of exotoxins that are crucial for colonization. Here, we employ mass-spectrometry-based profiling, metabolomics, expression assays and biophysical approaches to show that transcriptional activation of the hemolysin gene hlyA in V...

Toxic shock syndrome (TSS) is a rare and life-threatening condition characterized by the systemic manifestation of severe infection. It is caused by exotoxin-producing strains of Staphylococcus aureus and Streptococcus pyogenes . Erythroderma, often described as generalized exfoliative dermatitis, is a rare and severe dermatological condition involving more than 90% of the body surface, identified as an uncommon cause of TSS. Here, we describe a case of a 72-year-old male who presented with signs and symptoms of erythroderma presenting as extensive erythematous scaling and lichenified plaques on multiple body surfaces and later developed TSS...

Recent advances in targeted cancer therapy hold great promise for both research and clinical applications and push the boundaries in finding new treatments for various currently incurable cancers. However, these therapies require specific cell-targeting mechanisms for the efficient delivery of drug cargo across the cell membrane to reach intracellular targets and avoid diffusion to unwanted tissues. Traditional drug delivery systems suffer from a limited ability to travel across the barriers posed by cell membranes and, therefore, there is a need for high doses, which are associated with adverse reactions and safety concerns...

Pseudomonas aeruginosa has assumed an increasingly prominent role as the aetiological agent in serious hard-to-treat infections in animals and humans. In this study, 271 P. aeruginosa strains collected from dogs and cats were investigated. The aim of the research was to screen these P. aeruginosa strains for antibiotic resistance and the presence of selected virulence factor genes. Antibiotic resistance was determined using the Kirby-Bauer method, while virulence genes were detected by polymerase chain reaction (PCR)...

Quorum sensing (QS) in Pseudomonas aeruginosa plays an essential role in virulence factors, biofilm formation as well as antibiotic resistance. Approaches that target virulence factors are known to be more sustainable than antibiotics in weakening the infectivity of bacteria. Although honey has been shown to exert antipseudomonal activities, the enhancement of such activity in ginger-enriched honey is still unknown. The main objective of this study was to determine the impacts of honey and ginger-enriched honey on the QS virulence factors and biofilm formation of antibiotic resistant P...

Ribosome-inactivating proteins (RIPs) are found in bacteria, fungi, and plants, with a wide range of biological resistances such as anti-fungal, anti-viral, anti-insect, and anti-tumor. They can be roughly divided into proactive defense bacterial or fungal types and passive defense plant types. We identified 1592 RIP genes in bacteria, fungi, and plants. Approximately 88 % of the 764 bacterial RIPs were Shiga or Shiga-like toxins which were exotoxins and could rapidly enter cells to possess strong biotoxicity, and about 98 % of fungal RIPs were predicted as secreted proteins...

BACKGROUND: According to gas chromatography - mass spectrometry (GC-MS) results of a previous study, six metabolites including alpha-terpineol, geranyl acetate, linalool, myrcenol, terpinolene, and thymol showed significantly more amount relative to other metabolites. METHODS: A continuation of the previous study, the interaction of these metabolites with the main virulence factors of P. aeruginosa (pseudomonas elastase and exotoxin A), Staphylococcus aureus (alpha-hemolysin and protein 2a), Mycobacterium tuberculosis (ESX-secreted protein B and the serine/threonine protein kinase), and Escherichia coli (heat-labile enterotoxin and shiga toxin) were evaluated by molecular docking study and molecular simulation...

BACKGROUND: Otitis externa and otitis media are two types of ear infections that affect people of all ages, although they are more common in newborns and young children. Antibiotic usage, healthcare, and advanced age all play a role in the development of this illness. METHODS: Fifty-eight patients with various kinds of infections of the ears were voluntary patients attending the outpatient clinics of the Prince Mutaib Bin Abdulaziz Hospital in Sakaka, Al Jouf, Saudi Arabia, examined to evaluate the role of bacteria and the likely significance of plasmids in their antibiotic resistance as ear infectious agents...

BACKGROUND: Streptococcus pyogenes (group A streptococci; GAS) is the main causative pathogen of monomicrobial necrotizing soft tissue infections (NSTIs). To resist immuno-clearance, GAS adapt their genetic information and/or phenotype to the surrounding environment. Hyper-virulent streptococcal pyrogenic exotoxin B (SpeB) negative variants caused by covRS mutations are enriched during infection. A key driving force for this process is the bacterial Sda1 DNase. METHODS: Bacterial infiltration, immune cell influx, tissue necrosis and inflammation in patient´s biopsies were determined using immunohistochemistry...

An effective vaccine against Pseudomonas aeruginosa would benefit people susceptible to severe infection. Vaccination targeting V antigen (PcrV) of the P. aeruginosa type III secretion system is a potential prophylactic strategy for reducing P. aeruginosa -induced acute lung injury and acute mortality. We created a recombinant protein (designated POmT) comprising three antigens: full-length PcrV (PcrV#1-#294 ), the outer membrane domain (#190-342) of OprF (OprF#190-#342 ), and a non-catalytic mutant of the carboxyl domain (#406-613) of exotoxin A (mToxA#406-#613(E553Δ) )...