Search Results (221)

Shiga toxin-producing Escherichia coli (STEC) is a major zoonotic foodborne pathogen associated with severe human illnesses, including hemorrhagic colitis and hemolytic uremic syndrome. While ruminants are traditionally recognized as the primary reservoirs, increasing evidence suggests that poultry production systems may also contribute to the dissemination of pathogenic and antimicrobial-resistant E. coli through the food chain. However, the extent of this contribution and its relevance to human infection remain incompletely understood. This review provides a critical synthesis of the virulence mechanisms, epidemiology, and antimicrobial resistance (AMR) of E. coli, with particular emphasis on STEC in poultry production systems. Key virulence determinants, including Shiga toxins (Stx1 and Stx2), the locus of enterocyte effacement, and plasmid-encoded factors, are discussed in relation to their roles in host colonization and disease progression. Transmission pathways within poultry production and processing environments are examined, highlighting critical points of contamination from farm to consumer. The increasing prevalence of multidrug-resistant and extended-spectrum β-lactamase-producing E. coli in poultry underscores significant public health concerns. However, variability in epidemiological data and limitations in current surveillance systems complicate the interpretation of transmission dynamics. Current and emerging control strategies, including biosecurity measures, alternative antimicrobial interventions, and processing hygiene, are evaluated alongside their practical limitations under commercial conditions. Overall, this review identifies key knowledge gaps and emphasizes the need for integrated, evidence-based approaches within a One Health framework to better define zoonotic risks and develop sustainable control strategies. Full article

Background/Objectives: Atypical hemolytic uremic syndrome (aHUS) is a rare, life-threatening thrombotic microangiopathy caused by dysregulation of the alternative complement pathway, often related to genetic mutations or autoantibodies. The introduction of complement C5 inhibitors, such as eculizumab and ravulizumab, has significantly improved renal and overall outcomes. However, complement inhibition impairs host defense against encapsulated bacteria, markedly increasing the risk of invasive infections, particularly Neisseria meningitidis. Vaccination against meningococcal groups ACWY and B, along with temporary antibiotic prophylaxis, is therefore recommended before initiating anti-C5 therapy. Methods: We report the clinical course of a 13-year-old boy with aHUS secondary to anti–complement factor H (CFH) autoantibodies and CFHR3–CFHR1 homozygous deletion, treated with C5 inhibitors. Results: Despite complete meningococcal vaccination and a previous course of antibiotic prophylaxis, the patient developed meningitis during ongoing complement inhibitor therapy. Conclusions: This case highlights that breakthrough invasive infections may occur despite adherence to recommended preventive strategies. It underscores the need for sustained clinical vigilance, timely vaccine boosters, and careful reassessment of the risk–benefit balance of continued complement inhibition therapy. Full article

The complement system is the primary defense mechanism against pathogens, acting through opsonization, the membrane attack complex, and classical, lectin, or alternative pathways. These pathways result in the production of key complement components, including C3a (complement component), C5a, and C3b, which recruit inflammatory cells. Complement dysregulation leads to renal disease through the overproduction of anaphylatoxins or inappropriate formation of the membrane attack complex. The levels of complement components have been shown to be useful as predictive markers in acute kidney injury, especially in conditions of alternative pathway activation, and in diseases of immune complex pathology such as lupus nephritis and IgA nephropathy. Genetic defects in complement regulatory proteins result in diseases such as C3 glomerulopathy or atypical hemolytic uremic syndrome, in which uncontrolled C3 convertase activity results in renal failure. Therapeutic interventions targeting complement components, including eculizumab or pegcetacoplan, improve patient outcomes in atypical hemolytic uremic syndrome and C3 glomerulopathy, respectively, while other interventions improve renal function in IgA nephropathy. These findings underscore the dual role of the complement system, which is not only implicated in the progression of renal diseases but also provides the potential for the development of therapeutic interventions for the treatment of various forms of nephropathy. Full article

Phage-encoded Shiga toxin (Stx) released by Shiga toxin-producing E. coli (STEC) can kill multiple eukaryotic bacterial predators, including Acanthamoeba castellanii, Tetrahymena thermophila and Caenorhabditis elegans. However, the impact of Stx type, Stx amount, and the serogroup of the E. coli on the effectiveness of this exotoxin are poorly understood. These factors impact the severity of Stx-mediated disease in humans and therefore, by studying their role in modulating predator–prey interactions, we may gain insight into how these virulence factors evolved to contribute to human pathogenicity. Herein, we investigated the effects of these factors on predator killing by measuring the efficiency with which five different hemolytic uremic syndrome (HUS)-causing STEC strains consume and/or kill A. castellanii and C. elegans. These strains express various combinations of Stx types and amounts and O-antigens. We found that variations in Stx types and amounts significantly affect the ability of a given bacterial strain to kill predator A. castellanii and C. elegans, with higher Stx1 titers (HUSEC 31 vs. 19) and the presence of Stx2 alone (HUSEC 20) correlating with significantly greater predator killing. These attributes also affect STEC pathogenicity in humans, suggesting that ecological selective pressures for anti-predator defense inadvertently drive the evolution of strains with higher virulence potential in humans. Full article

Background: Shiga toxin (Stx), produced by enterohemorrhagic Escherichia coli (EHEC), is a highly potent exotoxin responsible for severe complications such as hemolytic uremic syndrome (HUS). Among its isoforms, Stx2 exhibits stronger cytotoxicity and poses greater clinical risk, yet no effective therapy currently exists. Methods: In this study, two human monoclonal antibodies, YG12-1 and YG12-2, were identified from a phage display library and systematically characterized using an integrated modeling–validation workflow. Results: Structural modeling with ImmuneBuilder and Rosetta revealed that YG12-2 possessed a longer CDRH3 topology, more short-range hydrogen bonds, and stronger electrostatic complementarity, corresponding to lower binding energy and higher apparent affinity in ELISA and SPR. Although YG12-2 had a better affinity, YG12-1 shows better protective activity in a murine model of acute peritoneal infection. This paradox highlights a non-linear relationship between structural affinity and biological efficacy, emphasizing the importance of functional epitope accessibility and pharmacokinetic behavior in determining neutralization outcomes. Conclusions: Overall, these results indicated that targeting Stx2 with YG12-1 and YG12-2 could serve as a promising protective strategy against E. coli O157:H7 infection. Full article

Therapeutic antibodies have revolutionized hematology, offering targeted and effective treatments for both malignant and non-malignant diseases. In hematologic malignancies, anti-CD20, anti-CD19, anti-CD38, and anti–B-cell maturation antigen (BCMA) antibodies have markedly improved survival outcomes, whereas antibody–drug conjugates and bispecific antibodies continue to expand therapeutic possibilities. Besides cancer, complement inhibitors such as eculizumab, ravulizumab, and the recently approved crovalimab have redefined paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome management, and the bispecific antibody emicizumab has transformed prophylaxis in hemophilia A. Furthermore, novel antibody formats such as the trifunctional anti-CD38 × CD3 antibody (Tri-31C2) exhibit enhanced anti-myeloma activity compared to chimeric CD38 antibodies, underscoring the future potential of T-cell–redirecting designs. This review summarizes key developments in therapeutic antibodies for hematological disorders, their action mechanisms, and emerging strategies to further optimize their efficacy and safety. Full article

Shiga toxin-producing Escherichia coli (STEC) is a major foodborne pathogen, responsible for severe gastrointestinal disease and hemolytic uremic syndrome (HUS). Here, we report Click Detect, a novel diagnostic platform that leverages click display to efficiently produce sensing probes for sandwich-style antigen detection. Click display is an in vitro protein display technology that generates uniform and covalently linked protein–cDNA conjugates in a simple one-pot reaction format within 2 h. The captured sensing probe can be quantified by standard nucleic acid amplification assays. Using click displayed DARPin (D_#20) as the sensing probe and a high-affinity nanobody (N_G1) as the capture reagent, Click Detect reliably detected Shiga toxin 2 (Stx2) at 600 fM by quantitative PCR (qPCR) and 6 pM by loop-mediated isothermal amplification (LAMP). The assay maintained comparable sensitivity in matrices containing up to 40% public swimming pool water or lettuce extract, highlighting robustness for real-world surveillance applications. Key advantages of Click Detect include simple, rapid, and cost-effective (~USD 0.04 per assay) sensing probe preparation, as well as a versatile plug-and-play probe format for detecting other targets. We believe that Click Detect has great potential as a novel sensing platform for food/environmental monitoring and point-of-care diagnostics, with potentially broad applicability to other toxins and protein targets. Full article

Background/Objectives: Hemolytic uremic syndrome is a thrombotic microangiopathy characterized by hemolytic anemia, thrombocytopenia, and acute kidney injury. Liver involvement in pediatric hemolytic uremic syndrome is increasingly recognized, but its clinical significance remains unclear. This study aimed to evaluate the relationship between liver involvement and clinical outcomes in children with hemolytic uremic syndrome. Methods: We retrospectively analyzed 25 pediatric patients diagnosed with hemolytic uremic syndrome. Patients were grouped based on liver involvement, defined by elevated transaminase levels. Demographic, clinical, laboratory, and treatment data were collected. Associations between liver involvement, intensive care unit admission, dialysis, plasma exchange, and length of intensive care unit stay were assessed using statistical analyses. Results: Liver involvement was observed in 68% of patients. Although liver involvement was not associated with the need for dialysis, affected patients required plasma exchange and intensive care unit admission significantly more often. An AST cutoff of ≥42 U/L moderately predicted adverse outcomes (AUC: 0.619), while ALT had limited prognostic value (AUC: 0.658). Transaminase levels normalized within a mean of 3.76 ± 1.92 days. No mortality was observed in our cohort, in contrast to previously reported rates of 2–5%. Conclusions: Liver involvement in pediatric hemolytic uremic syndrome is common but generally follows a reversible and benign course. While it is associated with increased intensive care unit admission and plasma exchange, it does not independently predict disease severity. These findings emphasize the importance of supportive management and suggest that liver involvement should be interpreted in the context of the overall clinical picture. Full article

The Shiga toxin-producing strain of Escherichia coli with serotype O157:H7 can cause acute bloody diarrhea, which can lead to life-threatening hemolytic uremic syndrome. According to the World Health Organization, this bacterium causes 2.8 million cases annually. Therefore, this theoretical study based on molecular docking and dynamics examined the inhibitory capacity of a series of aza-heterocyclic derivatives against the effector protein NleL of enterohemorrhagic E. coli (PDB ID: 3NAW), by determining affinity energy, stability, H-bond interactions and binding free energies of the compounds. The results obtained have enabled the identification of compounds with the potential to inhibit this infectious strain, contributing to an understanding of this protein. Full article

Microbial growth in food represents a public health problem that requires immediate attention. In Ecuador, 8924 cases of foodborne illness (FBD) were reported in 2020, most of them caused by bacteria. It is estimated that Escherichia coli causes 2,801,000 acute illnesses per year and results in 3890 cases of hemolytic uremic syndrome, 270 cases of end-stage renal disease and 230 deaths. Under this context, in this work, alginate capsules containing bioactive compounds from Lactobacillus plantarum GP108 were developed and their antimicrobial effect against E.coli was measured. The formulation of the capsules was carried out using a completely randomized experimental design with three formulations: maximum, average and minimum. The antimicrobial activity was measured by in vitro tests based on the increase in optical density during 7 days of exposure of E. coli with the capsules. By analysis of variance (ANOVA), it was found that the percentage inhibition of the capsules depended only on the formulation (p-value < 0.05), but not on the number of exposure capsules (p-value > 0.05). Tukey’s test indicated that the average formulation is the best at inhibiting the growth of E. coli, maintaining an average of 11.66% inhibition for 7 days. These findings show that bioactive compounds produced by L. plantarum GP108 encapsulated in alginate could be of potential use for food biopreservation. Full article

Background: Pregnancy-Related Acute kidney injury (PRAKI) is a critical complication of pregnancy, defined by the sudden deterioration in renal function during gestation or within the initial six weeks postpartum. Pregnancy is thought to increase the risk of acute kidney injury (AKI) by 51%. This is linked to the anatomical alterations that occur during pregnancy and special conditions, such as preeclampsia/eclampsia. PRAKI’s epidemiology and outcome vary between developed and developing nations. PRAKI is an uncommon entity in high-income countries; however, its incidence has recently increased. The aim of this systematic review is to evaluate the maternal and perinatal outcomes and risk factors affecting pregnancies affected by AKI. Methods: Comprehensive research was performed in PubMed/Medline, Scopus, and Google Scholar electronic databases from 2015 up to January 2025, using the terms AKI, PRAKI, sepsis, preeclampsia/eclampsia, liver enzymes, low platelet count (HELLP) syndrome, and pregnancy. After a thorough assessment, 25 full-text articles were obtained. Results: Our results revealed that preeclampsia, eclampsia, HELLP syndrome, and antepartum and postpartum hemorrhage predispose women to PRAKI. Other unusual factors, like disseminated intravascular coagulation (DIC) or hemolytic uremic syndrome (HUS), should not be underestimated. Furthermore, the latest published data showed unfavorable maternal and fetal outcomes in pregnancies affected by AKI compared to the general population. Conclusions: PRAKI constitutes a serious pregnancy complication that requires immediate treatment. The higher prevalence of PRAKI in developing countries (4–26%) versus wealthy nations (1.0–2.8%) has considerably indicated the impact of socioeconomic status and the accessibility of health services. Full article

Background: While most Escherichia coli strains are harmless members of the gastrointestinal microbiota, certain pathogenic variants can cause severe intestinal and extraintestinal diseases. A notable outbreak of E. coli O104:H4, involving both enteroaggregative (EAEC) and enterohemorrhagic (EHEC) strains, occurred in Europe, resulting in symptoms ranging from bloody diarrhea to life-threatening colitis and hemolytic uremic syndrome (HUS). Since treatment options remain limited and have changed little over the past 40 years, there is an urgent need for an effective vaccine. Such a vaccine would offer major public health and economic benefits by preventing severe infections and reducing outbreak-related costs. A multiepitope vaccine approach, enabled by advances in immunoinformatics, offers a promising strategy for targeting HUS-causing E. coli (O104:H4 and O157:H7 serotypes) with minimal disruption to normal microbiota. This study aimed to design an immunogenic multiepitope vaccine (MEV) construct using bioinformatics and immunoinformatic tools. Methods and Results: Comparative proteomic analysis identified 672 proteins unique to E. coli O104:H4, excluding proteins shared with the nonpathogenic E. coli K-12-MG1655 strain and those shorter than 100 amino acids. Subcellular localization (P-SORTb) identified 17 extracellular or outer membrane proteins. Four proteins were selected as vaccine candidates based on transmembrane domains (TMHMM), antigenicity (VaxiJen), and conservation among EHEC strains. Epitope prediction revealed ten B-cell, four cytotoxic T-cell, and three helper T-cell epitopes. Four MEVs with different adjuvants were designed and assessed for solubility, stability, and antigenicity. Structural refinement (GALAXY) and docking studies confirmed strong interaction with Toll-Like Receptor 4 (TLR4). In silico immune simulations (C-ImmSim) indicated robust humoral and cellular immune responses. In Conclusions, the proposed MEV construct demonstrated promising immunogenicity and warrants further validation in experimental models. Full article

Hemolytic uremic syndrome (HUS), a thrombotic microangiopathy primarily affecting the kidneys, can also involve the central nervous system (CNS), often leading to significant morbidity and mortality. Neurologic manifestations are among the most severe extra-renal complications, particularly in children and during outbreaks of Shiga toxin-producing Escherichia coli (STEC)-associated HUS (typical (tHUS)). This review explores the clinical spectrum, pathophysiology, diagnostic workup, and age-specific outcomes of neurologic involvement in both typical (tHUS) and atypical (aHUS). Neurologic complications occur in up to 11% of pediatric and over 40% of adult STEC-HUS cases in outbreak settings. Presentations include seizures, encephalopathy, focal deficits, movement disorders, and posterior reversible encephalopathy syndrome (PRES). Magnetic resonance imaging (MRI) commonly reveals basal ganglia or parieto-occipital lesions, though subtle or delayed findings may occur. Laboratory workup typically confirms microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and kidney damage, with additional markers of inflammation or metabolic dysregulation. Eculizumab is the first-line treatment for aHUS with CNS involvement, while its utility in STEC-HUS remains uncertain. Although many children recover fully, those with early CNS involvement are at greater risk of developing epilepsy, cognitive delays, or fine motor deficits. Adults may experience lingering neurocognitive symptoms despite apparent clinical recovery. Differences in presentation and imaging findings between age groups emphasize the need for tailored diagnostic and therapeutic strategies. Comprehensive neurorehabilitation and long-term follow-up are crucial for identifying residual deficits. Continued research into predictive biomarkers, neuroprotective interventions, and standardized treatment protocols is needed for improving outcomes in HUS patients with neurological complications. Full article

Background/Objectives: The field of nephrology is increasingly embracing advanced treatments and clinical trials that focus on inhibiting specific components of the complement cascade, a key driver in complement-mediated kidney diseases. Materials and Methods: This review aims to summarize innovative therapies targeting various pathways, including the inhibition of the terminal part of the complement pathway (mainly C5), the alternative pathway (factor B inhibitors), and the lectin pathway (MASP inhibitors. C5 inhibitors play a critical role in preventing the formation of the membrane attack complex (MAC), offering effective solutions for conditions like atypical hemolytic uremic syndrome (aHUS) and paroxysmal nocturnal hemoglobinuria (PNH). Meanwhile, avacopan, a C5a receptor antagonist, addresses ANCA-associated vasculitis (AAV) by mitigating inflammation and enabling reduced reliance on corticosteroids. Similarly, narsoplimab, which inhibits MASP-2, targets the lectin pathway implicated in conditions such as aHUS. Iptacopan, a factor B inhibitor, focuses on the alternative pathway and demonstrates efficacy in managing C3 glomerulopathy (C3G). Results: A systematic review of complement-targeted therapies was conducted, analysing studies from 2013 to 2023 that address unmet medical needs in primary and secondary glomerular diseases. Conclusions: Our systematic review of complement-targeted therapies shows that these tailored and innovative treatments may specifically address unmet medical needs in primary and secondary glomerular diseases. Full article

Complement system inhibitors are emerging as promising therapies in nephrology, particularly for diseases where complement dysregulation is central to pathogenesis. This review summarizes the role of complement activation in kidney diseases and current evidence supporting complement-targeted treatments. As the complement system can be involved in the pathogenesis of different diseases to varying degrees, several research works have been conducted. These research efforts aim, firstly, to understand the mechanisms and role of complement cascade components in the most prevalent nephrological diseases and, secondly, to explore the potential of complement system inhibitors in these conditions and their possible clinical applications. Clinical trials demonstrate that complement inhibitors are most effective in conditions with significant complement involvement, such as C3 glomerulopathy (C3G), atypical hemolytic uremic syndrome (aHUS), and immune complex membranoproliferative glomerulonephritis (IC-MPGN). These agents show variable benefits in diseases with partial complement activation, including lupus nephritis and ANCA-associated vasculitis, while their role in disorders like diabetic nephropathy and focal–segmental glomerulosclerosis remains limited. Complement inhibition offers a targeted strategy to prevent disease progression and improve outcomes in selected nephrological disorders. Full article