Bacterial Toxins Research Articles

Self-stabilization mechanism encoded by a bacterial toxin facilitates reproductive parasitism

A wide variety of maternally transmitted endosymbionts in insects are associated with reproductive parasitism, whereby they interfere with host reproduction to increase the ratio of infected females and spread within populations.1,2 Recent successes in identifying bacterial factors responsible for reproductive parasitism3,4,5,6,7 as well as further omics approaches8,9,10,11,12 have highlighted the common appearance of deubiquitinase domains, although their biological roles-in particular, how they link to distinct manipulative phenotypes-remain poorly defined. Spiroplasma poulsonii is a helical and motile bacterial endosymbiont of Drosophila,13,14 which selectively kills male progeny with a male-killing toxin Spaid (S.poulsonii androcidin), which encodes an ovarian tumor (OTU) deubiquitinase domain.6 Artificial expression of Spaid in flies reproduces male-killing-associated pathologies that include abnormal apoptosis and neural defects during embryogenesis6,15,16,17,18,19; moreover, it highly accumulates on the dosage-compensated male X chromosome,20 congruent with cellular defects such as the DNA damage/chromatin bridge breakage specifically induced upon that chromosome.6,21,22,23 Here, I show that without the function of OTU, Spaid is polyubiquitinated and degraded through the host ubiquitin-proteasome pathway, leading to the attenuation of male-killing activity as shown previously.6 Furthermore, I find that Spaid utilizes its OTU domain to deubiquitinate itself in an intermolecular manner. Collectively, the deubiquitinase domain of Spaid serves as a self-stabilization mechanism to facilitate male killing in flies, optimizing a molecular strategy of endosymbionts that enables the efficient manipulation of the host at a low energetic cost.

In Silico Identification of Cadmium Binding Protein and its Secreted Metalloproteins in Stenotrophomonas maltophilia

Background: Stenotrophomonas maltophilia is a pathogenic bacteria that causes serious infectious complications in humans, especially in immune-compromised patients. Stenotrophomonas maltophilia is a gram-negative bacterium that is multidrug-resistant. Objective: The purpose of the study is to understand the diverse cellular and biological functions of cadmium-binding metalloproteins and to predict their role in pathogenicity, regulation, and growth. Methodology: Different in silico approaches were used to check the Functional Annotation, Subcellular Localization, Gene Ontology, and Bacterial toxin prediction have been used to identify the cellular and biological function of Cd-binding metalloproteins in Stenotrophomonas maltophilia. Results: Identified 116 Cd-binding proteins from the whole proteome sequence and functional domain, family, localization, and toxicity were also studied. Conclusion: The outcomes revealed that this study could be used in understanding the 116 cadmiumbinding proteins from the whole proteome sequence. This study shows the survival, growth, and pathogenicity of the bacteria.

Mast cell-mediated immune regulation in health and disease.

Mast cells are important components of the immune system, and they perform pro-inflammatory as well as anti-inflammatory roles in the complex process of immune regulation in health and disease. Because of their strategic perivascular localization, sensitivity and adaptability to the microenvironment, and ability to release a variety of preformed and newly synthesized effector molecules, mast cells perform unique functions in almost all organs. Additionally, Mast cells express a wide range of surface and cytoplasmic receptors which enable them to respond to a variety of cytokines, chemicals, and pathogens. The mast cell's role as a cellular interface between external and internal environments as well as between vasculature and tissues is critical for protection and repair. Mast cell interactions with different immune and nonimmune cells through secreted inflammatory mediators may also turn in favor of disease promoting agents. First and forefront, mast cells are well recognized for their multifaceted functions in allergic diseases. Reciprocal communication between mast cells and endothelial cells in the presence of bacterial toxins in chronic/sub-clinical infections induce persistent vascular inflammation. We have shown that mast cell proteases and histamine induce endothelial inflammatory responses that are synergistically amplified by bacterial toxins. Mast cells have been shown to exacerbate vascular changes in normal states as well as in chronic or subclinical infections, particularly among cigarette smokers. Furthermore, a potential role of mast cells in SARS-CoV-2-induced dysfunction of the capillary-alveolar interface adds to the growing understanding of mast cells in viral infections. The interaction between mast cells and microglial cells in the brain further highlights their significance in neuroinflammation. This review highlights the significant role of mast cells as the interface that acts as sensor and early responder through interactions with cells in systemic organs and the nervous system.

Translocation of vaginal and cervical low-abundance non-Lactobacillus bacteria notably associate with endometriosis: A pilot study

The etiology remains to be understood for endometriosis (EMS) which affected health negatively for 10% of reproductive-age women globally. Emerging studies found the associations of EMS with genital microbiota dysbiosis. However, the role of vaginal and cervical microbiota is not fully understood for Chinese women. This study recruited forty Chinese women (21 healthy women and 19 EMS patients) to analyze vaginal and cervical microbiota using 16S rRNA amplicon sequencing method. For both sites, there were no significant differences for distribution of microbial samples between control and EMS group, which was concordant with dominated Lactobacillus in both groups. In contrast, we observed accumulation of several low-abundance genera in vaginal and cervical microbiota of EMS patients, such as Fannyhessea, Prevotella, Streptococcus, Bifidobacterium, Veillonella, Megasphaera and Sneathia. Random forest analysis found that translocation of these genera had the significant importance in differentiating EMS patients from controls. In addition, cervix/vagina ratio of these genera also associated with EMS severity. And these genera had notable associations with ascending infection-related functional pathways, including flagellar assembly, bacterial motility proteins, bacterial toxins and epithelial cell signaling in Helicobacter pylori infection. These findings suggest that translocation of specific genera between vaginal and cervical sites play a role in EMS.

Kinetics of Ganglioside-Rich Supported Lipid Bilayer Formation with Tracer Vesicle Fluorescence Imaging.

Gangliosides, forming a class of lipids complemented by sugar chains, influence the lateral distribution of membrane proteins or membrane-binding proteins, act as receptors for viruses and bacterial toxins, and mediate several types of cellular signaling. Gangliosides incorporated into supported lipid bilayers (SLBs) have been widely applied as a model system to examine these biological processes. In this work, we explored how ganglioside composition affects the kinetics of SLB formation using the vesicle rupturing method on a solid surface. We imaged the attachment of vesicles and the subsequent SLB formation using the time-lapse total internal reflection fluorescence microscopy technique. In the early phase, the ganglioside type and concentration influence the adsorption kinetics of vesicles and their residence/lifetime on the surface before rupturing. Our data confirm that a simultaneous rupturing of neighboring surface-adsorbed vesicles forms microscopic lipid patches on the surface and it is triggered by a critical coverage of the vesicles independent of their composition. In the SLB growth phase, lipid patches merge, forming a continuous SLB. The propagation of patch edges catalyzes the process and depends on the ganglioside type. Our pH-dependent experiments confirm that the polar/charged head groups of the gangliosides have a critical role in these steps and phases of SLB formation kinetics.

Abstract P3163: Exosomes From Pseudomonas Aeruginosa Infected Macrophages Drives Cardiomyocyte Contractile Dysfunction

Rationale: Pseudomonas aeruginosa ( P.a. ) infection is very common in ICU patients and is known to increase the mortality rate. Our lab demonstrated that P.a. infection caused severe cardiac dysfunction without disseminating into the heart. However, the mechanism of cardiac complication during P. a. infection is not known; understanding this is critical for the development of host-protective therapy. Thus, we hypothesize that cardiac dysfunction caused by P.a. is either mediated through systemic inflammation and/or the release of exosomes and bacterial outer membrane vesicles from infected cells. Objective: Identify the mechanism of cardiac inflammation and cardiac dysfunction caused by P.a. infection. Methods and Results: To investigate whether P.a. infection causes cardiomyocyte contractile dysfunction, we exposed the hiPSC-CMs with P.a. and monitored the hiPSC-CMs electrical activity using Multi-electrode array (MEA). We found that the contraction of hiPSC-CMs stopped completely at 8h post-infection. Next, to test whether the inflammatory cytokines, exosomes, and bacterial OMVs released upon infection affect contractile function, we exposed the hiPSC-CMs with conditioned media harvested from P.a. infected hMDMs. Our data revealed that exposure of conditioned media to hiSPC-CMs caused severe contractile dysfunction and arrhythmia. Also, we found that conditioned media contains an increased level of inflammatory cytokines IL-1β, TNFα, and IL-6 along with exosomes and OMVs. To test whether heat inactivation of conditioned media preserves the hiPSC-CMs, we inactivated the media and stimulated the cells. Our data suggest that the heat-inactivated conditioned media impaired the hiPSC-CMs contractility, due to the release of exosomal content. Furthermore, based on LC-MS/MS analysis of purified exosomes from P.a. infected hMDMs, we identified that exosomes are packed with bacterial toxins and immunogenic antigens. Conclusion: Our data demonstrate that P.a. releases OMVs and bacterial toxins into the host cells, which are packed in exosomes. Though, infected macrophages release inflammatory cytokines, the main source for hiPSC-CM contractile dysfunction is the release of exosomes packed with bacterial toxins and antigens.

Recent progress in biomarker-based diagnostics of Helicobacter pylori, gastric cancer-causing bacteria.

The progression of any disease and its outcomes depend on the complicated interaction between pathogens, host and environmental factors. Thus, complete knowledge of bacterial toxins involved in pathogenesis isnecessary to develop diagnostic methods and alternative therapies, including vaccines. This review summarizes recently employed biomarkers to diagnose the presence of Helicobacter pylori bacteria. The authors reviewdistinct types of disease-associated biomarkers such as urease, DNA, miRNA, aptamersand bacteriophages that can be utilized as targets to detect Helicobacter pylori and, moreover, gastric cancer in its early stage. A detailed explanation is also given in the context of the recent utilization of these biomarkers in the development of a highly specific and sensitive biosensing platform.

High-Throughput Analysis of Bacterial Toxic Lipopolysaccharide in Water by Dual-Wavelength Monitoring Using a Ratiometric Fluorescent Chemosensor.

Lipopolysaccharide (LPS) is a bacterial toxin that causes fever in humans. Our small-molecule chemosensor named Zn-dpa-C2OPy shows rapid ratiometric fluorescence response to LPS in water with a detection limit of 11 pM, which is lower than that of our previously reported sensor. Spectroscopic measurements (fluorescence, absorbance, 1H NMR, and fluorescence lifetime), dynamic light scattering measurements, and transmission electron microscopy observations revealed that the fluorescence response was induced by the changes in the aggregation state via multi-point recognition of LPS through hydrophobic and electrostatic interactions, in addition to the coordination between the zinc(II)-dipicolylamine moiety of the chemosensor and the phosphate group of LPS. The proposed Zn-dpa-C2OPy chemosensor was applied to an original flow injection analysis (FIA) system with a self-developed dual-wavelength fluorophotometer, and a high throughput of 36 samples per hour was achieved. These results demonstrate the feasibility of this unique methodology combining a ratiometric fluorescent chemosensor and FIA for continuous online monitoring of LPS in water.

Protein biomarker for early diagnosis of microbial toxin contamination: Using Aspergillus flavus as an example

AbstractMicrobial toxins are important factors that contribute to human diseases and food losses. Predicting the production of these toxins before they occur is a significant challenge. In this study, we innovatively developed a strategy called targeted acquisition of toxin‐related immunogen (TATRI) to identify early diagnostic biomarkers for microbial toxins. Taking Aspergillus flavus as an example, we employed an immunoassay‐based screening approach to identify nanobodies that exhibited significant response signals to different toxigenic strains. Subsequently, we isolated and purified the specific immunogen pre‐aflatoxin biomarker PAB‐01 that bound to the selected nanobody. The results showed that the level of PAB‐01 was positively correlated with the toxin‐producing ability of A. flavus strains and could be detected before the production of aflatoxins. It met the essential requirements as an early diagnostic biomarker for aflatoxin contamination. Protein identification and bioinformatics analysis revealed that PAB‐01 is a glycoprotein that can be secreted into the extracellular space. It is located on chromosome 5 of A. flavus and belongs to the 75 family of glycoside hydrolases. Furthermore, we used 7 g/kg as the critical concentration of PAB‐01 to diagnose the risk of aflatoxin contamination in stored peanuts, with an accuracy rate of 75.9% for high‐risk samples. In summary, this work provides a promising approach for the identification of protein biomarkers prior to microbial toxin production and the establishment of early diagnostic techniques for microbial toxins.

Fast drosophila enterocyte regrowth after infection involves a reverse metabolic flux driven by an amino acid transporter

Upon exposure to a bacterial pore-forming toxin, enterocytes rapidly purge their apical cytoplasm into the gut lumen, resulting in a thin intestinal epithelium. The enterocytes regain their original shape and thickness within 16h after the ingestion of the bacteria. Here, we show that the regrowth of Drosophila enterocytes entails an inversion of metabolic fluxes from the organism back toward the intestine. We identify a proton-assisted transporter, Arcus, that is required for the reverse absorption of amino acids and the timely recovery of the intestinal epithelium. Arcus is required for a peak of amino acids appearing in the hemolymph shortly after infection. The regrowth of enterocytes involves the insulin signaling pathway and Myc. The purge decreases Myc mRNA levels, which subsequently remain at low levels in the arcus mutant. Interestingly, the action of arcus and Myc in the intestinal epithelium is not cell-autonomous, suggesting amino acid fluxes within the intestinal epithelium.

The Effects of Doxapram Blocking the Response of Gram-Negative Bacterial Toxin (LPS) at Glutamatergic Synapses.

Lipopolysaccharides (LPS) associated with Gram-negative bacteria are one factor responsible for triggering the mammalian immune response. Blocking the action of LPS is key to reducing its downstream effects. However, the direct action of LPS on cells is not yet fully addressed. LPS can have rapid, direct effects on cells in the absence of a systemic immune response. Recent studies have shown that doxapram, a blocker of a subset of K2P channels, also blocks the acute actions of LPS. Doxapram was evaluated to determine if such action also occurs at glutamatergic synapses in which it is known that LPS can increase synaptic transmission. Doxapram at 5 mM first enhanced synaptic transmission, then reduced synaptic response, while 10 mM rapidly blocked transmission. Doxapram at 5 mM blocked the excitatory response induced by LPS. Enhancing synaptic transmission with LPS and then applying LPS combined with doxapram also resulted in retarding the response of LPS. It is possible doxapram and LPS are mediated via a similar receptor or cellular responses. The potential of designing pharmacological compounds with a similar structure to doxapram and determining the binding of such compounds can aid in addressing the acute, direct actions by LPS on cells.

Bacterial secretion systems contribute to rapid tissue decay in button mushroom soft rot disease.

The soft rot pathogen Janthinobacterium agaricidamnosum causes devastating damage to button mushrooms (Agaricus bisporus), one of the most cultivated and commercially relevant mushrooms. We previously discovered that this pathogen releases the membrane-disrupting lipopeptide jagaricin. This bacterial toxin, however, could not solely explain the rapid decay of mushroom fruiting bodies, indicating that J. agaricidamnosum implements a more sophisticated infection strategy. In this study, we show that secretion systems play a crucial role in soft rot disease. By mining the genome of J. agaricidamnosum, we identified gene clusters encoding a type I (T1SS), a type II (T2SS), a type III (T3SS), and two type VI secretion systems (T6SSs). We targeted the T2SS and T3SS for gene inactivation studies, and subsequent bioassays implicated both in soft rot disease. Furthermore, through a combination of comparative secretome analysis and activity-guided fractionation, we identified a number of secreted lytic enzymes responsible for mushroom damage. Our findings regarding the contribution of secretion systems to the disease process expand the current knowledge of bacterial soft rot pathogens and represent a significant stride toward identifying targets for their disarmament with secretion system inhibitors. IMPORTANCE The button mushroom (Agaricus bisporus) is the most popular edible mushroom in the Western world. However, mushroom crops can fall victim to serious bacterial diseases that are a major threat to the mushroom industry, among them being soft rot disease caused by Janthinobacterium agaricidamnosum. Here, we show that the rapid dissolution of mushroom fruiting bodies after bacterial invasion is due to degradative enzymes and putative effector proteins secreted via the type II secretion system (T2SS) and the type III secretion system (T3SS), respectively. The ability to degrade mushroom tissue is significantly attenuated in secretion-deficient mutants, which establishes that secretion systems are key factors in mushroom soft rot disease. This insight is of both ecological and agricultural relevance by shedding light on the disease processes behind a pathogenic bacterial-fungal interaction which, in turn, serves as a starting point for the development of secretion system inhibitors to control disease progression.

Bacterial toxins and heart function: heat-labile Escherichia coli enterotoxin B promotes changes in cardiac function with possible relevance for sudden cardiac death.

The online version contains supplementary material available at 10.1007/s12551-023-01100-6.

Animal Toxins: A Historical Outlook at the Institut Pasteur of Paris

Humans have faced poisonous animals since the most ancient times. It is recognized that certain animals, like specific plants, produce toxic substances that can be lethal, but that can also have therapeutic or psychoactive effects. The use of the term “venom”, which initially designated a poison, remedy, or magic drug, is now confined to animal poisons delivered by biting. Following Louis Pasteur’s work on pathogenic microorganisms, it was hypothesized that venoms could be related to bacterial toxins and that the process of pathogenicity attenuation could be applied to venoms for the prevention and treatment of envenomation. Cesaire Phisalix and Gabriel Bertrand from the National Museum of Natural History as well as Albert Calmette from the Institut Pasteur in Paris were pioneers in the development of antivenomous serotherapy. Gaston Ramon refined the process of venom attenuation for the immunization of horses using a formalin treatment method that was successful for diphtheria and tetanus toxins. This paved the way for the production of antivenomous sera at the Institut Pasteur, as well as for research on venom constituents and the characterization of their biological activities. The specific activities of certain venom components, such as those involved in blood coagulation or the regulation of chloride ion channels, raises the possibility of developing novel therapeutic drugs that could serve as anticoagulants or as a treatment for cystic fibrosis, for example. Scientists of the Institut Pasteur of Paris have significantly contributed to the study of snake venoms, a topic that is reported in this review.

Mini-review: microbiota have potential to prevent PEDV infection by improved intestinal barrier.

Porcine epidemic diarrhea virus (PEDV) infection poses a significant threat to the global pig industry. Current prevention and control strategies are inadequate in protecting pigs from new PEDV variants. This review aims to examine the relationship between PEDV and intestinal microbes, and investigate whether modulating intestinal microbes could affect PEDV infection. The mechanisms by which various intestinal microbes affect viral infection were initially introduced. Intestinal microbes can influence enteric viral infection through direct contact, such as binding, or by affecting interferons (IFNs) production and the intestinal barrier. Influencing the intestinal barrier by microbes can impact PEDV infection in young piglets. To narrow down the range of microbes that may influence PEDV infection, this review summarized microbes that change after infection. Short chain fatty acids (SCFAs), bacterial cell components, and toxins from microbes were identified as important mediators affecting PEDV infection. SCFAs primarily strengthen the intestinal barrier and inhibit intestinal inflammation, while bacterial cell components and toxins are more likely to damage the intestinal barrier. Therefore, this review hypothesizes that fecal transplantation, which allows the host to colonize more SCFAs-producing microbes, may prevent PEDV infection. However, these hypotheses require further proof, and the transplantation of intestinal microbes in pigs requires more exploration.

TLR4, MyD88, and TNF-α Expression in the Lungs of Akkaraman and Romanov Lambs in Response to LPS and LTA.

Toll-like receptors are involved in the recognition of bacterial toxins, which cause infection in the respiratory system. This study aimed to evaluate microanatomical and histological alterations in the lungs of 24 healthy Akkaraman and Romanov lambs after the administration of lipoteichoic acid (LTA), lipopolysaccharide (LPS), and LTA + LPS and investigate the gene, protein, and immune expression levels of TLR4, MyD88, and TNF-α molecules, known to have immune functions. Microanatomical examinations showed thickened peribronchial and alveolar walls in the lungs of groups LTA, LPS, and LTA + LPS of both breeds due to immune cell infiltration. TLR4, MyD88, and TNF-α immunoexpressions were positive to varying degrees in the cytoplasm and nucleus of the bronchial and bronchiolar luminal epithelial cells, alveolar epithelial cells, and alveolar macrophages. TLR4 and TNF-α protein expressions were statistically different in the LPS-treated Romanov lambs, compared to the other groups. Among the Akkaraman lambs, TLR4 gene expression was significantly higher in group LPS, and among the Romanov lambs, TLR4, MyD88, and TNF-α gene expressions were significantly higher in group LTA + LPS. Therefore, TLR4, MyD88, and TNF-α molecules, involved in the immune response, were found to be expressed at different levels against LTA and LPS in the lungs of two different sheep breeds.

Cancer Drug Delivery Systems Using Bacterial Toxin Translocation Mechanisms.

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. Bacterial toxins have evolved naturally to specifically target cell subtypes via their receptor binding module, penetrating the cell membrane efficiently through the membrane translocation process and then successfully delivering the toxic cargo into the host cytosol. They have, thus, been harnessed for the delivery of various drugs. In this review, we focus on bacterial toxin translocation mechanisms and recent progress in the targeted delivery systems of cancer therapy drugs that have been inspired by the receptor binding and membrane translocation processes of the anthrax toxin protective antigen, diphtheria toxin, and Pseudomonas exotoxin A. We also discuss the challenges and limitations of these studies that should be addressed before bacterial toxin-based drug delivery systems can become a viable new generation of drug delivery approaches in clinical translation.

AB Toxins as High-Affinity Ligands for Cell Targeting in Cancer Therapy.

Conventional targeted therapies for the treatment of cancer have limitations, including the development of acquired resistance. However, novel alternatives have emerged in the form of targeted therapies based on AB toxins. These biotoxins are a diverse group of highly poisonous molecules that show a nanomolar affinity for their target cell receptors, making them an invaluable source of ligands for biomedical applications. Bacterial AB toxins, in particular, are modular proteins that can be genetically engineered to develop high-affinity therapeutic compounds. These toxins consist of two distinct domains: a catalytically active domain and an innocuous domain that acts as a ligand, directing the catalytic domain to the target cells. Interestingly, many tumor cells show receptors on the surface that are recognized by AB toxins, making these high-affinity proteins promising tools for developing new methods for targeting anticancer therapies. Here we describe the structure and mechanisms of action of Diphtheria (Dtx), Anthrax (Atx), Shiga (Stx), and Cholera (Ctx) toxins, and review the potential uses of AB toxins in cancer therapy. We also discuss the main advances in this field, some successful results, and, finally, the possible development of innovative and precise applications in oncology based on engineered recombinant AB toxins.

Modulation of innate lymphoid cells by enteric bacterial pathogens.

Innate lymphoid cells (ILCs) are key regulators of tissue homeostasis, inflammation, and immunity to infections. ILCs rapidly respond to environmental cues such as cytokines, microbiota and invading pathogens which regulate their function and phenotype. Even though ILCs are rare cells, they are enriched at barrier surfaces such as the gastrointestinal (GI) tract, and they are often critical to the host's immune response to eliminate pathogens. On the other side of host-pathogen interactions, pathogenic bacteria also have the means to modulate these immune responses. Manipulation or evasion of the immune cells is often to the pathogen's benefit and/or to the detriment of competing microbiota. In some instances, specific bacterial virulence factors or toxins have been implicated in how the pathogen modulates immunity. In this review, we discuss the recent progress made towards understanding the role of non-cytotoxic ILCs during enteric bacterial infections, how these pathogens can modulate the immune response, and the implications these have on developing new therapies to combat infection.

Specific Clearance of Lipopolysaccharide from Blood Based on Peptide Bottlebrush Polymer for Sepsis Therapy.

Lipopolysaccharide (LPS) is the primary bacterial toxin that is vital to the pathogenesis and progression of sepsis associated with extremely high morbidity and mortality worldwide. However, specific clearance of LPS from circulating blood is highly challenging because of the structural complexity and its variation between/within bacterial species. Herein, a robust strategy based on phage display screening and hemocompatible peptide bottlebrush polymer design for specific clearance of targeted LPS from circulating blood is proposed. Using LPS extracted from Escherichia coli as an example, a novel peptide (HWKAVNWLKPWT) with high affinity (KD < 1.0 nм), specificity, and neutralization activity (95.9 ± 0.1%) against the targeted LPS is discovered via iterative affinity selection coupled with endotoxin detoxificationscreening. A hemocompatible bottlebrush polymer bearing the short peptide [poly(PEGMEA-co-PEP-1)] exhibits high LPS selectivity to reduce circulating LPS level from 2.63 ± 0.01 to 0.78 ± 0.05 EU mL-1 in sepsis rabbits via extracorporeal hemoperfusion (LPS clearance ratio > 70%), reversing the LPS-induced leukocytopenia and multiple organ damages significantly. This work provides a universal paradigm for developing a highly selective hemoadsorbent library fully covering the LPS family, which is promising to create a new era of precision medicine in sepsis therapy.