Treatment Of Infectious Diseases Research Articles

Mavintramycin A is a promising antibiotic for treating Mycobacterium avium complex infectious disease.

Mycobacterium avium complex (MAC) is a serious disease that is mainly caused by infection with the non-tuberculous mycobacteria (NTM), Mycobacterium avium and Mycobacterium intracellulare. Seven new compounds, designated mavintramycins A-G (1-7), were isolated along with structurally related compounds, including amicetin (9) and plicacetin (10), from the culture broth of Streptomyces sp. OPMA40551 as anti-MAC compounds that were active against M. avium and M. intracellulare. Among them, mavintramycin A showed the most potent and selective inhibition of M. avium and M. intracellulare. Furthermore, mavintramycin A was active against more than 40 clinically isolated M. avium, including multidrug-resistant strains, and inhibited the growth of M. avium in a persistent infection cell model using THP-1 macrophages. Mavintramycin A also exhibited in vivo efficacy in silkworm and mouse infection assays with NTM. An experiment to elucidate its mechanism of action revealed that mavintramycin A inhibits protein synthesis by binding to 23S ribosomal RNA in NTM. Mavintramycin A, with a different chemical structure from those of clinically used agents, is a promising drug candidate for the treatment of MAC infectious disease.

CGAS-STING pathway agonists are promising vaccine adjuvants.

Adjuvants are of critical value in vaccine development as they act on enhancing immunogenicity of antigen and inducing long-lasting immunity. However, there are only a few adjuvants that have been approved for clinical use, which highlights the need for exploring and developing new adjuvants to meet the growing demand for vaccination. Recently, emerging evidence demonstrates that the cGAS-STING pathway orchestrates innate and adaptive immunity by generating type I interferon responses. Many cGAS-STING pathway agonists have been developed and tested in preclinical research for the treatment of cancer or infectious diseases with promising results. As adjuvants, cGAS-STING agonists have demonstrated their potential to activate robust defense immunity in various diseases, including COVID-19 infection. This review summarized the current developments in the field of cGAS-STING agonists with a special focus on the latest applications of cGAS-STING agonists as adjuvants in vaccination. Potential challenges were also discussed in the hope of sparking future research interests to further the development of cGAS-STING as vaccine adjuvants.

Some species of the genus Fagopyrum: chemical composition, pharmacological effects, prospects of use

This review analyzes and summarizes the information of research by domestic and foreign scientists on the chemical composition, pharmacological activity of metabolites of plants of the genus Fagopyrum. The genus Fagopyrum, a member of the Polygonaceae family, includes 15 species, most of them are cultivated on an industrial scale on the territory of the Russian Federation, China, India, Indonesia and North American countries. The greatest interest in medicine and pharmacy is represented by four types of buckwheat: seed buckwheat (Fagopyrum esculentum) and Tatar buckwheat (Fagopyrum tataricum), perennial buckwheat (Fagopyrum dibotrys) and red-stem buckwheat (Fagopyrum rubricaulis). These types are widely used in traditional medicine of China, Tibet, the Russian Federation, for the treatment of lung diseases, skin, edematous syndromes and infectious diseases. Currently, more than 150 compounds related to flavonoids, phenylpropanoids, tannins, phagopyritols, triterpenoids, steroids, fatty acids, essential oils, alkaloids, anthraquinones, coumarins, vitamins, amino acids, macro- and microelements have been isolated and identified from the studied buckwheat species. Extracts and isolated individual compounds have a wide range of pharmacological effects: antitumor, antioxidant, anti-inflammatory, hepatoprotective, hypoglycemic, antiallergic, antibacterial, angioprotective and adaptogenic. The information given in the review indicates that plants of the genus Fagopyrum are promising for further study and use in various industries.

Development of a Platform for Natural Killer Cell Therapy with Antiviral Efficacy

Various vaccines were rapidly developed during the COVID-19 pandemic to prevent and treat infections but global infections continue, and concerns about new mutations and infectious diseases persist. Thus, active research focuses on developing, producing, and supplying vaccines and treatments for various infectious diseases and potential pandemics.Natural killer(NK) cells, as innate immune cells, can recognize and eliminate abnormal cells like virus-infected and cancer cells. Hence, their development as anticancer and antiviral treatments is rapidly advancing. In this study, optimal short-term culture conditions were identified for allogeneic NK cells by simplifying the culture process through the isolation of NK cells(referred to as NKi cells) and eliminating CD3+ cells(referred to as CD3-cells). NK cells demonstrated reduced viral titer in injection of NK cells into SARS-CoV-2 infected ACE-tg mice increased survival.The study's findings could form the basis for an antiviral treatment platform that swiftly responds to new viral disease pandemics.

Emerging Nanobiotechnology Solutions for Infectious Disease Diagnosis and Treatment

Emerging Nanobiotechnology Solutions for Infectious Disease Diagnosis and Treatment

Genetic characterization of multidrug-resistant Escherichia coli harboring colistin-resistant gene isolated from food animals in food supply chain.

Colistin is widely used for the prophylaxis and treatment of infectious disease in humans and livestock. However, the global food chain may actively promote the dissemination of colistin-resistant bacteria in the world. Mobile colistin-resistant (mcr) genes have spread globally, in both communities and hospitals. This study sought to genomically characterize mcr-mediated colistin resistance in 16 Escherichia coli strains isolated from retail meat samples using whole genome sequencing with short-read and long-read platforms. To assess colistin resistance and the transferability of mcr genes, antimicrobial susceptibility testing and conjugation experiments were conducted. Among the 16 isolates, 11 contained mcr-1, whereas three carried mcr-3 and two contained mcr-1 and mcr-3. All isolates had minimum inhibitory concentration (MIC) for colistin in the range 1-64 μg/mL. Notably, 15 out of the 16 isolates demonstrated successful transfer of mcr genes via conjugation, indicative of their presence on plasmids. In contrast, the KK3 strain did not exhibit such transferability. Replicon types of mcr-1-containing plasmids included IncI2 and IncX4, while IncFIB, IncFII, and IncP1 contained mcr-3. Another single strain carried mcr-1.1 on IncX4 and mcr-3.5 on IncP1. Notably, one isolate contained mcr-1.1 located on a chromosome and carrying mcr-3.1 on the IncFIB plasmid. The chromosomal location of the mcr gene may ensure a steady spread of resistance in the absence of selective pressure. Retail meat products may act as critical reservoirs of plasmid-mediated colistin resistance that has been transmitted to humans.

In Vitro Antibacterial Activity of Microbial Natural Products against Bacterial Pathogens of Veterinary and Zoonotic Relevance.

Antimicrobial resistance (AMR) is considered one of the greatest threats to both human and animal health. Efforts to address AMR include implementing antimicrobial stewardship programs and introducing alternative treatment options. Nevertheless, effective treatment of infectious diseases caused by bacteria will still require the identification and development of new antimicrobial agents. Eight different natural products were tested for antimicrobial activity against seven pathogenic bacterial species (Brachyspira sp., Chlamydia sp., Clostridioides sp., Mannheimia sp., Mycobacterium sp., Mycoplasma sp., Pasteurella sp.). In a first pre-screening, most compounds (five out of eight) inhibited bacterial growth only at high concentrations, but three natural products (celastramycin A [CA], closthioamide [CT], maduranic acid [MA]) displayed activity at concentrations <2 µg/mL against Pasteurella sp. and two of them (CA and CT) also against Mannheimia sp. Those results were confirmed by testing a larger collection of isolates encompassing 64 Pasteurella and 56 Mannheimia field isolates originating from pigs or cattle, which yielded MIC90 values of 0.5, 0.5, and 2 µg/mL against Pasteurella and 0.5, 4, and >16 µg/mL against Mannheimia for CA, CT, and MA, respectively. CA, CT, and MA exhibited higher MIC50 and MIC90 values against Pasteurella isolates with a known AMR phenotype against commonly used therapeutic antimicrobial agents than against isolates with unknown AMR profiles. This study demonstrates the importance of whole-cell antibacterial screening of natural products to identify promising scaffolds with broad- or narrow-spectrum antimicrobial activity against important Gram-negative veterinary pathogens with zoonotic potential.

Nanopore sequencing of infectious fluid is a promising supplement for gold-standard culture in real-world clinical scenario.

Infectious diseases are major causes of morbidity and mortality worldwide, necessitating the rapid identification and accurate diagnosis of pathogens. While unbiased metagenomic next-generation sequencing (mNGS) has been extensively utilized in clinical pathogen identification and scientific microbiome detection, there is limited research about the application of nanopore platform-based mNGS in the diagnostic performance of various infectious fluid samples. In this study, we collected 297 suspected infectious fluids from 10 clinical centers and detected them with conventional microbiology culture and nanopore platform-based mNGS. The objective was to assess detective and diagnostic performance of nanopore-sequencing technology (NST) in real-world scenarios. Combined with gold-standard culture and clinical adjudication, nanopore sequencing demonstrated nearly 100% positive predictive agreements in microbial-colonized sites, such as the respiratory and urinary tracts. For samples collected from initially sterile body sites, the detected microorganisms were highly suspected pathogens, and the negative predictive agreements were relatively higher than those in the microbial-colonized sites, particularly with 100% in abscess and 95.7% in cerebrospinal fluid. Furthermore, consistent performance was also observed in the identification of antimicrobial resistance genes and drug susceptibility testing of pathogenic strains of Escherichia coli, Staphylococcus aureus, and Acinetobacter baumannii. Rapid NST is a promising clinical tool to supplement gold-standard culture, and it has the potential improve patient prognosis and facilitate clinical treatment of infectious diseases.

Prespecified Homeopathic Medicines in the Prevention of Confirmed and Suspected Cases of COVID-19: A Community-Based, Double-Blind, Randomized, Placebo-Controlled Prophylaxis Trial

Introduction: Homeopathic medicines have been used for decades in the prevention and treatment of infectious diseases. However, the preventive efficacy of specific homeopathic medicines in COVID-19 is not well characterized. This study aimed to evaluate the comparative efficacy of prespecified homeopathic medicines in preventing COVID-19. Methods: A community-based, double-blind, randomized, placebo-controlled trial was conducted on 4,034 participants residing in Ward No. 27 of the Howrah Municipal Corporation in India. Participants were randomized to receive one of three prespecified homeopathic medicines [Influenzinum 30C, Arsenicum album 30C, Anas barbariae hepatis et cordis extractum 200K (Oscillococcinum®)], or placebo. The outcomes were the incidence of laboratory-confirmed and suspected cases of COVID-19 during a follow-up period of 1 month. Results: During the follow-up period, a total of 13 new laboratory-confirmed COVID-19 cases were reported in the study population. Among these, 5 cases in Influenzinum group, 2 cases in Arsenicum album group, 1 case in Oscillococcinum® group, and 5 cases in Placebo group were reported. On the other hand, number of suspected COVID-19 cases was significantly less in all the three homeopathic medicine groups compared to placebo. The least number of suspected cases reported in the Oscillococcinum® group (aOR: 0.058; 95% confidence interval [CI]: 0.029, 0.114), followed by the Arsenicum album (aOR: 0.337; 95% CI: 0.238, 0.475) and Influenzinum (aOR: 0.539; 95% CI: 0.401, 0.726) groups. Conclusion: Prespecified homeopathic medicines, particularly Oscillococcinum® and Arsenicum album 30C, may have a role in preventing COVID-19, especially in reducing the incidence of suspected or COVID-19-like respiratory illnesses. However, the result failed to demonstrate a statistically significant difference in the occurrence of confirmed cases of COVID-19 between the study groups. Further research is needed to evaluate the efficacy of these medicines in different populations and settings.

The Effect of Cholesterol Content on the Adjuvant Activity of Nucleic-Acid-Free Lipid Nanoparticles.

RNA vaccines are applicable to the treatment of various infectious diseases via the inducement of robust immune responses against target antigens by expressing antigen proteins in the human body. The delivery of messenger RNA by lipid nanoparticles (LNPs) has become a versatile drug delivery system used in the administration of RNA vaccines. LNPs are widely considered to possess adjuvant activity that induces a strong immune response. However, the properties of LNPs that contribute to their adjuvant activity continue to require clarification. To characterize the relationships between the lipid composition, particle morphology, and adjuvant activity of LNPs, the nanostructures of LNPs and their antibody production were evaluated. To simply compare the adjuvant activity of LNPs, empty LNPs were subcutaneously injected with recombinant proteins. Consistent with previous research, the presence of ionizable lipids was one of the determinant factors. Adjuvant activity was induced when a tiny cholesterol assembly (cholesterol-induced phase, ChiP) was formed according to the amount of cholesterol present. Moreover, adjuvant activity was diminished when the content of cholesterol was excessive. Thus, it is plausible that an intermediate structure of cholesterol (not in a crystalline-like state) in an intra-particle space could be closely related to the immunogenicity of LNPs.

Conjugation of tetracycline with carrier proteins and production of its polyclonal antibody for the development of rapid test

Tetracycline (TC) is a broad-spectrum antibiotic used in the treatment of several infectious diseases. The excessive use of tetracycline antibiotics, especially tetracyclines in livestock, has raised concerns about residues of tetracycline antibiotics in food that may affect consumers' health. It is necessary to develop a rapid test strip for detecting tetracycline antibiotic residues in food and animal feed. This paper presents the suitable conditions for the conjugation of tetracycline to BSA or KLH: molar ratio of TC:BSA/KLH was 25:1, formaldehyde concentration of 5 %, temperature of 4oC and reaction time of 4 hours. The KLH-TC conjugate was used to successfully raise polyclonal antibodies against TC in rabbits. The anti-TC polyclonal antibodies were purified and could be used for the development of the lateral flow immunoassay test strip for the detection of tetracycline.

Nanotechnology in the Diagnosis and Treatment of Antibiotic-Resistant Infections.

The development of antimicrobial resistance (AMR), along with the relative reduction in the production of new antimicrobials, significantly limits the therapeutic options in infectious diseases. Thus, novel treatments, especially in the current era, where AMR is increasing, are urgently needed. There are several ongoing studies on non-classical therapies for infectious diseases, such as bacteriophages, antimicrobial peptides, and nanotechnology, among others. Nanomaterials involve materials on the nanoscale that could be used in the diagnosis, treatment, and prevention of infectious diseases. This review provides an overview of the applications of nanotechnology in the diagnosis and treatment of infectious diseases from a clinician's perspective, with a focus on pathogens with AMR. Applications of nanomaterials in diagnosis, by taking advantage of their electrochemical, optic, magnetic, and fluorescent properties, are described. Moreover, the potential of metallic or organic nanoparticles (NPs) in the treatment of infections is also addressed. Finally, the potential use of NPs in the development of safe and efficient vaccines is also reviewed. Further studies are needed to prove the safety and efficacy of NPs that would facilitate their approval by regulatory authorities for clinical use.

The use of nanoparticles in the treatment of infectious diseases and cancer, dental applications and tissue regeneration: a review.

The emergence of nanotechnology as a field of study can be traced back to the 1980s, at which point the means to artificially produce, control, and observe matter on a nanometer level was made viable. Recent advancements in technology have enabled us to extend our reach to the nanoscale, which has presented an unparalleled opportunity to directly target biomolecular interactions. As a result of these developments, there is a drive to arise intelligent nanostructures capable of overcoming the obstacles that have impeded the progress of conventional pharmacological methodologies. After four decades, the gradual amalgamation of bio- and nanotechnologies is initiating a revolution in the realm of disease detection, treatment, and monitoring, as well as unsolved medical predicaments. Although a significant portion of research in the field is still confined to laboratories, the initial application of nanotechnology as treatments, vaccines, pharmaceuticals, and diagnostic equipment has now obtained endorsement for commercialization and clinical practice. The current issue presents an overview of the latest progress in nanomedical strategies towards alleviating antibiotic resistance, diagnosing and treating cancer, addressing neurodegenerative disorders, and an array of applications, encompassing dentistry and tuberculosis treatment. The current investigation also scrutinizes the deployment of sophisticated smart nanostructured materials in fields of application such as regenerative medicine, as well as the management of targeted and sustained release of pharmaceuticals and therapeutic interventions. The aforementioned concept exhibits the potential for revolutionary advancements within the field of immunotherapy, as it introduces the utilization of implanted vaccine technology to consistently regulate and augment immune functions. Concurrently with the endeavor to attain the advantages of nanomedical intervention, it is essential to enhance the unceasing emphasis on nanotoxicological research and the regulation of nanomedications' safety. This initiative is crucial in achieving the advancement in medicine that currently lies within our reach.

Nanoparticle-Based Immunotherapy for Reversing T-Cell Exhaustion.

T-cell exhaustion refers to a state of T-cell dysfunction commonly observed in chronic infections and cancer. Immune checkpoint molecules blockading using PD-1 and TIM-3 antibodies have shown promising results in reversing exhaustion, but this approach has several limitations. The treatment of T-cell exhaustion is still facing great challenges, making it imperative to explore new therapeutic strategies. With the development of nanotechnology, nanoparticles have successfully been applied as drug carriers and delivery systems in the treatment of cancer and infectious diseases. Furthermore, nanoparticle-based immunotherapy has emerged as a crucial approach to reverse exhaustion. Here, we have compiled the latest advances in T-cell exhaustion, with a particular focus on the characteristics of exhaustion that can be targeted. Additionally, the emerging nanoparticle-based delivery systems were also reviewed. Moreover, we have discussed, in detail, nanoparticle-based immunotherapies that aim to reverse exhaustion, including targeting immune checkpoint blockades, remodeling the tumor microenvironment, and targeting the metabolism of exhausted T cells, etc. These data could aid in comprehending the immunopathogenesis of exhaustion and accomplishing the objective of preventing and treating chronic diseases or cancer.

Mannose Ligands for Mannose Receptor Targeting.

The mannose receptor (MR, CD 206) is an endocytic receptor primarily expressed by macrophages and dendritic cells, which plays a critical role in both endocytosis and antigen processing and presentation. MR carbohydrate recognition domains (CRDs) exhibit a high binding affinity for branched and linear oligosaccharides. Furthermore, multivalent mannose presentation on the various templates like peptides, proteins, polymers, micelles, and dendrimers was proven to be a valuable approach for the selective and efficient delivery of various therapeutically active agents to MR. This review provides a detailed account of the most relevant and recent aspects of the synthesis and application of mannosylated bioactive formulations for MR-mediated delivery in treatments of cancer and other infectious diseases. It further highlights recent findings related to the necessary structural features of the mannose-containing ligands for successful binding to the MR.

[Investigation of the Antibacterial Effect of Taraxacum officinale Extracts Extracted in Different Solvents on Bacteroides fragilis ATCC 25285 Standard Strain by Broth Microdilution Method].

Bacteria causing hospital-associated infections continue to become resistant due to antibiotic resistance, which has become a global problem worldwide and accordingly, the antibiotic options used in the treatment of infectious diseases caused by these bacteria are limited. In the light of the data obtained from experimental studies on plants, it is thought that plant extracts may be a promising option in the treatment of infectious diseases. In this study, it was aimed to determine the antibacterial activity of Taraxacum officinale extracts on Bacteroides fragilis ATCC 25285 standard strain by broth microdilution method and to pioneer different studies that will investigate the antibacterial effects of plant extracts on resistant B.fragilis strains that cause hospital-acquired opportunistic infections after invasive interventions and trauma. In this study, the T.officinale plant collected as a result of field work was divided into root, leaf and flower parts and dried at 70 °C for 24 hours and then turned into powder. Dried plant samples were extracted in ethanol and methanol for 24 hours. The obtained extracts were stored at -80 °C to be used in the broth microdilution method. B.fragilis ATCC 25285 standard strain was used as the bacterial strain. As a result of the experiments performed with broth microdilution method, the MIC (minimum inhibitory concentration) value of root, leaf and flower extracts with ethanol was determined as 200 μg/ mL, the methanolic root extract as 100 μg/mL and the methanolic leaf and flower extracts as 200 μg/mL. As a result, ethanol and methanol plant extracts were found to be effective on B.fragilis strain.

New thiazolyl-isoxazole derivatives as potential anti-infective agents: design, synthesis, in vitro and in silico antimicrobial efficacy

Antimicrobial resistance threatens the efficacious prevention and treatment of infectious diseases caused by microorganisms. To combat microbial infections, the need for new drug candidates is essential. In this context, the design, synthesis, antimicrobial screening, and in silico study of a new series of 5-aryl-3-(2-arylthiazol-4-yl)isoxazole (9a-t) have been reported. The structure of new compounds was confirmed by spectrometric methods. Compounds 9a-t were evaluated for in vitro antitubercular and antimicrobial activity. Against M. tuberculosis H37Rv, fourteen compounds showed good to excellent antitubercular activity with MIC 2.01–9.80 µM. Compounds 9a, 9b, and 9r showed four-fold more activity than the reference drug isoniazid. Nine compounds, 9a, 9b, 9d, 9e, 9i, 9q, 9r, 9s, and 9t, showed good antibacterial activity against E. coli with MIC 7.8–15.62 µg/mL. Against A. niger, four compounds showed good activity with MIC 31.25 µg/mL. Against C. albicans, all twenty compounds reported excellent to good activity with MIC 7.8–31.25 µg/mL. Compounds 9c–e, 9g–j, and 9q–t showed comparable activity concerning the reference drug fluconazole. The compounds 9a-t were screened for cytotoxicity against 3t3l1 cell lines and found to be less or non-cytotoxic. The in silico study exposed that these compounds displayed high affinity towards the M. tuberculosis targets PanK, DprE1, DHFR, PknA, KasA, and Pks13, and C. albicans targets NMT, CYP51, and CS. The compound 9r was evaluated for structural dynamics and molecular dynamics simulations. The potent antitubercular and antimicrobial activity of 5-aryl-3-(2-arylthiazol-4-yl)isoxazole (9a–t) derivatives has recommended that these compounds could assist in treating microbial infections. Communicated by Ramaswamy H. Sarma

Phytochemical Analysis and Antimicrobial Activity of Pongamia Pinnata: A Comprehensive Study

Background: Antimicrobial resistance (AMR) poses a significant global health challenge, exacerbated by the misuse of antimicrobial agents. With the rising prevalence of AMR in various plant and animal pathogens, there is an urgent need to explore alternative therapeutic options. Plant extracts, historically utilized for disease treatment, offer a promising avenue. Pongamia pinnata, also known as Indian Karanja, is notable for its rich phytochemical content and has been the subject of recent scientific interest. Objective: The primary aim of this study is to investigate the antimicrobial efficacy of P. pinnata extracts, prepared using the Ultrasonic Assisted Extraction (UAE) method, against a range of bacterial and fungal species known to exhibit AMR. Methods: In this study, an experimental laboratory design was utilized to evaluate the antimicrobial properties of Pongamia pinnata. Aqueous and alcoholic extracts of P. pinnata were prepared and subjected to biochemical analysis to identify the spectrum of phytochemicals present. The antimicrobial activity of these extracts was then assessed using the well-diffusion method against selected bacterial and fungal pathogens. Results: Both aqueous and alcoholic extracts of P. pinnata demonstrated significant antimicrobial effects against the tested microbial species. The study highlights the potent antimicrobial properties of P. pinnata, attributed to its diverse phytochemical composition. Conclusion: The findings of this study underscore P. pinnata as a valuable source of natural antimicrobial agents. Its efficacy against AMR pathogens suggests its potential application in the development of new treatments for infectious diseases. P. pinnata holds promise for medicinal use, particularly in contexts where conventional antibiotics are ineffective.

Progress in Treatment and Diagnostics of Infectious Disease with Polymers.

In this era of advanced technology and innovation, infectious diseases still cause significant morbidity and mortality, which need to be addressed. Despite overwhelming success in the development of vaccines, transmittable diseases such as tuberculosis and AIDS remain unprotected, and the treatment is challenging due to frequent mutations of the pathogens. Formulations of new or existing drugs with polymeric materials have been explored as a promising new approach. Variations in shape, size, surface charge, internal morphology, and functionalization position polymer particles as a revolutionary material in healthcare. Here, an overview is provided of major diseases along with statistics on infection and death rates, focusing on polymer-based treatments and modes of action. Key issues are discussed in this review pertaining to current challenges and future perspectives.

Hypidone hydrochloride (YL-0919) protects mice from meningitis via Sigma1R-STAT1-NLRP3-GSDMD pathway

BackgroundA growing number of studies have found that antidepressants have anti-inflammatory effects while protecting nerves. Hypidone hydrochloride (YL-0919) is a novel highly selective 5-HT reuptake blocker. Our previous studies have demonstrated that YL-0919 exerts notable antidepressant- and anxiolytic-like as well as procognitive effects. However, whether YL-0919 can be used to treat inflammatory and infectious diseases remain unknown. In this study, we aimed to verify the anti-inflammatory effect of YL-0919 on bacterial meningitis and further explore the potential molecular mechanisms. MethodsWe performed the experiments on pneumococcal meningitis mice in vivo and S. pneumoniae infected macrophages/microglia in vitro, with or without YL-0919 treatment.Cognitive function was evaluated by open-field task, Morris water maze test, and novel object recognition test. Histopathological staining and immunofluorescence staining were used to detect the pathological damage of meningitis and NLRP3 inflammasome activation in microglia/macrophages. The expression of the STAT1/NLRP3/GSDMD signal pathway was measured by western blots. Proinflammatory cytokines associated with pyroptosis were detected by ELISA. ResultsYL-0919 protected mice from fatal pneumococcal meningitis, characterized by attenuated cytokine storms, decreased bacterial loads, improved neuroethology, and reduced mortality. NLRP3 plays a key role in the regulation of inflammation. When the underlying mechanisms were investigated, we found that YL-0919 inhibited the activation of NLRP3 via STAT1, and thus inhibited macrophages/microglia pyroptosis, resulting in downregulation of proinflammatory cytokines. In addition, Sigma1R was identified as a pivotal receptor that can be engaged by YL-0919 to inhibit NLRP3 activation and pyroptosis pathway in microglia/macrophages. ConclusionsThese results provide new insights into the mechanisms of inflammation regulation mediated by the antidepressant YL-0919. Moreover, targeting the STAT1/NLRP3 pyroptosis pathway is a promising strategy for the treatment of infectious diseases like bacterial meningitis.