mRNA-based platform for preventing and treating by targeted staphylococcal enterotoxin B.

() possesses numerous virulence factors, with the increasing prevalence of drug-resistant strains heightening the threat posed by this pathogen. Staphylococcal enterotoxin B (SEB), a highly conserved toxin secreted by , is also recognized as a potential bioweapon with super-antigenic activity. SEB represents a promising target in efforts to combat infections caused by .

A chitosan-modified tea tree oil self-nanoemulsion improves antibacterial effects in vivo and in vitro and promotes wound healing by influencing metabolic processes against multidrug-resistant bacterial infections.

Infectious diseases, especially multidrug-resistant bacterial infections, have caused crises and majorly disrupted public health and economic stability worldwide. Many natural essential oils, especially tea tree oil, have potential to treat multidrug-resistant bacteria, such as H. pylori and P.

Vaccination with a trivalent Klebsiella pneumoniae vaccine confers protection in a murine model of pneumonia.

Klebsiella pneumoniae (K. pneumoniae) is an opportunistic pathogen and the major cause of healthcare-associated infections, which are increasingly complicated by the prevalence of highly invasive and hyper-virulent K. pneumoniae strains, necessitating the development of alternative strategies for combatting infections caused by this bacterium.

Asymmetric total synthesis of polycyclic xanthenes and discovery of a WalK activator active against MRSA.

The development of new antibiotics continues to pose challenges, particularly considering the growing threat of multidrug-resistant Staphylococcus aureus. Structurally diverse natural products provide a promising source of antibiotics. Herein, we outline a concise approach for the collective asymmetric total synthesis of polycyclic xanthene myrtucommulone D and five related congeners.

A highly neutralizing human monoclonal antibody targeting a novel linear epitope on staphylococcal enterotoxin B.

Staphylococcal Enterotoxin B (SEB), produced by (), is a powerful superantigen that induces severe immune disruption and toxic shock syndrome (TSS) upon binding to MHC-II and TCR. Despite its significant impact on the pathogenesis of , there are currently no specific therapeutic interventions available to counteract the mechanism of action exerted by this toxin. In this study, we have identified a human monoclonal antibody, named Hm0487, that specifically targets SEB by single-cell sequencing using PBMCs isolated from volunteers enrolled in a phase I clinical trial of the five-antigen vaccine.

Type VII secretion system extracellular protein B targets STING to evade host anti- immunity.

() can evade antibiotics and host immune defenses by persisting within infected cells. Here, we demonstrate that in infected host cells, type VII secretion system (T7SS) extracellular protein B (EsxB) interacts with the stimulator of interferon genes (STING) protein and suppresses the inflammatory defense mechanism of macrophages during early infection. The binding of EsxB with STING disrupts the K48-linked ubiquitination of EsxB at lysine 33, thereby preventing EsxB degradation.

A novel member of drug/metabolite transporter (DMT) family efflux pump, SA00565, contributes to tetracycline antibiotics resistance in USA300.

Drug efflux systems have recently been recognized as a significant mechanism responsible for multidrug resistance in bacteria. In this study, we described the identification and characterization of a new chromosomally encoded efflux pump (SA00565) in . SA00565, which belongs to the drug/metabolite transporter (DMT) superfamily, was predicted to be a 10-transmembrane segment transporter.

A rational designed multi-epitope vaccine elicited robust protective efficacy against Klebsiella pneumoniae lung infection.

Background: The emergence of drug-resistant strains of Klebsiella pneumoniae (K. pneumoniae) has become a significant challenge in the field of infectious diseases, posing an urgent need for the development of highly protective vaccines against this pathogen.

Methods And Results: In this study, we identified three immunogenic extracellular loops based on the structure of five candidate antigens using sera from K.

CD39 expression defines exhausted CD4 T cells associated with poor survival and immune evasion in human gastric cancer.

Objectives: CD4 T cell helper and regulatory function in human cancers has been well characterised. However, the definition of tumor-infiltrating CD4 T cell exhaustion and how it contributes to the immune response and disease progression in human gastric cancer (GC) remain largely unknown.

Methods: A total of 128 GC patients were enrolled in the study.

pGM-CSF as an adjuvant in DNA vaccination against SARS-CoV-2.

The emergence of SARS-CoV-2 presents a significant global public health dilemma. Vaccination has long been recognized as the most effective means of preventing the spread of infectious diseases. DNA vaccines have attracted attention due to their safety profile, cost-effectiveness, and ease of production.

CD39 identifies an exhausted tumor-reactive CD8 T cell population associated with tumor progression in human gastric cancer.

The ectonucleotidase CD39 has been regarded as a promising immune checkpoint in solid tumors. However, the expression of CD39 by tumor-infiltrating CD8 T cells as well as their potential roles and clinical implications in human gastric cancer (GC) remain largely unknown. Here, we found that GC-infiltrating CD8 T cells contained a fraction of CD39 cells that constituted about 6.

Dronedarone Enhances the Antibacterial Activity of Polymyxin B and Inhibits the Quorum Sensing System by Interacting with LuxS.

Quorum sensing (QS) is considered an appealing target for interference with bacterial infections. β-Adrenergic blockers are promising anti-QS agents but do not have antibacterial activity. We assessed the potential ability of adrenergic receptor inhibitors to enhance the antibacterial activity of polymyxin B (PB) against and determined that dronedarone has the most potent activity both and .

Unveiling the fructose metabolism system in Staphylococcus aureus: insights into the regulatory role of FruR and the FruRKT operon in bacterial fitness.

Background: The utilization of fructose as a carbon source and energy provider plays a crucial role in bacterial metabolism. Additionally, fructose metabolism directly impacts the pathogenicity and virulence of certain pathogenic microorganisms.

Results: In this study, we report the discovery of a fructose phosphotransferase system (PTS) in S.

Antibody-antibiotic conjugate targeted therapy for orthopedic implant-associated intracellular S. aureus infections.

Introduction: Treating orthopedic implant-associated infections, especially those caused by Staphylococcus aureus (S. aureus), remains a significant challenge. S.

Human monoclonal antibodies against Staphylococcus aureus A protein identified by high-throughput single-cell sequencing of phase I clinical volunteers' B cells.

Methicillin-resistant Staphylococcus aureus, poses a significant threat through infections in both community and hospital settings. To address this challenge, we conducted a phase I clinical trial study involving a recombinant Staphylococcus aureus vaccine. Utilizing peripheral blood lymphocytes from 64 subjects, we isolated antigen-specific memory B cells for subsequent single-cell sequencing.

The enhancement effect of small molecule Lyb24 reveals AzoR as a novel target of polymyxin B.

Given the important role of polymyxin B (PB) in the treatment of drug-resistant Gram-negative bacterial infections, the emergence of PB resistance poses a serious threat to public health. Adjuvant development is a supplementary strategy that can compensate for the lack of novel antibiotics by protecting PB. In this study, we found a small molecule named Lyb24 that showed weak antibacterial activity (minimum inhibitory concentration ≥ 10 μg/ml) but potentiated and revitalized the efficacy of PB against Gram-negative pathogens, including mcr-1- and mgrB-deletion-mediated PB-resistant strains.

Structural and biological insights into outer membrane protein lipotoxin F of Pseudomonas aeruginosa: Implications for vaccine application.

Due to the increasing antibiotic resistance of Pseudomonas aeruginosa (PA), an effective vaccine is urgently needed. However, no PA vaccine has been approved to date, and new protective antigens are needed to improve their efficacy. In this study, Luminex beads were used to identify new candidate antigens, after which their crystal structure was determined, and their potential contribution to bacterial pathogenesis was assessed in vitro and in vivo.

Recombinant Pseudomonas aeruginosa flagellin delivered using ferritin nanoparticles provides enhanced cross-protection against lung infection in mice.

Increasing prevalence of multidrug- and pan-drug-resistant Pseudomonas aeruginosa (PA) strains has created an urgent need for an effective vaccine. Flagellin is an essential vaccine target because of its contribution to bacterial motility and other pathogenic processes. However, flagellin-based vaccines have not been successful thus far, probably due to a lack of efficient adjuvants or delivery systems.

rFSAV promotes Staphylococcus aureus-infected bone defect healing via IL-13- mediated M2 macrophage polarization.

Staphylococcus aureus (S. aureus) contamination commonly occurs in orthopedic internal fixation operations, leading to a delayed healing of the defected bone tissue. However, antibiotic treatments are ineffective in dealing with S.

The safety and immunogenicity of a recombinant five-antigen Staphylococcus aureus vaccine among patients undergoing elective surgery for closed fractures: A randomized, double-blind, placebo-controlled, multicenter phase 2 clinical trial.

Background: Vaccines are urgently required to control Staphylococcus aureus hospital and community infections and reduce the use of antibiotics. Here, we report the safety and immunogenicity of a recombinant five-antigen Staphylococcus aureus vaccine (rFSAV) in patients undergoing elective surgery for closed fractures.

Methods: A randomized, double-blind, placebo-controlled, multicenter phase 2 clinical trial was carried out in 10 clinical research centers in China.

Self-assembled ferritin nanoparticles displaying PcrV and OprI as an adjuvant-free vaccine.

Introduction: Serious infections of (PA) in hospitals and the emergence and increase of multidrug resistance have raised an urgent need for effective vaccines. However, no vaccine has been approved to date. One possible reason for this is the limited immune response due to the lack of an efficient delivery system.