Effect of daphnetin, the coumarin derivative isolated from Daphne genus, on Helicobacter pylori adhesion to gastric epithelial cells.

Background: Adherence of Helicobacter pylori to the surface of the gastric mucosa is the initial and crucial step for its survival and colonization in the harsh conditions of the stomach. We had previously demonstrated that daphnetin has anti-adhesion effect.

Purpose: This study aims to explore the mechanisms of daphnetin to reduce H.

High level non-carbapenemase carbapenem resistance by overlaying mutations of , and in .

Unlabelled: Carbapenem-resistant (CRPA) is a global threat, but the mechanism of non-carbapenemase carbapenem resistance is still unclear. In the current study, we investigated the contributions of point mutations in , , and to carbapenem resistance in during evolution studies with consecutive clinical isolates. Real-time qPCR and Electrophoretic Mobility Shift Assay demonstrated that MexR (Gln55Pro) mutation increased MexAB efflux pump genes expression by altering MexR's binding capacity, leading to a four- to eight-fold increase in meropenem MIC in the Pae d1 Green ∆ and PAO1∆ mutants.

Non-antibiotic pharmaceutical phenylbutazone binding to MexR reduces the antibiotic susceptibility of Pseudomonas aeruginosa.

Antimicrobial resistance has been an increasingly serious threat to global public health. The contribution of non-antibiotic pharmaceuticals to the development of antibiotic resistance has been overlooked. Our study found that the anti-inflammatory drug phenylbutazone could protect P.

Negatively charged nanodiscs for the reduction of toxicity and enhanced efficacy of polymyxin B against Acinetobacter baumannii sepsis.

The treatment of sepsis caused by multidrug-resistant (MDR) Gram-negative bacterial infections remains challenging. With these pathogens exhibiting resistance to carbapenems and new generation cephalosporins, the traditional antibiotic polymyxin B (PMB) has reemerged as a critical treatment option. However, its severe neurotoxicity and nephrotoxicity greatly limit the clinical application.

The Prediction of LptA and LptC Protein-Protein Interactions and Virtual Screening for Potential Inhibitors.

Antibiotic resistance in Gram-negative bacteria remains one of the most pressing challenges to global public health. Blocking the transportation of lipopolysaccharides (LPS), a crucial component of the outer membrane of Gram-negative bacteria, is considered a promising strategy for drug discovery. In the transportation process of LPS, two components of the LPS transport (Lpt) complex, LptA and LptC, are responsible for shuttling LPS across the periplasm to the outer membrane, highlighting their potential as targets for antibacterial drug development.

Deletion of the gene leads to changes in membrane-related lipid composition and antibiotic susceptibility.

Introduction: (), the main cause of tuberculosis (TB), has brought a great burden to the world's public health. With the widespread use of drug-resistant strains, the pressure on anti-TB treatment is increasing. Anti-TB drugs with novel structures and targets are urgently needed.

Discovery of Gambogic acid as an antibacterial adjuvant against vancomycin-resistant enterococci in vitro and in vivo.

Background: The emergence and spread of vancomycin-resistant enterococci (VRE) have posed a significant challenge to clinical treatment, underscoring the need to develop novel strategies. As therapeutic options for VRE are limited, discovering vancomycin enhancer is a feasible way of combating VRE. Gambogic acid (GA) is a natural product derived from the resin of Garcinia hanburyi Hook.

Subplenones A-J: Dimeric Xanthones with Antibacterial Activity from the Endophytic Fungus sp. CPCC 401465.

Subplenones A-J (-), 10 new xanthone dimers, have been isolated and characterized from the endophytic fungus sp. CPCC 401465, which resides within the Chinese medicinal plant . The isolation process was guided by antibacterial assays and molecular-networking-based analyses.

Synthesis of peptidomimetics as antibiotic adjuvants for combination with aztreonam to combat MDR Pseudomonas aeruginosa.

Pseudomonas aeruginosa is one of the multipledrug-resistant (MDR) Gram-negative pathogens with few drugs available for treatment. Antibiotic adjuvant approach provides an alternative and complementary strategy. In this study, the stereo-structure-activity relationship of monobactams against MDR Gram-negative organisms was extended.

Evolution and development of potent monobactam sulfonate candidate IMBZ18g as a dual inhibitor against MDR Gram-negative bacteria producing ESBLs.

A series of new monobactam sulfonates is continuously synthesized and evaluated for their antimicrobial efficacies against Gram-negative bacteria. Compound (IMBZ18G) is highly effective and against clinically intractable multi-drug-resistant (MDR) Gram-negative strains, with a highly druglike nature. The checkerboard assay reveals its significant synergistic effect with -lactamase inhibitor avibactam, and the MIC values against MDR were reduced up to 4-512 folds X-ray co-crystal and chemoproteomic assays indicate that the anti-MDR bacteria effect of results from the dual inhibition of the common PBP3 and some class A and C -lactamases.

In vivo pharmacodynamic study of contezolid acefosamil, a prodrug of contezolid for oral and intravenous administration.

Objectives: Contezolid acefosamil is a novel O-acyl phosphoramidate prodrug of contezolid. In the current study, we aimed to systemically evaluate the efficacy of contezolid acefosamil against infections caused by multiple Gram-positive pathogens, and compare the efficacy of the prodrug by oral and intravenous administrations.

Methods: The in vivo pharmacodynamic efficacy of contezolid acefosamil was evaluated in mouse models of systemic (with five S.

Isolation, Structure Elucidation, and First Total Synthesis of Quinomycins K and L, Two New Octadepsipeptides from the Maowei Sea Mangrove-Derived sp. B475.

Mangrove actinomycetia have been proven to be one of the promising sources for discovering novel bioactive natural products. Quinomycins K () and L (), two rare quinomycin-type octadepsipeptides without intra-peptide disulfide or thioacetal bridges, were investigated from the Maowei Sea mangrove-derived sp. B475.

Identification and Quantification of S-Sulfenylation Proteome of Mycobacterium tuberculosis under Oxidative Stress.

The ability to maintain redox homeostasis is critical for Mycobacterium tuberculosis () to survive the redox stress of the host. There are many antioxidant systems in to ensure its normal replication and survival in the host, and cysteine thiols are one of them. S-sulfenylation is one of the reversible modifications of cysteine thiols to resist oxidative stress.

Iterative Methylation Leads to 3-Methylchuangxinmycin Production in CPCC 200056.

A new congener of chuangxinmycin (CM) was identified from CPCC 200056. Its structure was determined as 3-methylchuangxinmycin (MCM) by 1D and 2D NMR. MCM could be generated from CM by heterologous expression of the vitamin B-dependent radical SAM enzyme CxnA/A responsible for methylation of 3-demethylchuangxinmycin (DCM) in CM biosynthesis, indicating that CxnA/A could perform iterative methylation for MCM production.

Antibacterial Activity of an FtsZ Inhibitor Celastrol and Its Synergistic Effect with Vancomycin against Enterococci and .

Enterococci can cause various infectious diseases, including urinary tract infection, wound infection, and life-threatening endocarditis and meningitis. The emergence and transmission of vancomycin-resistant enterococci (VRE) have presented a challenge to clinical treatment. There is an urgent need to develop new strategies to fight against this pathogen.

ML364 exerts the broad-spectrum antivirulence effect by interfering with the bacterial quorum sensing system.

Antivirulence strategy has been developed as a nontraditional therapy which would engender a lower evolutionary pressure toward the development of antimicrobial resistance. However, the majority of the antivirulence agents currently in development could not meet clinical needs due to their narrow antibacterial spectrum and limited indications. Therefore, our main purpose is to develop broad-spectrum antivirulence agents that could target on both Gram-positive and Gram-negative pathogens.

The Anti-Multidrug-Resistant Study on 1,3-diamino-7H-pyrrolo[3,2-f]quinazoline Compounds.

As a major public health problem, the prevalence of () infections in hospitals due to the pathogen's multiple-antibiotic resistance has attracted extensive attention. We previously reported a series of 1,3-diamino-7H-pyrrolo[3,2-f]quinazoline (PQZ) compounds, which were designed by targeting dihydrofolate reductase (DHFR), and exhibited potent antibacterial activities. In the current study, based on our molecular-modeling study, it was proposed that PQZ compounds may function as potent DHFR (DHFR)-inhibitors as well, which inspired us to consider their anti- abilities.

Evaluation of Agar Dilution Method in Susceptibility Testing of Polymyxins for Enterobacteriaceae and Non-Fermentative Rods: Advantages Compared to Broth Microdilution and Broth Macrodilution.

An accurate and reliable susceptibility testing method for polymyxins is urgently needed not only for the clinical laboratory but also for new polymyxin-like lipopeptide development. Reference broth microdilution (rBMD), which was the recommended method by CLSI-EUCAST in clinics, has been proven not to be ideal, while the agar dilution (AD) method that was widely used in new antibiotics discovery has been neglected. In the present study, the AD method was compared with rBMD and broth macrodilution (BMAD) in susceptibility testing of polymyxin B and colistin against >200 Gram-negative isolates.

Discovery of -quinazolinone-4-hydroxy-2-quinolone-3-carboxamides as DNA gyrase B-targeted antibacterial agents.

Emerging drug resistance is generating an urgent need for novel and effective antibiotics. A promising target that has not yet been addressed by approved antibiotics is the bacterial DNA gyrase subunit B (GyrB), and GyrB inhibitors could be effective against drug-resistant bacteria, such as methicillin-resistant (MRSA). Here, we used the 4-hydroxy-2-quinolone fragment to search the Specs database of purchasable compounds for potential inhibitors of GyrB and identified or , as a novel and potent inhibitor of the target protein (IC: 1.

Roles of cysteine in the structure and metabolic function of CYP142A1.

CYP142A1 is a cytochrome P450 (CYP) enzyme expressed in (), which supports the growth of H37Rv relying on cholesterol, in the absence of CYP125A1. Since cysteine residues usually play a fundamental role in maintaining the structure and function of CYP enzymes, in this study, we aimed to determine the potential biochemical functions of six cysteine residues except for the heme-binding cysteine in the amino acid sequence of recombinant CYP142A1 by replacing each one using site-directed mutagenesis. Recombinant CYP142A1 mutants were heterologously expressed, purified, and analyzed using ESI-MS, far-UV CD spectroscopy, UV-vis spectrophotometric titration, and metabolic function assays.

Synthesis and biological evaluation of novel N, N'-diarylurea derivatives as potent antibacterial agents against MRSA.

A series of new N, N'-diarylurea derivatives were designed and synthesized, some of which exhibited potent antibacterial activity against the drug-susceptible and drug-resistant Gram-positive strains. Especially, compounds 2c, 2g-2l showed broader antibacterial spectrum and more potent antibacterial activity (MIC = 0.30-2.

Effect of Different Tolerable Levels of Constitutive Expression on Escherichia coli.

To study the effect of different tolerable levels of constitutive expression on Escherichia coli, and to provide direct evidence for moderate resistance mediated by , construction of E. coli strains carrying on the chromosome with promoters of different strengths was conducted using λ-red recombination. Our results demonstrated that over-high expression of cannot be tolerated, and seven constructs with more than 200-fold transcriptional expression differences were obtained.