Chinese Journal of Natural Medicines
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2017
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IF 1.667
Xiao-Xiao LU,Yi-Fan JIANG,Hong LI,Ying-Ye OU,Zhi-De ZHANG,Hong-Ye DI,Dao-Feng CHEN,Yun-Yi ZHANG
Lipopolysaccharides (LPS) contamination in herbal crude polysaccharides is inevitable. The present study was performed to explore the effect of polymyxin B on abolishing the influence of LPS contamination in mononuclear cells. LPS was pretreated with polymyxin B sulfate (PB) at different concentrations for 1, 5 or 24 h, and then used to stimulate RAW264.7 and mouse peritoneal macrophages (MPMs). The nitric oxide (NO) and tumor necrosis factor-α (TNF-α) in cell culture supernatant, as the indications of cell response, were assayed. Bupleurum chinensis polysaccharides (BCPs) with trace amount contamination of LPS was treated with PB. 30 μg·mL −1 of PB, treating LPS (10 and 1 000 ng·mL −1 in stimulating RAW264.7 and MPMs respectively) at 37 °C for 24 h, successfully abolished the stimulating effect of LPS on the cells. When the cells were stimulated with LPS, BCPs further promoted NO production. However, pretreated with PB, BCPs showed a suppression of NO production in MPMs and no change in RAW264.7. In the in vitro experiments, LPS contamination in polysaccharide might bring a great interference in assessing the activity of drug. Pretreatment with PB (30 μg·mL −1 ) at 37 °C for 24 h was sufficient to abolish the effects of LPS contamination (10 and 1 000 ng·mL −1 ).
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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
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2022
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IF 4.831
Zhen Liu,Yijie Shi,Chen Li,Wentong Hu,Zhiyi Yao
Polymyxin B (PMB) was an antibiotic with highly effective antibacterial effect but narrow safety interval, and its residues in food had attracted widespread attention. It was important to develop an accurate method for the rapid detection of PMB in animal foods. In this work, we had established a ratiometric sensing system based on the formation of supramolecular assemblies of pyrenyl probes, which were driven by the synergy of noncovalent forces such as multiple-electrostatic and π-π stacking interactions. Compared with the traditional fluorescence detection based on the single wavelength change, the present approach showing two-wavelength fluorescence response could reduce the interference of other factors making the experimental results more accurate. The sensor exhibited high sensitivity and selectivity with a low detection limit (28.3 nM). This method could be used to realize visual detection and had a visual detection limit of 1 μM. As we had learned yet, this was the first ratiometric sensor for PMB detection in aqueous solution. We believed all our preliminary would not only provide a complementary strategy for the detection of PMB, but also develop some new ideas for the construction of sensors for rapid antibiotic detection.
研究领域:
分析化学
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纳米技术
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生物技术
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食品安全
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BIOMEDICINE & PHARMACOTHERAPY
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2023
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IF 7.5
Chunxia Hu,Jinyong Zhang,Ruiqin Cui,Shiyi Liu,Ying Huang,Huan Zeng,Shumin Cheng,Guibao Zhou,Jingli Li,Longqin Sun,Yan Zhao,Xiao Wang,Jianhua Liu,Quanming Zou,Wei Huang
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. Our results showed that Lyb24 inhibits the translational levels of genes associated with the modification of lipid A. In addition, Lyb24 increases the permeability, disrupts the integrity and induces the depolarization of the membrane. We further found that both Lyb24 and PB could directly bind to AzoR and inhibit its activity. Structural analysis showed that Lyb24 binds to the isoalloxazine ring of flavin mononucleotide (FMN) through pi-pi stacking and loop η4 of AzoR. A pneumonia model was used to confirm that the activity against clinical PB-resistant Klebsiella pneumoniae was enhanced due to Lyb24 on PB. In conclusion, we provide a potential therapeutic regimen by combining Lyb24 and PB to treat Gram-negative-resistant bacterial infections. Our findings not only explain the synergistic effect of Lyb24, but also expand our knowledge on the mechanism of action of PB.
研究领域:
微生物学
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药理学
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传染病学
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JOURNAL OF CHEMICAL RESEARCH
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2020
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IF 0.593
Yan Qiao,Hongchao Geng,Ning Jiang,Xingqi Zhu,Chenyi Li,Qingyun Cai
Upconversion nanoparticles, Yb,Tm,Fe-doped NaYF4 nanoparticles, are synthesized and modified with polymyxin B for the selective detection of Gram-negative bacteria. Polymyxin B, a cyclic cationic antimicrobial peptide which can specifically bind to the lipopolysaccharides of cell wall of Gram-negative bacteria, such as Escherichia coli, is used to target and bind Gram-negative bacteria. The bacteria are then quantified by measuring the fluorescence intensity of the upconversion nanoparticle–bacteria complexes at 801 nm under 980 nm excitation. A limit of detection of 36 CFU/mL is achieved in the detection of Escherichia coli, and Escherichia coli in soybean milk is successfully detected. The limited autofluorescence and photobleaching properties of the upconversion nanoparticles make the proposed method useful for in vivo fluorescence imaging of Gram-negative bacteria.
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Nano Research
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2024
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IF 9.5
Liu Fang,Zou Lingyun,Chen Yongcheng,Liu Zuolong,Huang Yue,Jin Qiao,Ji Jian
Biofilm-associated bacterial infection brings serious threats to global public health owing to serious antibiotic resistance. It is urgently needed to develop innovative strategies to combat biofilm-associated bacterial infections. Polymyxins stand out as the last line of defense against Gram-negative bacteria. However, serious nephrotoxicity of polymyxins severely limits their clinical utility. Herein, a hypoxia-responsive liposome is designed as the nanocarrier of polymyxin B (PMB) to combat biofilms developed by Gram-negative bacteria. A metronidazole modified lipid (hypoxia-responsive lipid (HRLipid)) is synthesized to fabricate hypoxia-responsive liposomes (HRLip). PMB loaded hypoxia-responsive liposomes (HRL-PMB) is then prepared to mitigate the nephrotoxicity of PMB while preserving its excellent bactericidal activity. HRL-PMB shows very low hemolysis and cytotoxicity due to liposomal encapsulation of PMB. PMB can be readily released from HRL-PMB in response to hypoxic biofilm microenvironment, exerting its bactericidal activity to realize biofilm eradication. The excellent in vivo antibiofilm ability of HRL-PMB is confirmed by a Pseudomonas aeruginosa infected zebrafish model and a P. aeruginosa pneumonia infection model. Meanwhile, HRL-PMB can greatly reduce the nephrotoxicity of PMB after intravenous injection. The hypoxia-sensitive liposomes held great promise to improve the biosafety of highly toxic antibiotics while preserving their intrinsic bactericidal ability, which may provide an innovative strategy for combating biofilm-associated infections.
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Materials Today Bio
·
2025
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IF 10.2
Ziling Li,Huiling Lei,Jiannan Hu,Tong Zhou,Shuaiqi Yuan,Xinyue Ma,Yunfei Zhu,Chao Liu,Decai Wang,Yuzhou Wu,Shuyun Xu
The pneumonia induced by carbapenem resistant Klebsiella pneumoniae (CRKP) has high morbidity and mortality. Among the antibiotics currently available, polymyxin B (PMB) is considered to be the last line of defense. Routine intravenous administration of PMB has many problems, such as severe neurotoxicity and nephrotoxicity. In this study, a novel inhaled PMB-loaded albumin nanoparticles (PEG-pHSA@PMB) capable of penetrating airway mucus and responding to the infection microenvironment is constructed. An acid-responsive functional molecule (PEBA) and NH 2 -PEG-SH are linked to the surface of human serum albumin (HSA) via the conjugation reaction. Subsequently, PMB is loaded through electrostatic interactions to yield PEG-pHSA@PMB. The sulfhydryl groups of PEG-pHSA@PMB interact with mucins to help penetrate mucus after inhaled. In an acidic environment, the protonation of the tertiary amino groups within PEG-pHSA@PMB causes the charge alteration, which leads to the release of PMB. It demonstrated excellent mucus permeability, potent bactericidal activity, and superior bacteriostatic effects compared to sole PMB. Inhalation of PEG-pHSA@PMB significantly reduced the bacterial load in the lungs of mice with CRKP pneumonia, alleviating inflammatory response. Moreover, PEG-pHSA@PMB exhibited good cytocompatibility and biosafety. The novel strategy of the inhalation drug delivery system is promising for the treatment of pneumonia caused by drug-resistant bacteria.
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JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2024
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IF 9.4
Guoliang Cai,Ruifeng Li,Xubin Chai,Xiao Cai,Kaifeng Zheng,Yanyan Wang,Kelong Fan,Zhiping Guo,Jiancheng Guo,Wei Jiang
Diabetic wounds are characterized by chronic trauma , with long-term non-healing attributed to persistent inflammation and recurrent bacterial infections. Exacerbation of the inflammatory response is largely due to increased levels of reactive oxygen species (ROS). In this study, catalase (CAT) was used as a biological template to synthesize nanozyme-supported natural enzymes (CAT-Mn(SH) x ) using a biomimetic mineralization method. Subsequently, polymyxin B (CAT-Mn(SH) x @PMB) was immobilized on its surface through electrostatic assembly. CAT-Mn(SH) x @PMB demonstrates the ability for slow and sustained release of hydrogen sulfide (H 2 S). Finally, CAT-Mn(SH) x @PMB loaded microneedles (MNs) substrate were synthesized using polyvinyl alcohol (PVA) and hydroxyethyl methacrylate (HEMA), and named CAT-(MnSH) x @PMB-MNs. It exhibited enhanced enzyme and antioxidant activities , along with effective antibacterial properties. Validation findings indicate that it can up-regulate the level of M2 macrophages and reduce the level of pro-inflammatory cytokine tumor necrosis factor-α (TNF-α). Additionally, it promotes angiogenesis and rapid nerve regeneration, thereby facilitating wound healing through its dual anti-inflammatory and antibacterial effects . Hence, this study introduces a time–space tissue-penetrating and soluble microneedle patch with dual anti-inflammatory and antibacterial effects for the treatment of diabetic wounds.
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Biomaterials Science
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2026
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IF 5.7
Meilin Qiao,Licheng Gao,Ruibing Yu,Jian-Wei Chen,Xuanrong Sun,Yue Cai
The emergence of multidrug-resistant Pseudomonas aeruginosa (P. aeruginosa) infections, particularly those involving biofilm formation, poses a critical challenge to global healthcare. While polymyxin B (PMB) remains a last-line antibiotic against such infections, its efficacy is severely limited by poor biofilm penetration and adaptive resistance mechanisms. In this study, we developed a biomimetic nanoplatform (PMφ-PLGA-NOR) comprising a poly(lactic-co-glycolic acid) (PLGA) core loaded with norharmane (NOR), coated with PMB-modified P. aeruginosa cytoplasmic membrane (PMφ). This design utilizes the homologous targeting of bacterial membrane components and PMB's affinity for gram-negative pathogens to achieve efficient biofilm penetration. NOR, a βcarboline compound, has been shown to disrupt quorum sensing (QS) by inhibiting PqsA, resulting in significant reduction in biofilm formation. In vitro investigations have demonstrated that PMφ-PLGA-NOR disrupts the integrity of biofilms, thereby enhancing the bactericidal efficacy of PMB by facilitating its deep penetration into the biofilm matrix. In vivo, intraperitoneal administration of Mφ-PLGA-NOR combined with PMB achieved a 2-log reduction in bacterial lung burden. This study underscores the promise of bacterial plasma membrane-based pathogen-mimetic nanoplatforms in potentiating the efficacy of antibiotic adjuvants in conjunction with biofilmpenetrating strategies.
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Toxicology Research
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2026
·Vol. 15
·期 1
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IF 2.9
Yang Haoming,Yin Yuan,Wang Pengkai,Li Jiakai,Yuan Fang,Xiang Debiao,Deng Yang,Li Xin
Polymyxin B remains a first-line therapeutic option against Gram-negative bacterial infections; however, its clinical utility is substantially limited by dose-limiting toxicity, the mechanisms of which remain incompletely elucidated. Within a network toxicology framework, this study systematically investigated the potential toxic characteristics and underlying molecular mechanisms of Polymyxin B, with a specific focus on three key adverse effects: acute kidney injury, neurotoxicity, and skin pigmentation. Potential targets associated with Polymyxin B exposure and these toxicities were initially identified through integrated data mining of the SuperPred, SEA, GeneCards, and OMIM databases. A protein–protein interaction (PPI) network was subsequently constructed and analyzed using the STRING database and Cytoscape software. Functional enrichment analyses, including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses, were performed using Metascape. Furthermore, a compound–target–pathway network and Sankey diagram were generated to identify major active components, followed by molecular docking between these components and proteins encoded by the key targets. Molecular docking and molecular dynamics simulations confirmed strong binding affinities between Polymyxin B and core target proteins, namely STAT3, NF-κB, PRKACA, and HIF1A. Notably, both PMB1 and PMB2 exhibited high binding affinity for NF-κB. Consistent with these findings, in vivo studies in mice demonstrated that Polymyxin B treatment significantly enhanced the activation of the NF-κB pathway in renal tissues. Conversely, co-administration of the NF-κB pathway inhibitors PDTC and JSH-23 markedly attenuated Polymyxin B-induced nephrotoxicity. In conclusion, these experimental results indicate that hyperactivation of NF-κB is a critical mechanism underlying Polymyxin B-induced renal toxicity.
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MICROCHEMICAL JOURNAL
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2024
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IF 4.9
Liang Zhang,Rouying Cai,Yao Wang,Chenfang Miao,Menghan Zhang,Chen Zheng,Jianzhong Zhang,Zhengjun Huang,Shaohuang Weng
Low molecular weight heparin (LMWH) plays an important role in the prevention and treatment of venous thromboembolism. Sensitive and facile monitoring of LMWH is of great significance for clinical special populations. Herein, using enoxaparin (Enox) as the typical representative of LMWH, a convenient and accurate fluorescence method was developed for Enox detection using carbon dots with antioxidant activity (A-CDs) as probe and polymyxin B (PMB) as medium agent. Compared with the simple Enox or PMB, the formed complex of PMB and Enox (PMB-Enox) based on the electrostatic interaction exhibited a new absorbance peak at 340 nm. Correspondingly, the absorbance of PMB-Enox overlapped with the exciting wavelength of A-CDs at 350 nm and effectively quenched the fluorescence of A-CDs through inner filter effect (IFE). The decreased fluorescence intensities of A-CDs were controlled by the increased Enox with constant PMB. A linear fitting equation was obtained between the quenching efficiency (QE) of A-CDs and variable contents of Enox in the range of 0.8–25.0 μg/mL. And the limit of detection (LOD) was 0.64 μg/mL. The recovery of the injection of Enox in human plasma was acceptable with rational relative standard deviations. Moreover, this fluorescence sensing strategy possesses the prospect of developing reliable pharmaceutical analysis method based on the consideration of drug’s property and pharmacological action and the controllable design of fluorescence probes.
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Biomolecules
·
2025
·Vol. 15
·期 12
·1694
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IF 4.8
Siyu Huang,Xiaorui Li,Xin Lu,Biao Kan
Polymyxins, including polymyxin B (PMB), are last-resort antibiotics against multidrug-resistant Gram-negative infections in humans and livestock. Residual polymyxins from wastewater and manure can accumulate in soil, facilitating the emergence and spread of polymyxin resistance.Paenibacillus polymyxa, a natural polymyxin producer used in crop cultivation, may increase soil polymyxin burden. Since PMB strongly adsorbs to soil, its reliable quantification has been challenging. To address this, the extraction solvent and solid-phase extraction procedure were optimized to improve recovery and reduce matrix effects. We developed and validated a UPLC-MS/MS method to quantify PMB in soil. The method showed linearity (10–1000 ng/g), with a limit of detection of 0.86 ng/g and a limit of quantification of 2.12 ng/g. Method validation confirmed acceptable analytical performance. A 28-day monitoring of PMB in soil inoculated with varyingP. polymyxadoses revealed a dose-dependent increase over the first 14 days, followed by a decline; PMB remained detectable on day 28. Ecological risk assessment using the risk quotient (RQ) indicated that PMB levels in the high-dose group (2 × 108CFU/100 g) approached the high-risk threshold (RQ ≥ 1) on day 14, while lower doses posed low to medium risk. This work provides a soil PMB quantification method and insight into the ecological risk ofP. polymyxaapplication.
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Science Bulletin
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2023
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IF 18.9
Yue Zhou,Jiayuan Huang,Guanlin Wang,Zizhao Zhai,Maizbha Uddin Ahmed,Xiao Xia,Cenfeng Liu,Yuzhen Jin,Xin Pan,Ying Huang,Chuanbin Wu,Xuejuan Zhang
Pulmonary infections caused by multidrug-resistant bacteria have become a significant threat to human health. Bacterial biofilms exacerbate the persistence and recurrence of pulmonary infections, hindering the accessibility and effectiveness of antibiotics. In this study, a dry powder inhalation (DPI) consisting of polymyxin B sulfate (PMBS) inhalable microparticles and high-lectin-affinity (HLA) sugar (i.e., raffinose) carriers was developed for treating pulmonary infections and targeting bacterial lectins essential for biofilm growth. The formulated PMBS-HLA DPIs exhibited particle sizes of approximately 3 μm, and surface roughness varied according to the drug-to-carrier ratio. Formulation F5 (PMBS: raffinose = 10: 90) demonstrated the highest fine particle fraction (FPF) value (64.86%), signifying its substantially enhanced aerosol performance, potentially attributable to moderate roughness and smallest mass median aerodynamic particle size. The efficacy of PMBS-HLA DPIs in inhibiting biofilm formation and eradicating mature biofilms was significantly improved with the addition of raffinose, suggesting the effectiveness of lectin-binding strategy for combating bacterial biofilm-associated infections. In rat models with acute and chronic pulmonary infections, F 5 demonstrated superior bacterial killing and amelioration of inflammatory responses compared to spray-dried PMBS (F 0 ). In conclusion, our HLA carrier-based formulation presents considerable potential for the efficient treatment of multidrug-resistant bacterial biofilm-associated pulmonary infections.
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