JOURNAL OF HAZARDOUS MATERIALS
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2021
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IF 10.588
Shuai Wang,Wei Shi,Zhichu Huang,Nihong Zhou,Yanling Xie,Yu Tang,Fuliang Hu,Guangxu Liu,Huoqing Zheng
Biodegradation of plastic polymers by plastic-eating insects such as the greater wax moth ( Galleria mellonella ) might be promising for reducing plastic pollution, but direct in vivo evidence along with the related metabolic pathways and role of gut microbiota require further investigation. In this study, we investigated the in vivo degradation process, underlying potential metabolic pathways, and involvement of the gut microbiota in polystyrene (PS) biodegradation via enforcing injection of G. mellonella larvae (Tianjin, China) with PS microbeads (0.5 mg/larva; M n : 540 and M w : 550) and general-purpose PS powders (2.5 mg/larva; M n : 95,600 and M w : 217,000). The results indicated that the PS microplastics were depolymerized and completely digested independent of gut microbiota in G. mellonella although the metabolism could be enhanced by gut microbiota. Based on comparative metabolomic and liquid chromatography analyses, we proposed two potential metabolic pathways of PS in the intestine of G. mellonella larvae: the styrene oxide–phenylacetaldehyde and 4-methylphenol–4-hydroxybenzaldehyde–4-hydroxybenzoate pathways. These results suggest that the enzymes of G. mellonella are responsible for the efficient biodegradation of PS. Further study is needed to identify these enzymes and investigate the underlying catalytic mechanisms.
研究领域:
环境科学
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微生物学
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生物化学
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产品关联
DOI
PubMed
高影响因子
Journal of Advanced Research
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2021
·
IF 10.479
Xueyang Jin,Ming Zhang,Jinghui Lu,Ximeng Duan,Jinyao Chen,Yue Liu,Wenqiang Chang,Hongxiang Lou
Introduction The increasing morbidity of fungal infections and the prevalence of drug resistance highlighted the discovery of novel antifungal agents and investigation of their modes of action. Iron chelators have been used to treat superficial fungal infections or potentiate the efficacy of certain antifungal drugs. Hinokitiol exhibits potent antifungal activity and iron-chelating ability. However, their relationships have not been established. Objectives This study aims to explore the selectivity of hinokitiol against fungal cells and mammalian cells and determine the role of iron-chelating for the antifungal activity of hinokitiol. Methods Iron probe FeRhonox-1 was used to determine intracellular Fe 2+ content. 5-Cyano-2,3-ditolyl tetrazolium chloride probe and Cell Counting Kit-8 were used to detect the mitochondrial respiratory activities. Quantitative real-time PCR and rescue experiments were performed to determine the effect of iron on the antifungal activity of hinokitiol. The effects of hinokitiol on fungal mitochondria were further evaluated using reactive oxygen species probes and several commercial Assay Kits. The ability of hinokitiol to induce resistance in Candida species was carried out using a serial passage method. The in vivo therapeutic effect of hinokitiol was evaluated using Galleria mellonella as an infectious model. Results Hinokitiol was effective against a panel of Candida strains with multiple azole-resistant mechanisms and persistently inhibited Candida albicans growth. Mechanism investigations revealed that hinokitiol chelated fungal intracellular iron and inhibited the respiration of fungal cells but had minor effects on mammalian cells. Hinokitiol further inhibited the activities of mitochondrial respiratory chain complexes I and II and reduced mitochondrial membrane potential, thereby decreasing intracellular ATP synthesis and increasing detrimental intracellular reductive stress. Moreover, hinokitiol exhibited low potential for inducing resistance in several Candida species and greatly improved the survival of Candida -infected Galleria mellonella . Conclusions These findings suggested the potential application of hinokitiol as an iron chelator to treat fungal infections.
研究领域:
微生物学
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药理学
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真菌学
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医学真菌学
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产品关联
DOI
PubMed
高影响因子
Microbiology Spectrum
·
2022
·Vol. 10
·期 4
·
IF 9.043
Liping Li,Hui Lu,Xuan Zhang,Malcolm Whiteway,Hao Wu,Shanlun Tan,Jianye Zang,Shujuan Tian,Cheng Zhen,Xianlei Meng,Wanqian Li,Dazhi Zhang,Min Zhang,Yuanying Jiang
Baicalein (BE) is a promising antifungal small-molecule compound with an extended antifungal spectrum, good synergy with fluconazole, and low toxicity, but its target protein and antifungal mechanism remain elusive. In this study, we found that BE can function against Candida albicans by disrupting glycolysis through targeting Eno1 and inhibiting its function. Eno1 acts as a key therapeutic target of the drug, as BE had no antifungal activity against the eno1 null mutant in a Galleria mellonella model of C. albicans infection. To investigate the mechanism of action, we solved the crystal structure of C. albicans Eno1(CaEno1) and then compared the difference between this structure and that of Eno1 from humans. The predicted primary binding site of BE on CaEno1 is between amino acids D261 and W274, with D263, S269, and K273 playing critical roles in the interaction with BE. Both positions S269 and K273 have different residues in the human Eno1 (hEno1). This finding suggests that BE may bind selectively to CaEno1, which would limit the potential for side effects in humans. Our findings demonstrate that Eno1 is a target protein of BE and thus may serve as a novel target for the development of antifungal therapeutics acting through the inhibition of glycolysis.IMPORTANCE Baicalein (BE) is a promising antifungal agent which has been well characterized, but its target protein is still undiscovered. The protein Eno1 plays a crucial role in the survival of Candida albicans. However, there are few antifungal agents which inhibit the functions of Eno1. Here, we found that BE can function against Candida albicans by disrupting glycolysis through targeting Eno1 and inhibiting its function. We further solved the crystal structure of C. albicans Eno1(CaEno1) and predicted that the primary binding site of BE on CaEno1 is between amino acids D261 and W274, with D263, S269, and K273 playing critical roles in the interaction with BE. Our findings will be helpful to get specific small-molecule inhibitors of CaEno1 and open the way for the development of new antifungal therapeutics targeted at inhibiting glycolysis.
研究领域:
微生物学
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药理学
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分子生物学
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结构生物学
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DOI
高影响因子
JOURNAL OF BACTERIOLOGY
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2023
·Vol. 205
·期 8
·
IF 3.2
Meng-na Zhang,Xiao-ou Zhao,Qi Cui,Dao-mi Zhu,Muhammad Asif Wisal,Han-dong Yu,Ling-cong Kong,Hong-xia Ma
The development of novel antibiotic adjuvants is imminent because of the frequent emergence of resistance in Gram-negative bacteria, which severely restricts the efficiency and longevity of commonly used clinical antibiotics. It is reported that famotidine, a clinical inhibitor of gastric acid secretion, enhances the antibacterial activity of rifamycin antibiotics, especially rifampicin, against Gram-negative bacteria and reverses drug resistance. Studies have shown that famotidine disrupts the cell membrane of Acinetobacter baumannii and inhibits the expression of the outer membrane protein ompA gene, while causing a dissipation of the plasma membrane potential, compensatively upregulating the pH gradient and ultimately increasing the accumulation of reactive oxygen species by leading to increased bacterial mortality. In addition, famotidine also inhibited the efflux pump activity and the biofilm formation of A. baumannii. In the Galleria mellonella and mouse infection models, the combination of famotidine and rifampicin increased the survival rate of infected animals and decreased the bacterial load in mouse organs. In conclusion, famotidine has the potential to be a novel rifampicin adjuvant, providing a new option for the treatment of clinical Gram-negative bacterial infections.IMPORTANCE In this study, famotidine was discovered for the first time to have potential as an antibiotic adjuvant, enhancing the antibacterial activity of rifamycin antibiotics against A. baumannii and overcoming the limitations of drug therapy. With the discovery of novel applications for the guanidine-containing medication famotidine, the viability of screening prospective antibiotic adjuvants from guanidine-based molecules was further explored. In addition, famotidine exerts activity by affecting the OmpA protein of the cell membrane, indicating that this protein might be used as a therapeutic drug target to treat A. baumannii infections.
研究领域:
微生物学
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药理学
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传染病
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抗菌素耐药性
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DOI
PubMed
高影响因子
Journal of Global Antimicrobial Resistance
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2023
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IF 4.6
Jingchun Kong,Yue Wang,Yijia Han,Huijing Zhou,Zhenyun Huang,Xiaodong Zhang,Cui Zhou,Tieli Zhou,Jianming Cao
Objectives The emergence of carbapenem-resistant Escherichia coli (CREC) is a global concern as its prevalence restricts treatment options and poses a considerable threat to public health. In this study, in vitro and in vivo activity of the antimicrobial peptide Octominin against CREC were evaluated, and investigated its possible mechanism of action was investigated. Furthermore, its safety and factors influencing its antibacterial effect were assessed. Additionally, the anti-inflammatory effects of Octominin were examined. Methods The antimicrobial activity of Octominin against 11 strains of CREC was determined using the broth microdilution method, growth curve, and time-kill assay. Its possible mechanism of action was unraveled using the propidium iodide and N-phenyl-1-naphthylamine fluorochrome and lipopolysaccharide-binding assays. To understand the safety and stability of Octominin, its cytotoxicity, hemolysis, and antibacterial activity under various conditions, such as temperature and ions, were estimated. Additionally, a Galleria mellonella infection model was utilized to evaluate the efficacy of Octominin in vivo , and qRT-PCR was performed to assess its impact on the expression of proinflammatory cytokines. Results Octominin displayed a significant antibacterial effect, with MICs of 4 to 8 μg/mL and MBCs of 8 to 16 μg/mL. Octominin exerted its antibacterial effect by disrupting bacterial membranes. Cytotoxicity and hemolysis tests demonstrated the potential application of Octominin in vivo . The G. mellonella infection model asserted the in vivo efficacy of Octominin. Furthermore, Octominin inhibited the expression of proinflammatory cytokines. Although the temperature had little effect on its the activity, serum and ions reduced activity. Conclusions Octominin is a promising alternative agent with remarkable antibacterial and anti-inflammatory effects for treating infections caused by CREC .
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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免疫学
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DOI
PubMed
高影响因子
MICROBIAL PATHOGENESIS
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2025
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IF 3.5
Daxing Cao,Guihua Liu,Ying Wang,Xiaoxue Xia
Antibiotic resistance has become a significant global public health challenge, particularly in general surgery, where infections caused by resistant bacteria complicate treatment. This study aims to evaluate the potential of the FDA-disapproved antihistamine astemizole as an antibacterial agent, with a focus on its efficacy against methicillin-resistant S . aureus (MRSA). Astemizole demonstrated significant activity against Gram-positive bacteria, especially MRSA, with MIC and MBC values ranging from 4 to 16 μg/mL and 4–32 μg/mL, respectively. However, astemizole showed minimal activity against Gram-negative bacteria. Further investigations revealed that astemizole killed bacteria by disrupting the bacterial membrane, altering membrane potential, inhibiting ATP production, and inducing reactive oxygen species accumulation. Additionally, The resistance mutation frequency of astemizole was low, with only a minor increase in resistance observed in MRSA after 30 days of selective pressure, significantly less than that of ampicillin. Cytotoxicity and hemolysis assays indicated that astemizole was relatively safe at concentrations effective for bacterial inhibition. The Galleria mellonella infection model further confirmed the efficacy of astemizole against MRSA in vivo . Overall, this study provides new insights into the repurposing of astemizole and suggests its potential as a therapeutic agent to address antibiotic resistance.
研究领域:
药理学
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微生物学
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传染病学
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外科学
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产品关联
DOI
PubMed
高影响因子
MEDICAL MICROBIOLOGY AND IMMUNOLOGY
·
2025
·Vol. 214
·期 1
·1-13
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IF 3
Ding Zhi-Wen,Xu Kai-Zhong,Dar Owias Iqbal,Yin Lu-Jun,Wang Ying-Jie,Liao Yun-tong,Wang Peng,Jia Ai-Qun
Burkholderia cenocepacia , an opportunistic pathogen, poses a significant threat to human health, necessitating the discovery of effective quorum sensing inhibitors (QSIs). In this study, the quorum sensing inhibitory effects of deferiprone (DFP) on the B. cenocepacia 162,638 were validated. Notably, DFP demonstrated an ability to inhibit and disrupt bacterial biofilms, reducing biofilm formation by 44.59% at 1/4 MIC (minimum inhibitory concentration) and 24.32% at 1/8 MIC concentrations. The study also investigated DFP’s impact on motility, virulence, and QS signal levels. LC-MS/MS analysis showed a gradual reduction in the QS molecule C6-HSL as DFP concentrations increased. Additionally, DFP’s non-hemolytic properties and safety profile, as verified in Galleria mellonella infection models, highlighted its biocompatibility. RT-qPCR results further indicated that DFP downregulated QS-related gene expression, particularly those involved in ferric uptake regulation protein (Fur). Molecular docking studies identified Fur as a key target for DFP’s inhibitory action. Collectively, DFP was shown as a potential QSI with practical applications for controlling B. cenocepacia infections.
研究领域:
微生物学
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传染病学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
MICROBIAL PATHOGENESIS
·
2022
·
IF 3.848
QiMing Tian,SiMin Wei,HongRui Su,ShuMei Zheng,ShuYa Xu,MingJiang Liu,RuoNan Bo,JinGui Li
The continuous emergence of multidrug-resistant (MDR) bacteria has posed an increasingly serious public health threat which urges people to develop some alternatives. Gallic acid (GA) is a natural ingredient in many traditional Chinese medicines , which has many biological activities, such as antibacterial, and antiseptic. Here, clinical isolates of MDR Escherichia coli ( E. coli ) were used to evaluate the antibacterial effect of GA and the underlying mechanism. The results revealed that GA exerted bactericidal activity and inhibited the formation of bacterial biofilm. GA enhanced the activities of ceftiofur sodium or tetracycline against E. coli , and facilitated antibiotic accumulation in bacteria. Further analysis of morphological alterations and efflux pump gene expressions confirmed that GA damaged outer and inner membranes, and suppressed the mRNA expressions of acrA, acrB, tolC, acrD and acrF involved in membrane permeability . In addition, GA showed protective effects against bacterial infection and improved the survival rates of Galleria mellonella and BALB/c mice. These data highlight a better understanding of GA against bacteria and provide an alternative strategy for MDR bacterial infection.
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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分子生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2024
·
IF 4.4
Li Jie,Xiong Wenguang,Zeng Zhenling
The rapid spread of bacteria with plasmid-mediated resistance to antibiotics poses a serious threat to public health. The search for potential compounds that can increase the antibacterial activity of existing antibiotics is a promising strategy for addressing this issue. Methods: Synergistic activity of the FDA-approved agent oxethazine combined with colistin was investigated in vitro using checkerboard assays and time-kill curves. The synergistic mechanisms of their combination of oxethazine and colistin was explored by fluorescent dye, scanning electron microscopy (SEM) and LC-MS/MS. The synergistic efficacy was evaluated in vivo by the Galleria mellonella and mouse sepsis models. Results: In this study, we found that oxethazine could effectively enhance the antibacterial activity of colistin against both mcr-positive andnegative pathogens, and mechanistic assays revealed that oxethazine could improve the ability of colistin to destruct bacterial outer membrane and cytoplasmic membrane permeability. In addition, their combination triggered the accumulation of reactive oxygen species (ROS), causing additional damage to the membrane structure resulting in cell death. Furthermore, oxethazine significantly enhanced the therapeutic efficacy of colistin in two animal models. Conclusion: These results suggested that oxethazine, as a promising antibiotic adjuvant, can effectively enhance colistin activity, providing a potential strategy for treating multidrug-resistant bacteria.
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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产品关联
DOI
PubMed
高影响因子
CHINESE JOURNAL OF POLYMER SCIENCE
·
2022
·Vol. 41
·期 3
·345-355
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IF 3.815
Liu Hui,Liu Xiao,Cao Yuan-Qiao,Liu Ming,Han Miao-Miao,Ji Sheng-Xiang
Antimicrobial peptides (AMPs) have been considered as an alternative to small molecule antibiotics since they are difficult to develop antimicrobial resistance. Hyperbranched polylysine (HPL), an AMP mimics, has gained attention due to its broad-spectrum antibacterial activities, but it also suffers from high toxicity. Here we report a facile strategy to engineer the toxicity of HPL by copolymerizing lysine (K) with a hydrophobic amino acid, e.g. , alanine (A), tryptophan (W) or phenylalanine (F), to afford hyperbranched random copolymers. These copolymers have comparable antibacterial activities to HPL while their cytotoxicities and in vivo toxicities are lowered when the type and content of hydrophobic amino acid and the size of copolymers are optimized. The G. mellonella infection model demonstrates that the copolymers are effective against the S. aureus infection in vivo . The copolymers kill the bacteria through the disruption of cell membranes and the bacteria do not develop resistance to the copolymers.
研究领域:
材料科学
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生物医学工程
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微生物学
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药学
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产品关联
DOI
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Xin-Rong Wang,Hua Zhong,Shan-Shan Ma,Ya-Hui Huang,Wei-Heng Xu,Yan Wang
Background The incidence of invasive fungal diseases (IFDs), represented by Candida albicans infection, is increasing year by year. However, clinically available antifungal drugs are very limited and encounter challenges such as limited efficacy, drug resistance, high toxicity, and exorbitant cost. Therefore, there is an urgent need for new antifungal drugs. Purpose This study aims to find new antifungal compounds from plants, preferably those with good activity and low toxicity, and reveal their antifungal targets. Methods In vitro antifungal activities of compounds were investigated using broth microdilution method, spot assay, hyphal growth assay and biofilm formation assay. Synergistic effects were assessed using broth microdilution checkerboard technique. In vivo antifungal activities were evaluated using Galleria mellonella and murine candidiasis models. Cytotoxicity of compounds was investigated using Cell Counting Kit-8 (CCK-8). Discovery and validation of antifungal targets of compounds were conducted by using monoallelic knockout library of C. albicans , haploinsufficiency profiling (HIP), thermal shift assay (TSA), enzyme inhibitory effect assay, molecular docking, and in vitro and in vivo antifungal studies. Results 814 plant products were screened, among which petroselinic acid (PeAc) was found as an antifungal molecule. As a rare fatty acid isolated from coriander ( Coriandrum sativum ), carrot ( Daucus carota ) and other plants of the Apiaceae family, PeAc had not previously been found to have antifungal effects. In this study, PeAc was revealed to inhibit the growth of various pathogenic fungi, exhibited synergistic effects with fluconazole (FLC), inhibited the formation of C. albicans hyphae and biofilms, and showed antifungal effects in vivo. PeAc was less toxic to mammalian cells. Fructose-1,6-bisphosphate aldolase (Fba1p) was identified as a target of PeAc by using HIP, TSA, enzyme inhibitory effect assay and molecular docking methods. PeAc exerted antifungal effects more effectively on fba1Δ/FBA1 than wild-type (WT) strain both in vitro and in vivo . Conclusions PeAc is an effective and low toxic antifungal compound. The target of PeAc is Fba1p. Fba1p is a promising target for antifungal drug development.
研究领域:
药理学
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微生物学
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真菌学
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植物化学
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药物发现
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Cellular and Infection Microbiology
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2024
·
IF 4.6
Li Pu,Zhang Sirui,Wang Jingdan,Al-Shamiri Mona Mohamed,Luo Kai,Liu Shuyan,Mi Peng,Wu Xiaokang,Liu Haiping,Tian Huohuan,Han Bei,Lei Jin’e,Han Shaoshan,Han Lei
Introduction: The type VI secretion system (T6SS) is a crucial virulence factor in the nosocomial pathogen Acinetobacter baumannii. However, its association with drug resistance is less well known. Notably, the roles that different T6SS components play in the process of antimicrobial resistance, as well as in virulence, have not been systematically revealed.Methods: The importance of three representative T6SS core genes involved in the drug resistance and virulence of A. baumannii, namely, tssB, tssD (hcp), and tssM was elucidated.Results: A higher ratio of the three core genes was detected in drug-resistant strains than in susceptible strains among our 114 A. baumannii clinical isolates. Upon deletion of tssB in AB795639, increased antimicrobial resistance to cefuroxime and ceftriaxone was observed, alongside reduced resistance to gentamicin. The ΔtssD mutant showed decreased resistance to ciprofloxacin, norfloxacin, ofloxacin, tetracycline, and doxycycline, but increased resistance to tobramycin and streptomycin. The tssM-lacking mutant showed an increased sensitivity to ofloxacin, polymyxin B, and furazolidone. In addition, a significant reduction in biofilm formation was observed only with the ΔtssM mutant. Moreover, the ΔtssM strain, followed by the ΔtssD mutant, showed decreased survival in human serum, with attenuated competition with Escherichia coli and impaired lethality in Galleria mellonella.Discussion: The above results suggest that T6SS plays an important role, participating in the antibiotic resistance of A. baumannii, especially in terms of intrinsic resistance. Meanwhile, tssM and tssD contribute to bacterial virulence to a greater degree, with tssM being associated with greater importance.
研究领域:
微生物学
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传染病学
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抗菌素耐药性
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）