JOURNAL OF ANTIBIOTICS
·
2025
·
IF 2.7
Jiang Hanxiang,Qi Jiangfeng,Wang Jiwen,Chen Jiaqin,Feng Dong,Yang Junbiao,Liu Xinna,Liu Mengqun,Zhou Xvzhe,An Zhilong,Lu Yuanyuan,Ge Chun,Wang Ying
Acetobacter baumannii poses escalating clinical challenges due to its exceptional adaptability, demanding innovative antimicrobial strategies. This study pioneers an investigation into the antibacterial efficacy and molecular mechanism of Terramide A, a hydroxamate siderophore isolated from Aspergillus terreus, against notorious A. baumannii . Employing a multidisciplinary approach integrating phenotypic characterization with mechanistic interrogation, we demonstrate that Terramide A exerts significant inhibitory effects against A. baumannii and P. aeruginosa , pathogens critically dependent on siderophore-mediated iron acquisition for survival and virulence. Structural characterization underlines the hydroxamate moieties of Terramide A presumably supports its hypothesized role as a fungal siderophore, involving competitive iron sequestration and bacterial homeostasis. Subsequently, multi-omics investigation of susceptible strain AB19606 delineated a metabolic collapse cascade due to iron acquisition competition: (1) impairment of central metabolism and energy production through oxidative phosphorylation (OXPHO) inhibitions; (2) compromised stress adaptation and bacterial flexibility; (3) compensatory overactivation of siderophores biosynthesis and transportation, depleting metabolic intermediates and exacerbating stress; (4) coordinated suppression of virulence determinants, such as secretory systems and biofilm formation. These molecular derangements translated into phenotypic deficits, including quorum sensing, diminished autoinducer peptides production, and morphological/functional abnormalities. In vivo evaluation in a rat skin wound infection model further demonstrated that Terramide A promotes wound healing and mitigates inflammation, supporting its antibacterial efficacy. These findings establish Terramide A as a promising antibacterial agent and provide critical insights into iron-competitive antimicrobial strategies to exploit micro-nutrient deprivation and metabolic dysfunction. However, further research is needed to optimize the siderophore-based scaffold, clarify its mechanisms, and assess therapeutic potential.
研究领域:
微生物学
·
药理学
·
感染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
·
2018
·Vol. 103
·期 2
·903-915
·
IF 3.34
Wang Hong,Chu Weihua,Ye Chao,Gaeta Bruno,Tao Huimin,Wang Min,Qiu Zheng
Quorum sensing (QS) is a cell-to-cell communication that is used by bacteria to regulate collective behaviors. Quorum sensing controls virulence factor production in many bacterial species and it is regarded as an attractive target to combat bacterial pathogenicity, especially against antibiotic-resistant bacteria. Chlorogenic acid (CA), abundant in fruits, vegetables, and Chinese herbs, processes multiple activities. In this research, we explored its quorum sensing quenching activity. In Pseudomonas aeruginosa , CA significantly inhibited the formation of biofilm, the ability of swarming, and virulence factors including protease and elastase activities and rhamnolipid and pyocyanin production. CA showed similar inhibitory effects in Chromobacterium violaceum on its biofilm formation, swarming motility, chitinolytic activity and violacein production. We examined the expression of QS-related genes in P.aeruginosa and found these genes were all downregulated by CA treatment. Computational modeling revealed that CA can form hydrogen bonds with all three QS receptors. Caenorhabditis elegans and mouse infection models were employed to explore the anti-virulence ability of CA and its effect on pathogenesis process in vivo . CA extended the survival period and reduced the quantity of P. aeruginosa in nematode gut, showing a moderate protective effect on C. elegans . In mice wound model, CA-treated groups showed an accelerating healing rate and the bacteria number in wound area was also decreased by CA treatment. It is suggested by our research that CA has potential to be used as an anti-virulence factor in P. aeruginosa infection.
研究领域:
微生物学
·
药理学
·
感染病学
✓ 已验证
DOI
PubMed
高影响因子
Biofilm
·
2024
·
IF 5.9
Shi-Liang Xiang,Kai-Zhong Xu,Lu-Jun Yin,Yong Rao,Bo Wang,Ai-Qun Jia
Pseudomonas aeruginosa is recognized globally as an opportunistic pathogen of considerable concern due to its high virulence and pathogenicity, especially in immunocompromised individuals. While research has identified several endogenous quorum sensing (QS) signaling molecules that enhance the virulence and pathogenicity of P. aeruginosa , investigations on exogenous QS signaling molecules or modulating factors remain limited. This study found that dopamine serves as an exogenous QS signaling molecule or modulating factor of P. aeruginosa PAO1, enhancing the production of virulence factors and biofilms. Compared to the control group, treatment with 40 μM dopamine resulted in a 33.1 % increase in biofilm formation, 68.1 % increase in swimming mobility, 63.1 % increase in swarming mobility, 147.2 % increase in the signaling molecule 3-oxo-C12-HSL, and 50.5 %, 28.5 %, 27.0 %, and 33.2 % increases in the virulence factors alginate, rhamnolipids, protease, and pyocyanin, respectively. This study further explored the mechanism of dopamine regulating the biofilm formation and virulence of P. aeruginosa PAO1 through transcriptome and metabolome. Transcriptomic analysis showed that dopamine promoted the expression of virulence genes psl, alg, lasA, rhlABC , rml , and phz in P. aeruginosa PAO1. Metabolomic analysis revealed changes in the concentrations of tryptophan, pyruvate, ethanolamine, glycine, 3-hydroxybutyric acid, and alizarin. Furthermore, KEGG enrichment analysis of altered genes and metabolites indicated that dopamine enhanced phenylalanine, tyrosine, and tryptophan in P. aeruginosa PAO1. The results of this study will contribute to the development of novel exogenous QS signaling molecules or modulating factors and advance our understanding of the interactions between P. aeruginosa and the host environment.
研究领域:
微生物学
·
分子生物学
·
感染与免疫
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Microbiology
·
2023
·
IF 5.2
Li Wen-Ru,Zeng Tao-Hua,Zhang Zhi-Qing,Shi Qing-Shan,Xie Xiao-Bao
Pseudomonas aeruginosa is a ubiquitous opportunistic pathogen that can cause severe respiratory tract infections. Geraniol, a chemical component of essential oils, has antimicrobial and anti-inflammatory activities, along with low toxicity. However, the effect and mechanism of geraniol against P. aeruginosa virulence factors are rarely studied. In this study, we investigated the quorum sensing (QS) inhibitory effects and mechanisms of geraniol against P. aeruginosa PAO1, using physiological and biochemical techniques, quantitative reverse transcription polymerase chain reaction, and transcriptomics. Geraniol slightly affected P. aeruginosa PAO1 growth, prolonged the lag phase, and delayed growth periods in a concentration-dependent manner. Geraniol inhibited three QS systems of P. aeruginosa, las, rhl, and pqs by suppressing the expression level of their key genes, including the three signal synthetase encoding genes of lasI, rhlI, and pqsABCDEH, and the corresponding signal receptor encoding genes of lasR, rhlR, and pqsR. Geraniol also suppressed certain virulence genes regulated by these three QS systems, including rhlABC, lasAB, lecAB, phzABMS, and pelABG, resulting in the attenuation of the related virulence factors, rhamnolipids, exoprotease LasA, elastase, lectin, pyocyanin, and biofilm. In conclusion, geraniol can suppress the virulence factors of P. aeruginosa PAO1 by inhibiting the three QS systems of las, rhl, and pqs. This study is significant for improving the treatment of bacterial infections caused by P. aeruginosa.
研究领域:
微生物学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ARCHIVES OF ORAL BIOLOGY
·
2019
·
IF 1.663
Qiaomu Huang,Shilei Wang,Yujun Sun,Cheng Shi,Hao Yang,Zhong Lu
Objective Streptococcus mutans ( S. mutans ), the main pathogen of dental caries, could be well killed by Ag/ZnO nanocomposite. However, effects on virulence factors remain to be elucidated. This study investigated effects of Ag/ZnO at sub-minimum inhibitory concentrations (sub-MICs) on virulence factors of S. mutans and related genes expressions. Design Effects of Ag/ZnO on the growth of S. mutans was investigated by growth curves and MTT staining method. The influence of Ag/ZnO at sub-MICs on biofilm formation was measured by the crystal violet staining method and observed by a scanning electron microscopy. Adherence, cell-surface hydrophobicity, acidogenicity and extracellular polysaccharides (EPS) of S. mutans after treatment by Ag/ZnO at sub-MICs were also investigated. Virulence factors related genes expressions after treated by Ag/ZnO at 1/2 MIC was conducted by the quantitative real-time PCR (qRT-PCR) method. Results Sub-MICs of Ag/ZnO exhibited a dose-dependent inhibition on the virulence factors of S. mutans . Specially, Ag/ZnO at 1/2 MIC decreased 69.00 % biofilm formation, 31.78 % sucrose-independent and 48.08 % sucrose-dependent adherence, 69.44 % cell-surface hydrophobicity and 72.45 % water-soluble and 90.60 % water-insoluble EPS. Furthermore, the expression of virulence factors related genes was significantly suppressed by Ag/ZnO at 1/2 MIC. Conclusions Ag/ZnO at sub-MICs inhibited multiple virulence factors of S. mutans through downregulating the related genes. Ag/ZnO nanocomposite could be used for prevention of dental caries at low dosage.
研究领域:
口腔微生物学
·
纳米医学
·
分子生物学
✓ 已验证
DOI
高影响因子
Food Bioscience
·
2025
·
IF 5.9
Peiyun Li,Xiaochen Chen,Tariq Aziz,Ashwag Shami,Fahad Al-Asmari,Fakhria A. Al-Joufi,Haiying Cui
The virulence factors including biofilm and virulence proteins in Listeria monocytogenes ( L. monocytogenes ) threatens human health. Herein, the inhibitory mechanisms of carvacrol (CAR) on the biofilm formation and virulence production in L. monocytogenes were explored. It was found the minimum biofilm inhibition concentration of CAR was 0.8 mg/mL. CAR could effectively inhibit bacterial biofilm formation by reduction of extracellular polymeric substance, including extracellular polysaccharides, proteins, and DNA. CAR could interfere with the bacterial swarming and swimming motilities, thereby hindering biofilm development. Hemolytic capability of Listeriolysin O was significantly decreased from 85.75 % to 28.13 % after treatment with CAR at the minimum inhibitory concentration (MIC). Transcriptomic analysis revealed exposure to 1/2 MIC of CAR resulted in 969 differentially expressed genes, with downregulation of virulence factor-related genes. CAR might bind to AgrB within the quorum sensing system, thereby affecting the biofilm formation regulation and virulence expression. In addition, CAR exhibited efficient inhibitory effects on the biofilm formation on different food contacting materials and vegetable surfaces. These findings provided new insights into biofilm-inhibition and virulence-reduction mechanisms of CAR on L. monocytogenes, suggesting potential applications in controlling L. monocytogenes biofilm contamination in food industries.
研究领域:
微生物学
·
食品安全
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
PARASITOLOGY RESEARCH
·
2023
·Vol. 123
·期 1
·1-6
·
IF 2
Wang Bingxiang,Zhao Ningning,Sun Lingyu,Tan Qianqian,Xiao Qianqian,Chen Junpeng,Li Jinxuan,Zhang Xiao,Zhao Xiaomin
Difficulties of in vitro culture and genetic manipulation of Eimeria tenella have hindered the screening of virulence factors in this parasite. In this study, the E. tenella rhoptry protein 30 (EtROP30) was expressed in Toxoplasma gondii (RH∆Ku80-EtROP30), and its effect on the proliferation and virulence of parasites was investigated. The results revealed that the expression of EtROP30 had no impact on the invasion and egress processes. However, the RH∆Ku80-EtROP30 strain formed larger plaques compared to the RH∆Ku80, indicating that the EtROP30 expression promotes T. gondii proliferation. Furthermore, the RH∆Ku80-EtROP30 strain exhibited greater pathogenicity, resulting in earlier mortality and shorter overall survival time compared to RH∆Ku80. These results imply that EtROP30 expression facilitates parasite intracellular proliferation and virulence in mice, suggesting that EtROP30 might be a candidate virulence factor of E. tenella.
研究领域:
寄生虫学
·
分子生物学
·
传染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LWT-FOOD SCIENCE AND TECHNOLOGY
·
2024
·
IF 6
Zitong Ge,Xiaxin Du,Jianan Liu,Junya Zhu,Hongshun Hao,Jingran Bi,Hongman Hou,Gongliang Zhang
Pseudomonas fluorescens , a specific spoilage organism, can control cell density and various physiological processes through quorum sensing (QS). Quorum sensing inhibitors (QSIs) are a crucial strategy for enhancing food quality and safety. In this study, benzyl isothiocyanate (BITC) at subminimum inhibitory concentrations (MICs) promoted protein and nucleic acid leakage, β-galactosidase activity and the relative fluorescence intensity of the membrane potential in P. fluorescens . N-butyryl- l -homoserine lactone (C4-HSL) and N-decanoyl- l -homoserine lactone (C10-HSL) were detected in P. fluorescens by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). C4-HSL and C10-HSL are known to orchestrate the QS of gram-negative bacteria. The inhibition rates of C4-HSL and C10-HSL by BITC at 1/2 MIC were 54.0%–96.2% and 31.6%–70.5%, respectively, after cultured with P. fluorescens for 6–24 h. The inhibitory effects of BITC at 1/4 MIC on P. fluorescens biofilm formation, extracellular polysaccharide production, and motility were enhanced in the presence of exogenous C4-HSL. Moreover, sub-MICs of BITC markedly downregulated the relative expression of QS-related genes , and the molecular docking results also showed excellent binding ability of BITC to QS proteins. This study demonstrated the feasibility of BITC as a QSI, whereby exogenous C4-HSL promoted the ability of BITC to disturb the QS system in P. fluorescens .
研究领域:
微生物学
·
食品安全
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2018
·
IF 3.466
Qi Liu,Wei-Wei Ni,Zhen Li,Cai-Fu Bai,Dan-Dan Tan,Chang-Jun Pu,Dong Zhou,Qing-Peng Tian,Ni Luo,Kai-Li Tan,Le Dai,Yuan Yan,Yong Pei,Xian-Hui Li,Zhu-Ping Xiao,Hai-Liang Zhu
The continuing emergence of drug-resistant Helicobacter pylori (HP) drives the ongoing need for the development of new and effective anti-HP drugs. Urease inhibitor has now gained strong interest as an alternative approach for HP infections . 3-Chlorophenyl-3-hydroxypropionylhydroxamic acid (CPH), a novel urease inhibitor identified in our group, shows impressive potency, which was optically separated for a further exploration. Here, we report in vitro / in vivo pharmacological evaluation of (±)-CPHs and the enantiomers. The raceme and the individual enantiomers significantly suppress gastritis at 32 mg/kg b.i.d dose with lower toxicity to mammalian cells (with CC 50 s ≥ 3.16 mM) and mice (LD 50 s ≥ 2338 mg/kg) than the clinically used agent acetohydroxamic acid . Furthermore, a significant increase of eradication of HP is observed for the combination of (±)-CPHs or the enantiomers with an antimicrobial. These studies revealed that CPH is a promising candidate for an alternative treatment of HP-dependent conditions by targeting virulence factor urease, and CPH may be used as a raceme.
研究领域:
药理学
·
微生物学
·
感染病学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Molecular Biosciences
·
2022
·
IF 6.113
Li Tinghan,Wen Yibo,Guo Hangtian,Yang Tingting,Yang Haitao,Ji Xiaoyun
The accessory protein Orf6 is uniquely expressed in sarbecoviruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is an ongoing pandemic. SARS-CoV-2 Orf6 antagonizes host interferon signaling by inhibition of mRNA nuclear export through its interactions with the ribonucleic acid export 1 (Rae1)–nucleoporin 98 (Nup98) complex. Here, we confirmed the direct tight binding of Orf6 to the Rae1-Nup98 complex, which competitively inhibits RNA binding. We determined the crystal structures of both SARS-CoV-2 and SARS-CoV-1 Orf6 C-termini in complex with the Rae1–Nup98 heterodimer. In each structure, SARS-CoV Orf6 occupies the same potential mRNA-binding groove of the Rae1–Nup98 complex, comparable to the previously reported structures of other viral proteins complexed with Rae1-Nup98, indicating that the Rae1–Nup98 complex is a common target for different viruses to impair the nuclear export pathway. Structural analysis and biochemical studies highlight the critical role of the highly conserved methionine (M58) of SARS-CoVs Orf6. Altogether our data unravel a mechanistic understanding of SARS-CoVs Orf6 targeting the mRNA-binding site of the Rae1–Nup98 complex to compete with the nuclear export of host mRNA, which further emphasizes that Orf6 is a critical virulence factor of SARS-CoVs.
研究领域:
病毒学
·
分子生物学
·
结构生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULES
·
2024
·Vol. 29
·期 10
·2354
·
IF 4.2
Jia-Le Zhou,Hao-Han Chen,Jian Xu,Ming-Yu Huang,Jun-Feng Wang,Hao-Jie Shen,Sheng-Xiang Shen,Cheng-Xian Gao,Chao-Dong Qian
Background:Staphylococcus aureusis a common pathogenic microorganism in humans and animals. Type II NADH oxidoreductase (NDH-2) is the only NADH:quinone oxidoreductase present in this organism and represents a promising target for the development of anti-staphylococcal drugs. Recently, myricetin, a natural flavonoid from vegetables and fruits, was found to be a potential inhibitor of NDH-2 ofS. aureus. The objective of this study was to evaluate the inhibitory properties of myricetin against NDH-2 and its impact on the growth and expression of virulence factors inS. aureus. Results: A screening method was established to identify effective inhibitors of NDH-2, based on heterologously expressedS. aureusNDH-2. Myricetin was found to be an effective inhibitor of NDH-2 with a half maximal inhibitory concentration (IC50) of 2 μM. In silico predictions and enzyme inhibition kinetics further characterized myricetin as a competitive inhibitor of NDH-2 with respect to the substrate menadione (MK). The minimum inhibitory concentrations (MICs) of myricetin againstS. aureusstrains ranged from 64 to 128 μg/mL. Time–kill assays showed that myricetin was a bactericidal agent againstS. aureus. In line with being a competitive inhibitor of the NDH-2 substrate MK, the anti-staphylococcal activity of myricetin was antagonized by MK-4. In addition, myricetin was found to inhibit the gene expression of enterotoxin SeA and reduce the hemolytic activity induced byS. aureusculture on rabbit erythrocytes in a dose-dependent manner. Conclusions: Myricetin was newly discovered to be a competitive inhibitor ofS. aureusNDH-2 in relation to the substrate MK. This discovery offers a fresh perspective on the anti-staphylococcal activity of myricetin.
研究领域:
微生物学
·
药理学
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Quan Chen,Yue Zhang,Wan-Rong Zhang,Yu Huang,Min Wu,Hong-Zhe Li,Yi-Yue Zhang,Yi-Fei Wang,Dong Zhu,Philippe Frangois-Xavier Corvini,Bo Pan
Engineered environmental particles are introduced, generated, or released during engineering activities, significantly accumulating after entering the soil ecosystem. When these particles adsorb pollutants, they inevitably interact with soil microorganisms, potentially altering soil microbial ecosystem function. This study evaluated the variation of ecological risks before and after pollutant (organic tetracycline and inorganic Cd) adsorption of three commonly detected engineered environmental particles and one natural soil particle on soil microorganisms. Absorbance measurements of soil bacterial suspensions indicated that pollutant-adsorbed particles significantly inhibited soil bacterial growth compared to raw particles. These composite particles triggered bacterial stress responses and activated bacterial self-protective mechanisms through enhanced extracellular polymeric substance (EPS) production, with protein and polysaccharide concentration ranges increased from 163.12-243.10 mg/L and 75.25–87.23 mg/L to 232.84–294.10 mg/L and 74.29–93.96 mg/L, respectively. Soil bacteria exhibited consistent biofilm formation and robust stress responses when exposed to nanoparticles (either alone or pollutant-complexed). These responses created extracellular barriers that mitigated harmful substance penetration while maintaining cellular integrity and viability, reducing LDH concentration range from 173.55 to 300.92 U/CFU to 88.26–154.45 U/CFU. 16S rRNA sequencing exposed phylum-level community shifts under particle stress: Firmicutes abundance decreased 11–13 %, inversely correlating with Proteobacteria increases. The pollutant adsorption significantly increased the selective enrichment of ARGs and virulence factor genes (VFGs), suggesting an enhanced survival advantage for pathogenic microbes and accelerated dissemination of resistance determinants. This study reveals the mechanisms determining the ecological risk of engineered environmental particles during the pollutant adsorption and benefits the development of new environmental risk assessment frameworks.
研究领域:
环境科学
·
微生物学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）