Frontiers in Microbiology
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2023
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IF 5.2
Chen Kai,Qin Ting,Pan Liangkun,Bing Xuwen,Xi Bingwen,Xie Jun
Aeromonas hydrophila is a significant pathogen to freshwater farmed animals, and antibiotics are usually used to control the bacterial septicemia caused by A. hydrophila. Due to the severe situation of development and spread of antibiotic resistance, there are stricter restrictions on antibiotics used in aquaculture. To evaluate the feasibility of glycyrrhetinic acid β (GA) as an alternative therapy against bacterial infection, in this study, an A. hydrophila isolated from diseased fish is used to test the antibacterial, anti-virulence activity and therapeutic effect of GA in vitro and in vivo, respectively. Results showed that GA did not affect the growth of A. hydrophila in vitro, while it could down-regulate (p < 0.05) the mRNA expression of the hemolysis-related genes hly and aerA, and significantly inhibited (p < 0.05) hemolytic activity of A. hydrophila. In addition, in vivo test showed that oral administration of GA was ineffective in controlling acute infections caused by A. hydrophila. In conclusion, these findings suggested that GA was a potential anti-virulence candidate against A. hydrophila, but the application of GA for the prevention and treatment of A. hydrophila-related diseases was still a long way.
研究领域:
微生物学
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水产养殖学
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兽医学
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DOI
PubMed
高影响因子
Current Research in Microbial Sciences
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2025
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IF 5.8
Zhi Wu,Yina Shao,Shanshan Zhang,Chenghua Li
Vibrio splendidus AJ01 is the primary pathogen of Apostichopus japonicus , resulting in huge economic losses. In the present study, we found that 5-iodoindole exhibits a remarkable protective effect on A. japonicus , the survival rate of which can be improved to 93.75%. To explore the impact of 5-iodoindole on V. splendidus AJ01, bacterial growth and virulence factors were determined. Results showed that 5-iodoindole significantly decreased swimming motility, hemolytic activity and protease activity but had minimal effect on the overall growth of the bacterium. Furthermore, a differentially expressed protein was downregulated and identified as elongation factor thermo unstable protein (EF-Tu) via SDS-PAGE combined with LC-MS/MS. Moreover, 5-iodoindole had impact on a large number of genes at RNA level, such as genes related to two-component system, ABC transporters, flagella, and chemotaxis. In addition, 20 µM 5-iodoindole could upregulated the mRNA level of immune related genes in A. japonicus , including IL-17, VEGF and MMP1. Our results indicated 5-iodoindole protect A. japonicus through a two-pronged approach: not only inhibiting bacterial virulence but also enhancing the host's immunity. This not only addresses the limitations of traditional indole but also provides a green alternative to antibiotics for protecting A. japonicus from infections caused by V. splendidus AJ01.
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BIOCHEMICAL PHARMACOLOGY
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2025
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IF 5.6
Chengyu Cai,Shuohui Gao,Bingmei Wang,Tong Zhao,Hang Gao,Yan Shi,Xuerui Guo,Yueshan Xu,Yun Sun,Dongbin Guo,Jinlong Zhang,Fei Gao,Quan Liu,Zeze Fu,Liang Zhu,Xiaolei Liu,Li Wang,Yicheng Zhao
The rising threat of multidrug-resistant (MDR) pathogens, especially methicillin-resistant Staphylococcus aureus (MRSA), necessitates the development of novel antiinfective strategies. Staphylococcus aureus ( S. aureus ), a significant foodborne pathogen, secretes virulence factors that are crucial to its pathogenicity. Unlike conventional antibiotics, antivirulence strategies offer a promising approach by targeting these factors without inhibiting bacterial growth, thereby reducing selective pressure for resistance. Among these factors, von Willebrand factor-binding protein (vWbp) is a key contributor to S. aureus pathogenesis, mediating prothrombin activation and subsequent blood coagulation, which is vital for pathogen survival in the host. This study identified astragaloside IV (As-IV) a bioactive compound from traditional Chinese medicine, as a potent inhibitor of vWbp coagulase. As-IV effectively prolongs coagulation time and reduces S. aureus biotic matrix formation on surfaces relevant to food safety, such as catheters, in vitro . Mechanistic studies, including thermal shift assays (TSAs) and fluorescence quenching, revealed that As-IV directly binds to vWbp, attenuating its activity without altering protein expression levels. In vivo , As-IV exhibited protective effects in infection models, underscoring its potential as a virulence-targeted therapeutic. These findings significantly contribute to the advancement of antivirulence strategies and underscore the potential of As-IV in combating S. aureus infections. This paves the way for its broader application in enhancing public health measures and promoting innovative therapeutic approaches.
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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PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2023
·Vol. 24
·期 18
·14211
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IF 5.6
Jie Li,Ning Han,Yangyang Li,Feifei Zhao,Wenguang Xiong,Zhenling Zeng
Streptococcus suisis an emerging zoonotic pathogen that can cause fatal diseases such as meningitis and sepsis in pigs and human beings. The overuse of antibiotics is leading to an increased level of resistance inS. suis, and novel antimicrobial agents or anti-virulence agents for the treatment of infections caused byS. suisare urgently needed. In the present study, we investigated the antibacterial activity, mode of action and anti-virulence effects of floxuridine againstS. suis. Floxuridine showed excessive antibacterial activity againstS. suisboth in vivo and in vitro; 4 × MIC of floxuridine could killS. suiswithin 8 h in a time–kill assay. Meanwhile, floxuridine disrupted the membrane structure and permeability of the cytoplasmic membrane. Molecular docking revealed that floxuridine and SLY can be directly bind to each other. Moreover, floxuridine effectively inhibited the hemolytic capacity and expression levels of the virulence-related genes ofS. suis. Collectively, these results indicate that the FDA-approved anticancer drug floxuridine is a promising agent and a potential virulence inhibitor againstS. suis.Keywords:floxuridine;Streptococcus suis;mode of action;anti-virulence
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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高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
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2018
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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
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微生物学
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感染病学
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高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2022
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IF 5.195
Wei-Mei Wang,Zhen Zhang,Liang Sun,Chao Ma,Zhi-Hai Liu,Shuai-Cheng Wu
Ethnopharmacological relevance The emergence and spread of antibiotic resistance bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), urgently need to develop alternative strategies or novel antibacterial drugs. Coptis chinensis Franch . , one ancient Chinese herb, has been widely used for the treatment of intestine disease , such as diarrhea. Alkaloids are the major active compounds of Coptis chinensis Franch., and has anti-inflammatory, antioxidant, and antimicrobial effects. Aim of the study The aim of the study was tried to investigate the potential antibacterial effects of the alkaloids from Coptis chinensis Franch. and explore the mechanism. Materials and methods A checkerboard assay, time-killing analysis, membrane functions assay, transcriptome analysis, and inducible resistance test showed the antibacterial effects and mechanisms of alkaloids from Coptis chinensis Franch. Hemolytic assay and MRSA-infected RAW264.7 cells were used to evaluate anti-virulence and anti-inflammatory activities of 13-methylberberine (13-MB). MRSA-infected Vero cells and mouse enteritis models were used to evaluate the anti-infectious effect of 13-MB against MRSA both in vitro and in vivo . Results 13-methylberberine (13-MB) displayed high bactericidal efficiency against methicillin-resistant S. aureus (MRSA). Mechanistic studies showed that 13-MB rapidly killed MRSA by interfering with the proton motive force, ROS generation and membrane fluidity via direct interaction with membrane phospholipids . 13-MB suppressed the virulence of MRSA, modulated the host immune response, and effectively eliminated MRSA in Vero cells. Importantly, 13-MB suppressed weight loss, inflammatory response, bacterial colonization and intestinal lesion in mouse enteritis caused by 13-MB susceptible and resistant S. aureus . Conclusion These results supported the 13-MB has promising potential to be developed as natural drug with antibacterial activity, anti-virulence activity, and host modulation activity for the treatment of enteritis caused by MRSA.
研究领域:
药理学
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微生物学
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免疫学
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民族药理学
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BIOMEDICINE & PHARMACOTHERAPY
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2022
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IF 7.419
Chenchen Wang,Hao Lu,Xiaodan Li,Yongwei Zhu,Yueyue Ji,Wenjia Lu,Gaoyan Wang,Wenqi Dong,Manli Liu,Xiangru Wang,Huanchun Chen,Chen Tan
The persistent incidence of high levels of multidrug-resistant (MDR) bacteria seriously endangers global public health. In response to MDR-associated infections, new antibacterial drugs and strategies are particularly needed. Screening to evaluate a potential compound to reverse antibiotic resistance is a good strategy to alleviate this crisis. In this paper, using high-throughput screening methods, we identified that oxyclozanide potentiated tetracycline antibiotics act against MDR bacterial pathogens by promoting intracellular accumulation of tetracycline in resistant bacteria. Furthermore, mechanistic studies demonstrated that oxyclozanide could directly kill bacteria by disrupting bacterial membrane and inducing the overproduction of bacterial reactive oxygen species. Oxyclozanide effectively reduced the production of virulence proteins in S. aureus and neutralized the produced α-hemolysin, thereby effectively alleviating the inflammatory response caused by bacteria. Finally, oxyclozanide significantly reversed tetracycline resistance in animal infection assays. In summary, these results demonstrated the capacity of oxyclozanide as a novel antibiotic adjuvant, antibacterial and anti-virulence multifunctional compound to circumvent MDR bacteria and improve the therapeutic effect of persistent infections caused by MDR bacteria worldwide.
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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DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2022
·Vol. 11
·期 13
·2200299
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IF 11.092
Jingjing Hu,Sijia Chen,Yongxin Yang,Lin Li,Xuejing Cheng,Yiyun Cheng,Quan Huang
Biofilm is the main culprit of refractory infections and seriously threaten to the human health. Here, a smart hydrogel consisted of norspermidine, aminoglycosides, and oxidized polysaccharide is prepared via the formation of acid-labile imine linkage to treat Pseudomonas aeruginosa biofilm infections in several animal models. The increased acidity caused by bacterial infection triggers the release of norspermidine and aminoglycosides covalently bound with the polymer scaffold. The released norspermidine inhibits biofilm formation and virulence production by regulating the quorum sensing of P. aeruginosa , while the aminoglycoside antibiotics effectively kill the released bacteria. The gel thoroughly inhibits biofilm formation on various medical devices and decreases bacteria pathogenicity. It efficiently inhibits implantation-associated biofilm infections and chronic wound infections, and shows great promise to prevent and treat biofilm-induced refractory infection in clinics.
研究领域:
生物医学工程
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微生物学
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制药学
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传染病学
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PubMed
高影响因子
JOURNAL OF APPLIED MICROBIOLOGY
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2022
·Vol. 133
·期 5
·3161-3175
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IF 4.059
Pan Deng,Wang Xing‐Yun,Zhou Jin‐Wei,Yang Liang,Khan Abbas,Wei Dong‐Qing,Li Jun‐Jian,Jia Ai‐Qun
AimsIn the current study the anti‐virulence and anti‐biofilm activities of the cinnamic acid derivative, 3‐methoxycinnamic acid, was investigated against Agrobacterium tumefaciens.Methods and ResultsBased on the disc diffusion test and β‐galactosidase activity assay, 3‐methoxycinnamic acid was shown to interfere with the quorum sensing (QS) system of A. tumefaciens. Crystal violet staining assay, phenol‐sulfuric acid method, Bradford protein assay and confocal laser scanning microscopy (CLSM) revealed that the biofilm formation of A. tumefaciens was inhibited after the treatment of 3‐methoxycinnamic acid. Employing high‐performance liquid chromatography (HPLC) analysis of culture supernatant revealed that the production of 3‐oxo‐octanoylhomoserine lactone (3‐oxo‐C8‐HSL) decreased concentration‐dependently after treatment with 3‐methoxycinnamic acid. Swimming and chemotaxis assays also indicated that 3‐methoxycinnamic acid had a good effect on reducing the motility and chemotaxis of A. tumefaciens. In addition, the RT‐qPCR, molecular docking and simulations further demonstrated that 3‐methoxycinnamic acid could competitively inhibit the binding of 3‐oxo‐C8‐HSL to TraR and down‐regulate virulence‐related genes.Conclusions3‐Methoxycinnamic acid is proved to have good anti‐virulence and anti‐biofilm activities against A. tumefaciens.Significance and Impact of the StudyThis is the first study that investigates the anti‐virulence and anti‐biofilm activities of 3‐methoxycinnamic acid against A. tumefaciens. With its potential QS‐related virulence and biofilm inhibitory activities, 3‐methoxycinnamic acid is expected to be developed as a potent pesticide or adjuvant for the prevention and treatment of crown gall caused by A. tumefaciens.
研究领域:
微生物学
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植物病理学
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药理学
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DOI
PubMed
高影响因子
Microbiology Spectrum
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2022
·Vol. 10
·期 4
·
IF 9.043
Mohamed Sharaf,Alaa H. Sewid,H. I. Hamouda,Mohamed G. Elharrif,Azza S. El-Demerdash,Afaf Alharthi,Nada Hashim,Anas Abdullah Hamad,Samy Selim,Dalal Hussien M. Alkhalifah,Wael N. Hozzein,Mohnad Abdalla,Taisir Saber
Surface-growing antibiotic-resistant pathogenic bacteria such as Escherichia coli and Staphylococcus aureus are emerging as a global health challenge due to dilemmas in clinical treatment. Furthermore, their pathogenesis, including increasingly serious antimicrobial resistance and biofilm formation, makes them challenging to treat by conventional therapy. Therefore, the development of novel antivirulence strategies will undoubtedly provide a path forward in combatting these resistant bacterial infections. In this regard, we developed novel biosurfactant-coated nanoparticles to combine the antiadhesive/antibiofilm properties of rhamnolipid (RHL)-coated Fe3O4 nanoparticles (NPs) with each of the p-coumaric acid (p-CoA) and gallic acid (GA) antimicrobial drugs by using the most available polymer common coatings (PVA) to expand the range of effective antibacterial drugs, as well as a mechanism for their synergistic effect via a simple method of preparation. Mechanistically, the average size of bare Fe3O4 NPs was ~15 nm, while RHL-coated Fe3O4@PVA@p-CoA/GA was about ~254 nm, with a drop in zeta potential from −18.7 mV to −34.3 mV, which helped increase stability. Our data show that RHL-Fe3O4@PVA@p-CoA/GA biosurfactant NPs can remarkably interfere with bacterial growth and significantly inhibited biofilm formation to more than 50% via downregulating IcaABCD and CsgBAC operons, which are responsible for slime layer formation and curli fimbriae production in S. aureus and E. coli, respectively. The novelty regarding the activity of RHL-Fe3O4@PVA@p-CoA/GA biosurfactant NPs reveals their potential effect as an alternative multitarget antivirulence candidate to minimize infection severity by inhibiting biofilm development. Therefore, they could be used in antibacterial coatings and wound dressings in the future.IMPORTANCE Antimicrobial resistance poses a great threat and challenge to humanity. Therefore, the search for alternative ways to target and eliminate microbes from plant, animal, and marine microorganisms is one of the world’s concerns today. Furthermore, the extraordinary capacity of S. aureus and E. coli to resist standard antibacterial drugs is the dilemma of all currently used remedies. Methicillin-resistant S. aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) have become widespread, leading to no remedies being able to treat these threatening pathogens. The most widely recognized serotypes that cause severe foodborne illness are E. coli O157:H7, O26:H11, and O78:H10, and they display increasing antimicrobial resistance rates. Therefore, there is an urgent need for an effective therapy that has dual action to inhibit biofilm formation and decrease bacterial growth. In this study, the synthesized RHL-Fe3O4@PVA@p-CoA/GA biosurfactant NPs have interesting properties, making them excellent candidates for targeted drug delivery by inhibiting bacterial growth and downregulating biofilm-associated IcaABCD and CsgBAC gene loci.
研究领域:
微生物学
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纳米技术
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药学
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生物医学工程
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DOI
高影响因子
Journal of Materials Chemistry B
·
2024
·
IF 6.1
Hao Li,Yangyang Shi,Hui Chen,Jingou Liang,Shiyong Zhang,Bolei Li,Jing Chen,Mingyun Li,Xian Peng,Xue-Dong Zhou,Biao Ren,Lei Cheng
The scarcity of antifungal drug arsenal highlights an urgent need to develop alternative treatments for candidiasis caused by Candida albicans (C. albicans). As pH is closely associated with C. albicans infection, it could be an essential target in a novel approach for designing antifungal therapy. In this study, a novel intelligent antifungal monomer, Dodecylmethylaminoethyl methacrylate (DMAEM), with a pH-responsive tertiary amine group and a methacrylate-derived C=C double bond group is developed. It is uncovered that the two functional groups of DMAEM contribute to a dual mode of action. Under acidic pH, tertiary amine of DMAEM protonates into a cationic fungicide sharing similar structural and functional characteristics with quaternary ammonium salts, which exerts fungicidal activity by targeting CHK1 two component system in C. albicans. At neutral pH, methacrylate-derived C=C double bond group contributes to anti-virulence activity by blocking hyphal formation. In addition, it is also identified that DMAEM suppresses filamentation by altering C. albicans extracellular vesicles. These findings support the novel intelligent pH-responsive monomer could be a therapeutic candidate for treating candidiasis.
研究领域:
药学
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微生物学
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生物技术
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高影响因子
Frontiers in Pharmacology
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2022
·
IF 5.988
Liu Zhi-Hai,Wang Wei-Mei,Zhang Zhen,Sun Liang,Wu Shuai-Cheng
The emergence and spread of antibiotic-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), underly the urgent need to develop novel antibacterial drugs. Macleaya cordata, a traditional medicinal plant, has been widely used in livestock animals, plants, and humans. Alkaloids are the primary bioactive compounds of Macleaya cordata and exhibit antibacterial, antiinflammatory, and antioxidant activities. Nevertheless, the antibacterial compounds and mode of action of Macleaya cordata remain unclear. In the present study, we investigated the antibacterial activity and mode of action of alkaloids from Macleaya cordata. Sanguinarine, 6-ethoxysanguinarine (6-ES), 6-methoxydihydrosanguinarine (6-MS), chelerythrine (CH), and dihydrochelerythrine (DICH) exhibited good antibacterial activity against Gram-positive bacteria, including MRSA. 6-ES rapidly killed MRSA, possibly by interfering with membrane and metabolic functions including ROS production by targeting the membrane and FtsZ in S. aureus. Additionally, 6-ES directly suppressed the hemolytic activity of α-hemolysin, alleviated inflammatory responses, and eliminated intracellular MRSA, as well as displayed low development of drug resistance, in vitro. Finally, a 6-ES-loaded thermosensitive hydrogel promoted wound healing in mice infected with MRSA. These results supported 6-ES as a novel potential candidate or leading compound with antibacterial, antivirulence, and host immunomodulatory activities in fighting against bacterial infections.
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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植物科学
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DOI
PubMed
高影响因子
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