Antibiotics-Basel
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2022
·Vol. 12
·期 1
·71
·
IF 5.222
Kaiyu Cui,Weifeng Yang,Shuang Liu,Dongying Li,Lu Li,Xing Ren,Yanan Sun,Gaiying He,Shuhua Ma,Jidan Zhang,Qing Wei,Yi Wang
Methicillin-resistantStaphylococcus aureus(MRSA) has posed a severe global health threat. In this study, we screened an antibiotic and non-antibiotic combination that provides a viable strategy to solve this issue by broadening the antimicrobial spectrum. We found that chenodeoxycholic acid (CDCA) could synergistically act with carbapenem antibiotics to eradicate MRSA-related infections. This synergy specifically targets MRSA and was also validated using 25 clinical MRSA strains using time–kill analysis. We speculated that the underlying mechanism was associated with the interaction of penicillin-binding proteins (PBPs). As a result, the synergistic efficiency of CDCA with carbapenems targeting PBP1 was better than that of β-lactams targeting PBPs. Moreover, we showed that CDCA did not affect the expression level of PBPs, but sensitized MRSA to carbapenems by disrupting the cell membrane. In our study, we have revealed a novel synergistic combination of antibiotics and non-antibiotics to combat potential bacterial infections.Keywords:chenodeoxycholic acid;MRSA;carbapenems;penicillin-binding proteins;synergistic inhibition
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
MOLECULAR PHARMACEUTICS
·
2020
·
IF 4.321
Zhe Wang,Xingyun Liu,Ying Peng,Meng Su,Saibin Zhu,Jian Pan,Ben Shen,Yanwen Duan,Yong Huang
Platensimycin (PTM) is a promising natural product drug lead against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), while the clinical development was hampered by problems related to its poor solubility and pharmacokinetic properties. In this study, we used liposomes and micelles as carriers of PTM to prepare PTM nanoformulations for the treatment of MRSA infection in mice. PTM-loaded nanoparticles could effectively reduce residual bacteria in the MRSA-infected macrophage cell model, comparing to free PTM. More importantly, in vivo studies showed that encapsulation of PTM by liposomes or micelles effectively improved the pharmacokinetic properties of PTM in Sprague–Dawley rats and the survival rate of MRSA-infected C57BL/6J mice. Our study has thus suggested that the clinically used nanocarriers, such as liposome and micelle, might also be useful to improve the efficacy of other natural product drug leads to accelerate their in vivo evaluation and preclinical development.
研究领域:
微生物学
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药理学
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纳米医学
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DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2021
·
IF 4.939
Zhe Wang,Xingyun Liu,Yanwen Duan,Yong Huang
Skin and soft tissue infections require effective and sustained topical administration. Platensimycin (PTM) is a natural drug lead that targets bacterial fatty acid synthases and has a great potential to treat infections caused by methicillin-resistant Staphylococcus aureus (MRSA). To facilitate the use of PTM against local MRSA infections, we prepared polyacrylamide hydrogels containing polyamidoamine (PAMAM)/PTM nanoparticles (NP-gel(PTM)) for the controlled release of PTM. NP-gel(PTM) can continuously inhibit the growth of MRSA and its biofilm formation in simulated drug flow models in vitro. In situ implantation of NP-gel(PTM) could treat MRSA-infected subcutaneous soft tissues without toxicity. For MRSA-infected skin wounds, NP-gel(PTM) not only showed strong anti-MRSA activity but also accelerated more wound healing than the widely used antibiotic mupirocin. Collectively, PTM is expected to be used in this safe and effective NP-gel delivery platform for the treatment of local infections, which might help to alleviate the current antibiotic resistance crisis.
研究领域:
药理学
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生物材料
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感染病学
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DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2025
·
IF 4.5
Xiangjun Chen,Xinzhong Zhang,Qing Fan,Menglin Cao,Sai Zhang,Wenting Li,Rui Ma,Xiuping Zhang,Wei Hong
The effective treatment of infections induced by biofilms has remained a substantial challenge in clinical practice. Presently, there is an imperative demand for innovative antimicrobial strategies that can not only eliminate biofilms but also incorporate controlled delivery and intelligent release mechanisms. In this research, the charge-reversible nonantibiotic nanodelivery system (MPDA/AuNCs/ICG@Lip NPs) is synthesized. Initially, AuNCs and indocyanine green (ICG) were introduced onto MPDA NPs via adsorption and mesoporous loading, followed by the modification of the phospholipids on the exterior surface. Within the biofilm microenvironment, the surface charge was reversed, thereby improving its affinity for methicillin-resistant Staphylococcus aureus (MRSA) and facilitating enhanced biofilm permeability. Owing to the ultrasmall AuNCs, they were internalized by the bacteria and, in conjunction with ICG, contributed to the elevation of local ROS concentrations under the 808 nm laser. As anticipated, the in vitro findings confirmed that MPDA/AuNCs/ICG@Lip NPs demonstrated superior biofilm-clearing capabilities and antibacterial effect. In vivo experiments corroborated that MPDA/AuNCs/ICG@Lip NPs successfully targeted the cyst site and remained localized for an extended period, resulting in excellent therapeutic efficacy. This discovery offers a novel perspective for the development of nonantibiotic nanoplatform for clearing MRSA.
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BIOCHEMICAL PHARMACOLOGY
·
2021
·
IF 5.858
Shisong Jing,Li Wang,Tiedong Wang,Lianghai Fan,Lin Chen,Hua Xiang,Yan Shi,Dacheng Wang
Methicillin-resistant Staphylococcus aureus is one of the leading causes of community and nosocomial infections, which has created the urgent need for innovative anti-infective agents to control MRSA-associated infections. A conserved serine protease , caseinolytic peptidase P (ClpP) in Staphylococcus aureus is highly associated with pathogenicity and has been claimed to be a novel antimicrobial target. We aim to search suitable inhibitors of ClpP to attenuate the virulence of MRSA and combat their infections in vivo . Over 500 natural compounds were pre-screened via fluorescence resonance energy transfer using the Suc-LY-AMC substrate. The binding of myricetin to ClpP was determined and the mechanism of action was elucidated by thermal shift assay, surface plasmon resonance , and molecular dynamics simulations. The therapeutic effects of myricetin on S. aureus infection were further investigated using a S. aureus -induced pneumonia model. We revealed that myricetin could effectively block the activity of ClpP without disturbing the growth of the bacteria and the Gln-47 and Met-31 residues were necessary for myricetin binding to ClpP. Importantly, myricetin attenuated the pathogenicity of S. aureus in vivo , while improving the efficacy of the traditional antibiotic oxacillin against MRSA infection and protecting mice from fatal lung infections caused by MRSA. These findings indicate that myricetin has the potential to be applied in the pharmaceutical industry as a promising therapeutic agent.
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
JOURNAL OF ETHNOPHARMACOLOGY
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2022
·
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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PubMed
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BIOMACROMOLECULES
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2025
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IF 5.4
Yujia Lu,Guanyi Li,Yanwen Zhang,Yuxuan Ge,Bin Hao,Yu Yin,Yaxue Zhao,Yin Wang
Antimicrobial peptides (AMPs) are a class of peptides consisting of cationic amino acid residues and a hydrophobic segment, which have been used as an alternative to antibiotics in treating multidrug-resistant bacteria. However, the relationship among the molecular design, assembled structures, and resultant efficacy remains elusive. Herein, we report a class of constitutionally isomeric AMPs assembled into filaments with similar dimensions. Spectroscopic characterizations demonstrated that subtle changes in the position of amino acids led to dramatic variations in molecular packing and surface charges, which were verified by molecular dynamics simulations. In vitro antibacterial assays showed that all AMPs exerted antibacterial activity against Gram-positive methicillin-resistant Staphylococcus aureus (MRSA), but the efficacy was dependent on the molecular design. Given the good biocompatibility to eukaryotic cells, these AMPs could be potentially used as antibacterial agents. We believe that this finding provides an avenue to tune the bioactivity of AMPs by rational molecular design.
研究领域:
生物化学
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微生物学
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PubMed
高影响因子
Chemical Biology & Drug Design
·
2024
·Vol. 103
·期 6
·e14554
·
IF 3.2
Hui-xian Liu,Wen-yu Yao,Ge Cui,Jing Zhou,Hao Yan,Hui Guo,Yu-wei Wang,Yue Zhang
This paper reports the design, synthesis, and antibacterial activity study of pleuromutilin derivatives with 2-methyl-4-nitroaniline and 2-methoxy-4-nitroaniline side chains at the C22 position. The structures of the new compounds were characterized by 1 H-NMR, 13 C-NMR and HRMS. The inhibitory activity of the compounds against MSSA, pyogeniccoccus , streptococcus , and MRSA strains was determined using the micro broth dilution method. The results showed that the compounds exhibited certain activity against Gram-positive bacteria, among which compounds A8a, A8b, A8c, A8d, and A7 demonstrated superior antibacterial activity against MSSA, MRSA, and pyogeniccoccus compared to tiamulin, although the derivatives showed lower antibacterial activity against streptococcus compared to the control drug. Based on the favorable in vitro activity of A8c, the time-kill kinetics against MRSA were evaluated, revealing that compound A8c could inhibit bacterial proliferation in a concentration-dependent manner.
研究领域:
药理学
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有机化学
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微生物学
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PubMed
高影响因子
Microbial Drug Resistance
·
2020
·Vol. 26
·期 2
·100-109
·
IF 2.519
Chong-Fa Lai,Wei-Bin Xiao,Hua-Cheng Yan,Hui Yang,Lu-Xia Wang,Hui Guan,Qiu-ju Peng,Zhi-Rong Deng,Jian-Wen Chen,Lin-Kun An,Lei Shi
ZTW-41, an indolizinoquinoline-5,12-dione derivative, was investigated for antibacterial activity against Gram-positive bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA). In our study, the MIC90s (minimum inhibitory concentrations) of ZTW-41 against MRSA (MRSA, n = 200), methicillin-sensitive S. aureus (MSSA, n = 100), Enterococcus faecalis (E. faecalis, n = 32), and Enterococcus faecium (E. faecium n = 32) were 0.25, 0.25, 0.125, and 8 μg/mL, respectively, whereas the MBC90s (minimum bactericidal concentrations) were 2, 1, 1, and >32 μg/mL, respectively. ZTW-41 maintained its potency at different pH levels (range 5–9) and in starting inoculum size up to 107 CFU/mL. The presence of human serum (25–75%) increased ZTW-41 MICs by two- to eightfold. Time-kill curves showed that ZTW-41 had bactericidal activity against MRSA, MSSA, and E. faecalis strains within 8 hours, and rebound growth occurred after 8 hours except at higher multiples of the MIC (4 × and 8 × ). In the acute toxicity study, no mortality or signs of toxicity was noted in mice after 14 days of observation at doses <50 mg/kg. ZTW-41 exhibited good selectivity indices (SIs) (SI = IC50/MIC90) ranging from 1.12 to 71.76 against clinical isolates, demonstrating excellent therapeutic selectivity in MRSA, MSSA, and E. faecalis strains. Moreover, the in vivo efficacy (effective dose [ED]50 = 6.59 mg/kg) of ZTW-41 was found comparable with vancomycin. Collectively, our favorable results supported ZTW-41 as a promising investigational candidate for treating drug-resistant bacteria infection.
研究领域:
微生物学
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药理学
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感染病学
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PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2026
·
IF 5.9
Xiang Che,Zena Chen,Qian Shen,Zhongxi Huang,Yao Wang,Yangyang Pu,Jiarui Shi,Zhipeng Zhang,Naidi Yang,Changmin Yu
A green strategy constructs quaternary ammonium‑functionalized, resveratrol‑loaded polydopamine nanoparticles (R@P)G . • (R@P)G exhibits antibacterial activities against MRSA by disrupting membrane integrity and inducing intracellular leakage. • The nanoplatform enables efficient ROS scavenging and protects cells against oxidative stress under inflammatory conditions. • (R@P)G suppresses pro-inflammatory cytokine, remodels the immune microenvironment and promotes MRSA-infected wound healing. • This multifunctional nanoplatform provides a biosafe and clinically translatable strategy for treating MRSA-infected wounds. Drug-resistant bacterial infection, oxidative stress, and persistent inflammation collectively hinder chronic wound healing, yet most antibacterial nanomaterials fail to address these interconnected pathological factors. Herein, we report a simple and green nanoplatform based on surface-quaternized, resveratrol-loaded polydopamine nanoparticles (denoted (R@P)G ) for the treatment of methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds. Surface quaternization introduces cationic motifs that enable effective bacterial membrane disruption, achieving highly efficient killing of MRSA and effective biofilm eradication. Meanwhile, the polydopamine–resveratrol redox system provides broad-spectrum reactive oxygen species scavenging, alleviating oxidative damage and restoring fibroblast function. In addition, (R@P)G significantly accelerates wound closure, enhances collagen deposition and re-epithelialization, and suppresses inflammatory cytokines in vivo . The solvent-free synthesis and favorable biosafety further support its translational potential. This work presents a multifunctional biomaterial strategy for coordinated antibacterial and microenvironmental regulation in infected wound repair, offering a promising approach for the treatment of drug-resistant wound infections.
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DOI
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Shouli Yi,Hongjuan Zhang,Zhen Yang,Di Wu,Dan Shao,Jiongjie He,Yu Liu,Baocheng Hao,Shengyi Wang
Methicillin-resistant Staphylococcus aureus (MRSA) infections and the formation of associated biofilms often lead to refractory and recurrent bacterial infections, posing a serious threat to public health. Herein, a pH-responsive antibiotic-free nanoparticle (HNK@RHL-COS NPs) was prepared by encapsulating the natural antimicrobial agent honokiol (HNK) with rhamnolipid-modified chitosan, enabling targeted disassembling at the acidic infection site, destruction of the biofilm by rhamnolipid, thereby enhancing the penetration of honokiol and chitosan, thus achieving their synergistic bactericidal effect. HNK@RHL-COS NPs exhibited enhanced antimicrobial effects against MRSA, with a minimum inhibitory concentration (MIC) value of 2 μg/mL, significantly inhibited the formation of biofilm and eradicated the mature biofilm. Furthermore, HNK@RHL-COS NPs efficiently accelerated the healing of wounds in MRSA-infected mice, alleviated bacterial peritonitis in mice, and demonstrated excellent biocompatibility in vitro and in vivo . Collectively, this study provides a novel and safety solution for the clinical treatment of MRSA infections.
研究领域:
纳米医学
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抗菌治疗
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生物医学工程
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传染病
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药物递送
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DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Jingchen Xu,Yao Lin,Yue Wang,Hongyu Gao,Yuanhong Li,Chaoliang Zhang,Qianming Chen,Song Chen,Qiang Peng
Repeated microbial infection, excess reactive oxygen species (ROS) accumulation, cell dysfunction, and impaired angiogenesis under hyperglycemia severely inhibit diabetic wound healing. Therefore, developing multifunctional wound dressings accommodating the complex microenvironment of diabetic wounds is of great significance. Here, a multifunctional hydrogel (Regesi-CS) is prepared by loading regeneration silicon (Regesi) in the non-crosslinked chitosan (CS) solution, followed with freeze-drying and hydration. As expected, the blank non-crosslinked CS hydrogel (1%) shows great antibacterial activity against E. coli , S. aureus , and MRSA, improves fibroblasts migration, and scavenges intracellular ROS. Interestingly, after loading 1% Regesi, the Regesi-CS (1%-1%) hydrogel shows greater antibacterial activity, significantly promotes fibroblasts proliferation and migration, scavenges much more ROS, and substantially protects fibroblasts under oxidative stress, yet Regesi alone has no or even negative effects. In the MRSA-infected diabetic wound model, Regesi-CS (1%-1%) hydrogel effectively promotes wound healing via eliminating bacterial infection, enhancing granulation tissue formation, promoting collagen deposition, and improving angiogenesis. In conclusion, Regesi-CS hydrogel may be a potential wound dressing for effective treatment and management of chronic diabetic wounds. This article is protected by copyright. All rights reserved
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