Materials Today Communications
·
2022
·
IF 3.662
Deyan Gong,Xiang Huang,Zineng Yi,Qianpeng Zhou,Xiaona Xu,Xiaohan Meng,Congyu Liu,Zhaohua Miao,Zhengbao Zha
As a metabolite or reductive cytoprotective gas of bacteria to mediate and mitigate the oxidative stress imposed by antibiotics, hydrogen sulfide (H 2 S) related drug-resistant mechanisms represent a growing point in bacteria drug-resistant research. Thereby, novel diagnostic strategies exploration for H 2 S related drug-resistant pathways recognition are important for drug-resistant bacteria monitoring. Herein, a new organic fluorescent dye ( E )− 3-(3,3-dimethyl-2-styryl-3 H -benzo[ f ]indol-1-ium-1-yl) propane-1-sulfonate self-assembled nanoprobe (DPS NP, ~200 nm) was designed for ratiometric fluorescent monitoring the change of H 2 S concentration. DPS NP exhibited ratiometric fluorescence alteration from yellow (λ em = 553 nm) to blue (λ em = 464 nm) due to nucleophilic addition reaction with H 2 S within five minutes. DPS NP exhibits remarkable capabilities with selectively sensitive colorimetric and ratiometric fluorescent alteration toward H 2 S over other analytes. Fluorescence microscopy imaging or ratiometric fluorescent visualization for monitoring the concentration of bacterial released H 2 S show DPS NP can act as particular diagnostic technique for screening of β -lactam antibiotic resistance in Methicillin-resistant Staphylococcus aureus (MRSA) and nonresistant bacteria Staphylococcus aureus ( S. aureus ) .
研究领域:
微生物学
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医学诊断
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化学传感
✓ 已验证
DOI
高影响因子
Antibiotics-Basel
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2024
·Vol. 13
·期 3
·278
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IF 4.3
Chun Wang,Yun-Yao Ren,Li-Mei Han,Peng-Cheng Yi,Wei-Xiao Wang,Cai-Yun Zhang,Xiu-Zhen Chen,Ming-Zhe Chi,Apeng Wang,Wei Chen,Chun-Mei Hu
Antimicrobial peptides (AMPs) hold promise as alternatives to combat bacterial infections, addressing the urgent global threat of antibiotic resistance. COG1410, a synthetic peptide derived from apolipoprotein E, has exhibited potent antimicrobial properties against various bacterial strains, includingMycobacterium smegmatis. However, our study reveals a previously unknown resistance mechanism developed byM. smegmatisagainst COG1410 involving ClpC. Upon subjectingM. smegmatisto serial passages in the presence of sub-MIC COG1410, resistance emerged. The comparative genomic analysis identified a point mutation in ClpC (S437P), situated within its middle domain, which led to high resistance to COG1410 without compromising bacterial fitness. Complementation of ClpC in mutant restored bacterial sensitivity. In-depth analyses, including transcriptomic profiling and in vitro assays, uncovered that COG1410 interferes with ClpC at both transcriptional and functional levels. COG1410 not only stimulated the ATPase activity of ClpC but also enhanced the proteolytic activity of Clp protease. SPR analysis confirmed that COG1410 directly binds with ClpC. Surprisingly, the identified S437P mutation did not impact their binding affinity. This study sheds light on a unique resistance mechanism against AMPs in mycobacteria, highlighting the pivotal role of ClpC in this process. Unraveling the interplay between COG1410 and ClpC enriches our understanding of AMP-bacterial interactions, offering potential insights for developing innovative strategies to combat antibiotic resistance.
研究领域:
微生物学
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药理学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Global Antimicrobial Resistance
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2016
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IF 1.087
Dongmei Wu,Ruochen Lu,Yuquan Chen,Jie Qiu,Chaocheng Deng,Qiang Tan
This study aimed to determine whether selection by antibiotics, chlorhexidine (CHX) and Rhizoma coptidis extract (RCE) would lead to cross-resistance or decreased susceptibility in Staphylococcus aureus . The S. aureus reference strain ATCC 25923 as well as 14 clinical isolates were exposed to antibiotics, CHX and RCE at sublethal doses for up to 14 days. Changes in susceptibility were determined by analysis of minimum inhibitory concentrations (MICs). All isolates were cross-resistant to more than one other antibiotic following tetracycline exposure, and increased resistance (≥4-fold MIC increase) to RCE and CHX was observed in six and three isolates, respectively. Following selection by CHX, most of the treated strains showed no significant change in sensitivity to CHX. However, all strains developed cross-resistance to at least one antibiotic, and decreased susceptibility (≥4-fold MIC increase) to RCE appeared in seven strains. Following exposure to RCE, 11 isolates showed cross-resistance to at least one antibiotic. In addition, three RCE-exposed strains showed reduced susceptibility to CHX (4- or 8-fold MIC increase). The results obtained in this study imply that antibiotics, biocides and antimicrobial Chinese herbs might employ some of the same mechanisms of action against bacteria, triggering mutual cross-resistance to further foster the development of bacterial resistance.
研究领域:
微生物学
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感染病学
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药理学
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分子生物学
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抗菌药物耐药性
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天然药物学
✓ 已验证
DOI
高影响因子
Scientific Reports
·
2025
·Vol. 15
·期 1
·40205
·
IF 3.9
Tang Cheng,Zou Yangyang,Meng Hao,Xu Jin,Long Fang,Chen Xiaoli,Xiao Qingling,Su Kelei,Nan Zhang,Guo Yaoyao,Li Chaojuan
To develop excipient-free carrier-free nanoparticles (DE NPs) via self-assembly of doxorubicin (DOX) and emodin (EMO) for enhanced combination chemotherapy against non-small cell lung cancer (NSCLC). DE NPs were fabricated through non-covalent interactions between DOX and EMO using a self-assembly method. The nanoparticles were characterized for morphology, stability, encapsulation efficiency, and cellular uptake. In vitro cytotoxicity and in vivo antitumor efficacy of free drugs (EMO, DOX), DOX/EMO mixture, and DE NPs were evaluated on A549 NSCLC cells. Mechanistic studies explored the role of DE NPs in suppressing efflux pump proteins via modulation of p65 activation and nuclear translocation. DE NPs formed rod-like nanostructures with high encapsulation efficiency (> 90%) and stability. They exhibited enhanced cellular uptake and intracellular drug accumulation compared to free drugs or the mixture. In vitro studies demonstrated significantly stronger cytotoxicity in A549 cells (IC50 reduction of ~ 50%) and a synergistic antitumor effect (combination index < 0.5). In vivo studies further confirmed the superior antitumor efficacy of DE NPs over individual DOX or EMO monotherapy (72.67 ± 7.20% tumor inhibition rate). Mechanistically, DE NPs inhibited p65 activation and nuclear translocation, downregulating efflux pump protein expression and prolonging drug retention in cancer cells. The excipient-free DE NPs provide a promising carrier-free nanomedicine platform for NSCLC treatment, achieving synergistic antitumor efficacy through enhanced drug delivery and suppression of drug resistance mechanisms. This strategy highlights the potential of self-assembled dual-drug nanoparticles to improve therapeutic outcomes in combination.
研究领域:
肿瘤学
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纳米医学
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药剂学
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分子肿瘤学
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转化医学
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药物递送
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耐药机制
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Virulence
·
2025
·
IF 5.4
Hao-Jie Shen,Jun-Feng Wang,Zheng-Jie Xue,Jia-Qi Shi,Bing Chen,Dong-Min Chen,Ni-Pi Chen,Yu-Dong Li,Chao-Dong Qian
Antimicrobial resistance is one of the greatest threats to global health. A thorough comprehension of the underlying processes through which bacteria evolve the ability to withstand diverse stressors is vital for the development of efficacious strategies to address this challenge. This study aimed to elucidate the mechanisms underlying the adaptation of an acrB-deficient strain of Escherichia coli ATCC 35218 (35218m) to sanguinarine (SAN), the main component of phytobiotic derived from Macleaya cordata. Analysis of the in vitro-selected SAN-resistant clones of strain 35218m led to the identification of a functionally uncharacterized TetR regulator, EefR. The regulator represses its own expression and that of four neighboring genes forming the eefRABCD operon, encoding components of a tripartite RND-efflux pump (EefABC) and a putative MFS-type exporter (EefD). Overexpression of these pumps reduces the susceptibility of acrB-deficient E. coli to SAN and structurally diverse antibiotics. The eefR-eefABC-eefD cluster, widely distributed across Enterobacteriaceae genomes, is also found on plasmids in several E. coli isolates, indicating a significant risk for the rapid spread of this multidrug resistance mechanism.
研究领域:
微生物学
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分子生物学
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耐药机制
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细菌遗传学
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抗生素耐药性
✓ 已验证
DOI
PubMed
高影响因子
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