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
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DOI
高影响因子
MYCOPATHOLOGIA
·
2025
·Vol. 190
·期 5
·1-16
·
IF 2.9
Zhang Heng,Zhu Zhangling,Peng Mengqi,Liu Sijie,Gong Xiao,Chen Tian,Hu Qingwen,Li Linyun,Dun-zhu Zha-xi,Drol-ga Lha-zom,Sun Yi
Introduction Aspergillus fumigatus poses significant clinical challenges due to its increasing azole resistance. This study investigates the sdh1 gene's role in regulating azole susceptibility, mitochondrial function, and virulence. Materials and Methods Fungal strains were co-cultured with varying concentrations of succinate dehydrogenase inhibitors (SDHIs). Post-treatment azole minimum inhibitory concentrations (MICs) were determined using broth microdilution method, while succinate dehydrogenase subunit (SDH) expression changes were analyzed via RT-qPCR. Using A. fumigatus MFIG001 as the parental strain, sdh1 knockout mutant (Δ sdh1 ) and complemented strain (Δ sdh1::sdh1 + ) were constructed through homologous recombination. Detect the hyphal growth rate of Δ sdh1 , MICs and the changes in virulence within the Galleria mellonella infection model. Mitochondrial function was evaluated by measuring SDH activity, ATP content, and reactive oxygen species (ROS) levels. Transcriptomic changes were analyzed using RNA-seq and RT-qPCR, with efflux pump activity validated through Rhodamine 6G accumulation assays. Results Exposure to subinhibitory concentrations of SDHIs induced azole resistance in A. fumigatus , with 4.12% of strains exhibiting reduced susceptibility to voriconazole, itraconazole, and posaconazole. RT-qPCR analysis revealed significant downregulation of sdh1 in resistant strains, implicating its role in resistance development. Deletion of sdh1 resulted in an 8- to 16-fold increase in triazole MICs, confirming its role as a negative regulator of azole susceptibility. Phenotypically, the Δ sdh1 strain exhibited impaired growth, reduced sporulation, and diminished efficacy of azole treatment in the G. mellonella infection model. Furthermore, Δ sdh1 exhibited severe mitochondrial dysfunction, including reduced SDH activity, decreased ATP levels, elevated ROS, and impaired antioxidant defenses. RNA-seq analysis revealed that the deletion of sdh1 upregulated the expression of efflux pump genes (e.g., cdr1B , abcB , mdr4 ), while Rhodamine 6G efflux assays demonstrated significantly enhanced efflux activity. Discussion These results identify sdh1 as a critical determinant of azole susceptibility through dual mechanisms: mitochondrial function maintenance and efflux pump regulation. The observed SDHI-induced cross-resistance suggests agricultural fungicides may drive environmental selection of azole-resistant strains. While sdh1 deletion increased drug tolerance through efflux activation, the concurrent mitochondrial damage reduced pathogenic fitness, revealing compensatory evolutionary constraints. This work highlights the need to monitor non-target effects of agricultural SDHIs on clinical antifungal resistance.
研究领域:
医学真菌学
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抗真菌耐药
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分子微生物学
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环境与健康
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线粒体生物学
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药物相互作用
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感染性疾病
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产品关联
DOI
PubMed
高影响因子
CURRENT MICROBIOLOGY
·
2025
·Vol. 82
·期 10
·1-12
·
IF 2.6
Chen Chaoheng,Huang Yilan,Liao Yanke,Lan Sugui,Liang Zining,Yuan Jing,Tan Qiang
This study aimed to investigate the underlying mechanism of action and further identify main active ingredient by which Radix Paeoniae Rubra extracts (RPRE) inhibited the cross-resistance to tetracycline (TET), piperacillin (PIP), and gentamicin (GEN) mediated by Rhizoma Coptidis extracts (RCE) in Staphylococcus aureus (SA). Treatment with mixed solutions of RCE and RPRE resulted in disappearance of TET, PIP, or GEN resistance compared to what was shown with RCE treatment alone. Fifteen relevant resistant genes ( smrB , bmr3 , nhoA , BTN44_15030 , clpL , hisG , norA , fmtA_1 , emrB_1 , BTN44_07590 , paiA , icaR , BTN44_13995 , HMPREF0776_1664 and vraG ) were significantly downregulated compared to the RCE-induced mutants. RPRE was sequentially fractionated using macroporous resin and silica gel column chromatography, and all resulting eluates exhibited the antibacterial activity against Staphylococcus ATCC 25923. When exposed to RCE combined with either 30% EE or DCM:MeOH(5:1) eluates, no significant cross-resistance to the tested antibiotics was observed in the induced isolates. Similarly, the expression levels of the fifteen resistant genes were markedly reduced. Furthermore, gallic acid (GA) was identified in the two aforementioned eluates using HPLC–MS. After selection with a mixed solution of RCE and GA, the induced strains displayed no cross-resistance to the tested antibiotics, and the expression of the resistant genes was significantly decreased. These results suggest that GA is a key active ingredient in RPRE responsible for suppressing RCE-mediated cross-resistance to TET, PIP, and GEN in SA.
研究领域:
药理学
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微生物学
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分子生物学
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植物学
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抗菌药物耐药性
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产品关联
DOI
PubMed
高影响因子
APPLIED ORGANOMETALLIC CHEMISTRY
·
2020
·Vol. 34
·期 8
·e5680
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IF 3.14
Chunyan Jia,Yanwei Cong,Shaoping Pu,Linxiang Cai,Yunshuang Zhong,Xinzhong Zhang,Xiali Liao,Yamin Li,Bo Yang,Chuanzhu Gao
A series of mixed ammine/amine platinum(IV) complexes with lipophilic ligands in their axial positions were designed, synthesized, and spectrally characterized. In vitro cytotoxicity evaluation of these complexes and their lead compounds have been carried out against A549, SMMC-7721, MCF-7, and SW480 human cancer cell lines. The introduction of carboxylate ions as leaving group can improve the aqueous solubility and stability of the platinum(II) complexes. The carboxylato ligands and chloride ligands in the axial position markedly increased the lipophilicity and cytotoxicity of compounds C4 and C5. Particularly, compound C5 showed two to eight times higher cytotoxicity than cisplatin and satraplatin against selected cell lines. For its oral activity and no cross-resistance potentiality, C5 is expected to be an antitumor platinum drug candidate. This novel class of platinum compounds represents a valuable lead in the development of new-generation agents capable of demonstrating cytotoxicity superior to that of the clinically established cisplatin.
研究领域:
化学
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药学
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肿瘤学
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）