Experimental and Therapeutic Medicine
·
2019
·Vol. 18
·期 4
·2924-2932
·
IF 1.448
Jingjing Wang,Yongzhong Ning,Shu Li,Yun Wang,Jinhua Liang,Chunming Jin,Hairun Yan,Yongcun Huang
Acinetobacter baumannii is an important cause of hospital‑acquired, multidrug‑resistant (MDR) infections occurring worldwide. Anti‑microbial combination regimens may be the only feasible treatment option for affected patients. In the present study, the efficacy of the combined therapy of meropenem with colistin, ampicillin‑sulbactam, tazobactam and vancomycin against clinical strains of MDR A. baumannii was determined. Anti‑microbial susceptibility testing was performed and resistance genes were characterized by a multiplex polymerase chain reaction (PCR)‑reverse line blot assay. The genetic background of New Delhi metallo‑β‑lactamase 1 (NDM‑1) was analysed by primer walking. The presence of NDM‑1 was detected using the modified Hodge test and the EDTA‑combined disk test. To screen for synergistic drug effects, the fractional inhibitory concentration index was calculated using a checkerboard assay. The results of the PCR as well as the sequence analyses suggested that NDM‑1 was located downstream of the ISAba125 element. In addition, a synergistic effect was determined for meropenem + vancomycin, meropenem + tazobactam and meropenem + ampicillin + sulbactam in two strains each, and in four strains for meropenem + colistin. A total of five A. baumannii strains with resistance to numerous antibiotics and carrying numerous resistance genes were identified. In the strains of A. baumannii, the NDM‑1 gene was integrated in a transposon structure with a copy of the ISAba125 insertion sequence. However, the genetic background was not identical among the different species and strains. The genetic variability of NDM‑1 may facilitate the rapid dissemination of this gene. In conclusion, meropenem may enhance the efficacy of antibiotics in A. baumannii strains with NDM‑1‑associated MDR.
研究领域:
微生物学
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传染病学
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临床医学
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PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2025
·
IF 11.3
Yangcheng Ding,Shuangjing Dong,Danna Ding,Xiaoming Chen,Fangxi Xu,He Niu,Jixiao Xu,Yuhang Fan,Ruya Chen,Yijing Xia,Xiawen Qiu,Huajun Feng
Residual antibiotics in aquaculture ecosystems can exert selective pressures on bacterial communities, driving bacteria to acquire antibiotic resistance genes (ARGs) through gene mutations or horizontal gene transfer (HGT). This study investigated the antibiotic resistance risk in freshwater aquaculture ecosystems of Micropterus salmoides in Zhejiang Province. The results revealed that oxytetracycline, ciprofloxacin and florfenicol were up to 300 ng/L, and the proportion of multidrug-resistant genes varied from 32.20 % to 50.70 % in the surveyed aquaculture water. Additionally, approximately 9.80 % of all annotated ARGs were identified as possessing plasmid-mediated horizontal transfer risks. The ARGs host prediction revealed that Actinobacteria carried the highest abundance of ARGs, up to 159.38 (coverage, ×/Gb). Furthermore, the abundance of Paer_emrE , ksgA , ompR and golS were positively correlated with Chlorophyll a concentration ( p < 0.05), suggesting that algal blooms might facilitate the evolution and transfer of ARGs. Correlations between ARG abundances and total phosphorus, total nitrogen, pH, electrical conductivity indicated that modulating water quality parameters may serve as a viable strategy to mitigate the eco-environmental risk of ARGs in aquaculture water. This study identified antibiotic resistance characteristics in freshwater aquaculture ecosystems of Micropterus salmoides in Zhejiang Province, establishing a foundation on managing antibiotic resistance risks in such aquaculture environments.
研究领域:
环境科学
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微生物学
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水产养殖学
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PubMed
高影响因子
Frontiers in Pharmacology
·
2025
·
IF 4.8
Wen-Ba Wang,Jia-Yang Wan,Dao-Jun Yu,Hai-Xia Du,Hui-Fen Zhou,Hai-Tong Wan,Jie-Hong Yang
Introduction: Carbapenem-resistant Klebsiella pneumoniae (CRKp) infection poses a significant global public health challenge, with the misuse of antibiotics further contributing to the development of resistance and triggering harmful inflammatory responses. Outer membrane vesicles (OMVs) released by CRKp under sub-lethal concentration of MEM pressure (KOMV-MEM) exhibit enhanced virulence and greater efficiency in transferring resistance genes.Methods: We investigated the inhibitory effects of chlorogenic acid (CA) on KOMV-MEM characteristics and its protective role in KOMV-MEM infected mice. Based on LC-MS proteomic analysis of vesicles, we screened for potential targets of KOMV-MEM in promoting macrophage (MØ) pyroptosis pathways and inducing resistance gene transfer. Subsequently, computational predictions and experimental validation were performed to determine how CA regulates these mechanisms.Results: This study confirmed that, under MEM pressure, the exacerbated infection levels in CRKp-inoculated mice are attributable to the high virulence of KOMV-MEM. Computational and experimental results demonstrated that CA inhibits pyroptosis by reducing MØ capture of KOMV-MEM through blocking the interaction between GroEL and LOX-1. Furthermore, CA prevents the spread of resistance genes by disrupting the conjugation and transfer processes between KOMV-MEM and recipient bacteria. Finally, in vitro and in vivo assays showed that CA inhibits KOMV-MEM resistance enzymes, thereby preventing the hydrolysis of MEM in the environment and depriving susceptible bacteria of protection.Discussion: These findings provide the first confirmation that CA can inhibit both the virulence and the transmission of drug resistance in KOMV-MEM. This underscores the potential of CA treatment as a promising antimicrobial strategy against CRKp infection.
研究领域:
微生物学
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药理学
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感染与免疫
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PubMed
高影响因子
Frontiers in Microbiology
·
2025
·
IF 4.5
Zhuocheng Yao,Yuhan Yang,Yanchun Gong,Shiyi Shi,Yunying Ge,Weiliang Zeng,Deyi Zhao,Jianming Cao,Tieli Zhou,Mo Shen
Disinfectants are commonly utilized by humans to combat microorganisms. However, residual disinfectants may promote environmental antimicrobial resistance by facilitating horizontal gene transfer (HGT) of antibiotic resistance genes. Bronopol is a routinely used disinfectant that persists in the environment, and previous studies have concentrated on its ecotoxicity rather than its implications on the propagation of resistance genes. This study aimed to establish an in vitro conjugation model to investigate whether bronopol promotes the transfer of antibiotic resistance genes (ARGs) via plasmid conjugation. Using Escherichia coli DH5α and DC8855 as donors harboring RP4-7 and blaNDM-4-positive IncFII(K) plasmids, respectively, and J53 as the recipient strain, we found that sub-inhibitory concentrations of bronopol (2 μg/L and 20 μg/L) significantly increased the conjugative transfer frequency (CTF) of both plasmids. Mechanistic analysis revealed that bronopol enhanced bacterial membrane permeability, as demonstrated by propidium iodide (PI) staining, 1-N-phenylnaphthylamine (NPN) fluorescent probes, transmission electron microscopy (TEM), and upregulation of the outer membrane protein gene ompC. Additionally, bronopol treatment upregulated RP4 plasmid-encoded genes involved in DNA transfer/replication (trfAp) and the global regulator of HGT (kilA/kilB). These findings highlight a previously unrecognized role of bronopol in facilitating the dissemination of antibiotic resistance genes, particularly those of clinical significance.
研究领域:
微生物学
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环境科学
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遗传学
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PubMed
高影响因子
Water
·
2023
·Vol. 15
·期 17
·3047
·
IF 3.4
Lingyun Tian,Hao Fang,Qianbo Mao,Yi Bai,Zirui Ye,Dingjun Hu,Xiaoheng Wang,Yiyu Hou,Nan Ye,Shuai Zhang,Yan Ma
Antibiotic resistance poses a significant threat to the public health domain. A favorable platform for generating and disseminating antibiotic-resistant genes (ARGs) and antibiotic-resistant bacteria (ARB) is provided by landscaped fish ponds created by urbanization. This research delved into the effects exerted by different concentrations of specific antibiotics, namely tetracycline and ciprofloxacin, on the microbial community composition present in water samples obtained from a landscape pond. Additionally, we analyzed the abundance of ARGs and the class 1 integron-integrase gene (intI1), and identified potential hosts of ARGs. The results indicated that the consistent administration of antibiotics significantly influenced the microbial community structure, resulting in variations within both bacterial communities and functionalities. Furthermore, the absolute quantities of ARGs, includingtetA,tetC,qnrA, andqnrS, as well as the integrase geneintI1, exhibited augmentation in response to varying types and concentrations of antibiotics. Notably, the regular input of low concentrations of antibiotics produced higher levels of abundance of ARGs than the regular input of higher concentrations of antibiotics. The use of different types of antibiotics led to diverse host bacteria structures.
研究领域:
环境科学
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微生物学
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公共卫生
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高影响因子
BMC MICROBIOLOGY
·
2025
·Vol. 25
·期 1
·805
·
IF 4.2
Zhou Qianyu,Xue Jinjing,Li Jun,Liu Zhiying,Zou Yinuo,Dai Rui,Gu Kuan,Zhou Yonglin
The advent and global spread of plasmid-carried resistance genes, including the tigecycline resistance gene tet (X3/X4) and the colistin resistance gene mcr-1 , present a substantial threat to public health that requires immediate resolution. This study successfully screened and identified commercial anti-parasitic drugs that efficiently inhibit Tet(X4) enzyme activity (IC 50 = 79.42 µg/mL), revealing that mefloquine exhibited a synergistic antibacterial effect with tetracyclines against tet (X3/X4)-positive bacteria (FIC < 0.5) and an additive effect with tetracyclines against tet (X3/X4)-negative bacteria (0.5 < FIC < 1, excluding minocycline). Molecular dynamics simulations and checkerboard minimum inhibitory concentration (MIC) tests on Tet(X4) mutants in amino acid residues demonstrated that mefloquine’s interaction with the active site of Tet(X4) reduces its activity. The energy contribution of the binding site residues involves PHE221, PHE316, GLY233, PRO315, PHE232, MET212, ALA222 and HIE231, which establish robust interactions with mefloquine (Δ Etotal of ≤ − 0.5 kcal/mol). Moreover, findings from metabonomics, bacterial membrane analysis, ROS detection, NAD + /NADH ratio determination, and intracellular ATP determination indicated that mefloquine may significantly influence bacterial energy metabolism ( P < 0.05). Furthermore, in the mouse infection model of E. coli 47EC, the combination of methacycline and mefloquine, demonstrated significant therapeutic advantages, as evidenced by an increased survival rate (from 20.00% to 80.00%), decreased sepsis score, and decreased bacterial load. Our work is the first to reveal that the commercial medicine mefloquine can prolong the efficacy of tetracycline and treat infections caused by drug-resistant Enterobacteriaceae in clinical environments. Graphical
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Frontiers in Microbiology
·
2020
·
IF 4.236
Wen Zewen,Shang Yongpeng,Xu Guangjian,Pu Zhangya,Lin Zhiwei,Bai Bing,Chen Zhong,Zheng Jinxin,Deng Qiwen,Yu Zhijian
Opportunistic infections caused by multidrug-resistant Enterococcus faecalis strains are a significant clinical challenge. Eravacycline (Erava) is a synthetic fluorocycline structurally similar to tigecycline (Tige) that exhibits robust antimicrobial activity against Gram-positive bacteria. This study investigated the in vitro antimicrobial activity and heteroresistance risk of Eravacycline (Erava) in clinical E. faecalis isolates from China along with the mechanism of Erava resistance. A total of 276 non-duplicate E. faecalis isolates were retrospectively collected from a tertiary care hospital in China. Heteroresistance to Erava and the influence of tetracycline (Tet) resistance genes on Erava susceptibility were examined. To clarify the molecular basis for Erava resistance, E. faecalis variants exhibiting Erava-induced resistance were selected under Erava pressure. The relative transcript levels of six candidate genes linked to Erava susceptibility were determined by quantitative reverse-transcription PCR, and their role in Erava resistance and heteroresistance was evaluated by in vitro overexpression experiments. We found that Erava minimum inhibitory concentrations (MICs) against clinical E. faecalis isolates ranged from ≤0.015 to 0.25 mg/l even in strains harboring Tet resistance genes. The detection frequency of Erava heteroresistance in isolates with MICs ≤ 0.06, 0.125, and 0.25 mg/l were 0.43% (1/231), 7.5% (3/40), and 0 (0/5), respectively. No mutations were detected in the 30S ribosomal subunit gene in Erava heteroresistance-derived clones, although mutations in this subunit conferred cross resistance to Tige in Erava-induced resistant E. faecalis. Overexpressing RS00630 (encoding a bone morphogenetic protein family ATP-binding cassette transporter substrate-binding protein) in E. faecalis increased the frequency of Erava and Tige heteroresistance, whereas RS12140, RS06145, and RS06880 overexpression conferred heteroresistance to Tige only. These results indicate that Erava has potent in vitro antimicrobial activity against clinical E. faecalis isolates from China and that Erava heteroresistance can be induced by RS00630 overexpression.
研究领域:
微生物学
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药理学
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临床医学
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PubMed
高影响因子
Analytical Methods
·
2025
·
IF 2.6
Shenglong Ma,Baowei Zhao,Yunxia Li,Hui Liu,Rui Zhang
Antibiotic resistance genes (ARGs) are emerging pollutants that pose significant threats to both the environment and human health. Rapid detection of ARGs is essential for monitoring their levels and controlling their spread. However, traditional detection methods are often time-consuming and require specialized equipment, leading to delays. To address this issue, this study developed a novel method for visual microarray detection of ARGs, including sul1, tetA, qepA, macB, and vanR. This method employs ARG-specific dual probes combined with silver staining signal cascade amplification technology. A centrifuge-free concentration device has been developed that can directly enrich nucleic acid fragments from environmental samples, with traditional nucleic acid extraction and PCR amplification being eliminated. Using a dual probe combined with silver staining enhancement dual probe amplification technology, rapid high-throughput detection of low-concentration ARG is achieved. No specialized equipment is required, and on-site visual detection of ARG was realized. The detection method can detect target genes (sul1, tetA, qepA, macB, and vanR) within a concentration range of 0.411 µg mL−1 to 55.9 µg mL−1, with the lowest detectable target gene concentration being 0.411 µg mL−1. This study marks the first integration of a centrifuge-free concentration device, specific dual probes, and silver staining signal cascade amplification technology to establish a rapid visual detection method for ARGs using a microarray. The developed detection method holds significant potential not only for the detection and monitoring of ARGs but also as a prototype for devising future detection strategies.
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高影响因子
Frontiers in Microbiology
·
2024
·
IF 4
Zhou Haibo,Lu Zhaoxin,Liu Xinmei,Bie Xiaomei,Cui Xinping,Wang Zuwei,Sun Xiaojie,Yang Jun
Objectives: The purpose of this study was to determine the structural features and transferability of the multidrug-resistance (MDR) plasmid, and resistance phenotypes for the tested antimicrobials in foodborne Vibrio parahaemolyticus.Methods: Plasmids were isolated from a V. parahaemolyticus strain of seafood origin, then sequenced using the Illumina NovaSeq 6000 and PacBio Sequel II sequencing platforms to obtain the complete genome data. Characterization of the MDR plasmid pVP52-1, including determination of antimicrobial resistance genes (ARGs), plasmid incompatibility groups, and transferability, was carried out.Results: V. parahaemolyticus strain NJIFDCVp52 contained two circular chromosomes and two circular plasmids (pVP52-1 and pVP52-2). Plasmid typing indicated that pVP52-1 belonged to the incompatibility group IncA/C2 and the sequence type pST3. pVP52-1 carried 12 different ARGs, an IS110-composite transposon consisting of aac(6′)-Ib-cr, qnrVC1, aac(6′)-Ib, dfrA14, and the IS26-mphA-IS6100 unit flanked by inverted sequences of IS5075 and IS4321. pVP52-2 carried no ARGs. A plasmid elimination assay showed that only pVP52-1 and its ARGs were lost, the loss of resistance to several antimicrobials, causing a change from the ampicillin-ampicillin/sulbactam-cefazolin-cefoxitin-ceftazidime-cefotaxime-imipenem-trimethoprim/sulfamethoxazole resistance pattern to the ampicillin resistance pattern. In accordance, a conjugation transfer assay showed that only pVP52-1 and its ARGs were horizontally transferred, leading to increased antimicrobial resistance in Escherichia coli strain EC600, causing a change from the ampicillin-nalidixic acid resistance pattern to the ampicillin-ampicillin/sulbactam-cefazolin-cefoxitin-ceftazidime-cefotaxime-imipenem-nalidixic acid-chloramphenicol-tetracycline-trimethoprim/sulfamethoxazole-azithromycin resistance pattern. Further transferability experiments revealed that pVP52-1 could be transferred to other enterobacterial strains of E. coli and Salmonella.Discussion: This study emphasizes the urgent need for continued surveillance of resistance plasmids and changes in antimicrobial resistance profiles among the V. parahaemolyticus population.
研究领域:
微生物学
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分子生物学
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食品安全
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抗菌素耐药性
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PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-15
·
IF 12.6
Zhang Tao,Liu Guiling,Sun Siwei,Meng Zongwu,Qiu Yuzhe,Ding Ping
The antibiotic residues pose significant risks for bacterial resistance. To address the practical requirements for rapid, accurate, and on-site detection of antibiotic residues and monitoring the abundance of associated resistance genes, we report a smartphone-integrated multi-mode platform. The platform is aimed to simultaneous, accurate, and visual quantitative detection of ampicillin (AMP) and β-lactam antibiotic resistance genes (blaTEM). Specifically, we developed a magnetically controlled fluorescence, colorimetric, and photothermal biosensor based on a magnetic separation unit (aminated modified complementary DNA chain (NH2-cDNA) loading on the surface of Ferrosoferric Oxide@polydopamine (Fe3O4@PDA, FP), FP@cDNA) and a signal unit (the aptamer nucleic acid chain modified by phosphate group linked to Prussian blue@UiO-66@manganese dioxide (PB@UiO-66@MnO2, PUM) through Zr-O-P bond, PUM@Apt), for the integrated detection of AMP and blaTEM. By utilizing complementary base pairing between FP@cDNA and PUM@Apt, along with precise aptamer recognition the AMP, we achieved the fluorescence quantitative detection of AMP by measuring the signal unit in the supernatant. Subsequently, the difference of signal units in colorimetric process leads to a varying conversion rate of oxidized 3,3’,5,5’-Tetramethylbenzidine (oxTMB), enabling the output of colorimetric and photothermal signals. The competitive binding of aptamers permitting the determination of AMP in the range of 0–160 pM with a low detection limit (0.34 pM). Additionally, in the presence of blaTEM, the activated CRISPR/Cas12a indiscriminately cleaves the single-stranded portion of the FP@DNA@PUM complex obtained by magnetic separation. A PUM-based three-signal detection scheme was established for the sensitive determination of blaTEM with the limit of detection (LOD) of 1.03 pM. The integration of smartphone-assisted analysis broadens the potential of the platform for visual detection. Notably, the innovative platform, with its excellent stability, exhibits great potential as a simple yet robust approach for the simultaneously visually monitoring antibiotics and drug resistance genes, and holds promise in the field of kit development.
研究领域:
生物化学
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分子生物学
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分析化学
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医学诊断
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PubMed
高影响因子
FOOD CHEMISTRY
·
2025
·
IF 9.8
Qian Han,Yingbo Cao,Xueran Shi,Tiance Gu,Zhuohao Jiao,Fan Xu,Zhuozhe Li,Jing Wang
Antibiotic resistance genes (ARGs) pose a significant threat to food safety and human health, underscoring the urgent need for their sensitive and convenient detection. Herein, a “switch-on” electrochemiluminescence (ECL) biosensor is fabricated based on the heterogenized porphyrinic hydrogen-bonded organic framework (PFC-45) as the ECL luminophor and ZnO as the co-reactant accelerator for tetracycline resistant gene ( tetA ) assay. The hetero-ligand PFC-45 effectively performs an intrareticular charge transfer and suppresses aggregation-caused quenching, showing 2.5- and 101.5-fold higher ECL intensity in aqueous solution than that of mono-ligand 5,10,15,20-tetra(4-carboxyphenyl) porphine (TCPP) and 5,10,15,20-tetra(4-pyridyl) porphine (TPyP)-based HOF. Combined with Exonuclease III-assisted target recycling amplification, the proposed biosensor achieves a good specificity and sensitivity for tetA detection with a low detection limit of 65.02 fM. This work expands the application of mixed-ligand porphyrin-based HOFs in ECL sensing and establishes a generalizable paradigm for monitoring antibiotic resistance through target-driven nucleic acid signal amplification.
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Biosensors-Basel
·
2023
·Vol. 13
·期 8
·764
·
IF 5.4
Ruiting Chen,Hejing Chen,Huaping Peng,Yanjie Zheng,Zhen Lin,Xinhua Lin
Drug resistance in cancer is associated with overexpression of the multidrug resistance (MDR1) gene, leading to the failure of cancer chemotherapy treatment. Therefore, the establishment of an effective method for the detection of the MDR1 gene is extremely crucial in cancer clinical therapy. Here, we report a novel DNA biosensor based on an aligned multi-walled carbon nanotube (MWCNT) array modified electrode with 3D nanostructure for the determination of the MDR1 gene. The microstructure of the modified electrode was observed by an atomic force microscope (AFM), which demonstrated that the electrode interface was arranged in orderly needle-shaped protrusion arrays. The electrochemical properties of the biosensor were characterized by cyclic voltammetry (CV), differential pulse voltammetry (DPV), and electrochemical impedance spectroscopy (EIS). Chronocoulometry (CC) was used for the quantitative detection of the MDR1 gene. Taking advantage of the good conductivity and large electrode area of the MWCNT arrays, this electrochemical DNA sensor achieved a dynamic range from 1.0 × 10−12M to 1.0 × 10−8M with a minimal detection limit of 6.4 × 10−13M. In addition, this proposed DNA biosensor exhibited high sensitivity, selectivity, and stability, which may be useful for the trace analysis of the MDR1 gene in complex samples.Keywords:multidrug resistant gene;multi-walled carbon nanotube array;electrochemical DNA biosensor;3D sensing interface
研究领域:
生物工程
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分析化学
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生物医学工程
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分子生物学
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高影响因子
危险品化学品经营许可证（带存储）