Materials Today Bio
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2024
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IF 8.7
Gong Li,Lu Han,Li-Juan Xia,Ang Gao,Zhi-Peng Li,Shi-Ying Zhou,Lei Wan,Yao Deng,Tian-Hong Zhou,Xin-Yi Lu,Yang Luo,Dun-Sheng Liang,Gui-Ting Wu,Sheng-Qiu Tang,Xin-Lei Lian,Hao Ren,Xiao-Ping Liao,Liang Chen,Jian Sun
Plasmid-mediated conjugative transfer of antibiotic resistance genes (ARGs) within the human and animal intestine represents a substantial global health concern. linoleic acid (LA) has shown promise in inhibiting conjugation in vitro , but its in vivo effectiveness in the mammalian intestinal tract is constrained by challenges in efficiently reaching the target site. Recent advancements have led to the development of waterborne polyurethane nanoparticles for improved drug delivery. In this study, we synthesized four waterborne polyurethane nanoparticles incorporating LA (WPU@LA) using primary raw materials, including N-methyldiethanolamine, 2,2'-(piperazine-1,4-diyl) diethanol, isophorone diisocyanate, castor oil, and acetic acid. These nanoparticles, identified as WPU 0.89 @LA, WPU 0.99 @LA, WPU 1.09 @LA, and WPU 1.19 @LA, underwent assessment for their pH-responsive release property and biocompatibility. Among these, WPU 0.99 @LA displayed superior pH-responsive release properties and biocompatibility towards Caco-2 and IPEC-J2 cells. In a mouse model, a dosage of 10 mg/kg/day WPU 0.99 @LA effectively reduced the conjugation of IncX4 plasmids carrying the mobile colistin resistance gene ( mcr-1 ) by more than 45.1-fold. In vivo toxicity assessment demonstrated that 10 mg/kg/day WPU 0.99 @LA maintains desirable biosafety and effectively preserves gut microbiota homeostasis. In conclusion, our study provides crucial proof-of-concept support, demonstrating that WPU 0.99 @LA holds significant potential in controlling the spread of antibiotic resistance within the mammalian intestine.
研究领域:
药理学
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纳米技术
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微生物学
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生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
mSphere
·
2024
·
IF 3.7
Xiao-die Cui,Xiao-kang Liu,Xiao-yuan Ma,Shuai-hua Li,Jun-kai Zhang,Rong-jia Han,Kai-fang Yi,Jian-hua Liu,Yu-shan Pan,Dan-dan He,Gong-zheng Hu,Ya-jun Zhai
The appearance and prevalence of multidrug-resistance (MDR) Gram-negative bacteria (GNB) have limited our antibiotic capacity to control bacterial infections. The clinical efficacy of colistin (COL), considered as the “last resort” for treating GNB infections, has been severely hindered by its increased use as well as the emergence and prevalence of mobile colistin resistance (MCR)-mediated acquired drug resistance. Identifying promising compounds to restore antibiotic activity is becoming an effective strategy to alleviate the crisis of increasing MDR. We first demonstrated that the combination of berberine (BBR) and EDTA substantially restored COL sensitivity against COL-resistant Salmonella and Escherichia coli. Molecular docking indicated that BBR can interact with MCR-1 and the efflux pump system AcrAB-TolC, and BBR combined with EDTA downregulated the expression level of mcr-1 and tolC. Mechanically, BBR combined with EDTA could increase bacterial membrane damage, inhibit the function of multidrug efflux pump, and promote oxidative damage, thereby boosting the action of COL. In addition, transcriptome analysis found that the combination of BBR and EDTA can accelerate the tricarboxylic acid cycle, inhibit cationic antimicrobial peptide (CAMP) resistance, and attenuate Salmonella virulence. Notably, the combination of BBR and EDTA with COL significantly reduced the bacterial load in the liver and spleen of a mice model infected with Salmonella. Our findings revealed that BBR and EDTA can be used as adjuvants collectively with COL to synergistically reverse the COL resistance of bacteria.
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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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Engineering
·
2023
·
IF 12.8
Huangwei Song,Xueyang Wang,Muchen Zhang,Zhiyu Zou,Siyuan Yang,Tian Yi,Jianfeng Wang,Dejun Liu,Yingbo Shen,Chongshan Dai,Zhihai Liu,Timothy R. Walsh,Jianzhong Shen,Congming Wu,Yang Wang
The emergence and spread of the mobile colistin-resistance gene, mcr-1 , and its variants pose a challenge to the use of colistin, a last-resort antibiotic used to treat severe infections caused by extensively drug-resistant (XDR) Gram-negative pathogens. Antibiotic adjuvants are a promising strategy to enhance the efficacy of colistin against colistin-resistant pathogens; however, few studies have considered the effects of adjuvants on limiting resistance-gene transmission. We found that chelerythrine (4 mg∙L −1 ) derived from Macleaya cordata extract, which is used as an animal feed additive, reduced the minimal inhibitory concentration (MIC) of colistin against an mcr-1 positive E. coli strain by 16-fold (from 2 to 0.125 mg∙L −1 ), eliminated approximately 10 4 colony-forming units (CFUs) of an mcr-1 -carrying strain in a murine intestinal infection model, and inhibited the conjugation of an mcr-1 -bearing plasmid in vitro (by >100-fold) and in a mouse model (by up to 5-fold). A detailed analysis revealed that chelerythrine binds to phospholipids on bacterial membranes and increases cytoplasmic membrane fluidity, thereby impairing respiration, disrupting proton motive force (PMF), generating reactive oxygen species (ROS), and decreasing intracellular adenosine triphosphate (ATP) levels, which subsequently downregulates mcr-1 and conjugation-associated genes. These dual effects of chelerythrine can expand the use of antibiotic adjuvants and may provide a new strategy for circumventing mobile colistin resistance.
研究领域:
微生物学
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药理学
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抗菌素耐药性
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传染病学
✓ 已验证
产品关联
DOI
高影响因子
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