用于细菌细胞成像和抗菌应用的金属响应性荧光团和阿米卡星共轭肝素。

IF 4 2区 医学 Q2 CHEMISTRY, MEDICINAL ACS Infectious Diseases Pub Date : 2024-11-11 DOI:10.1021/acsinfecdis.4c00740
Rama Karn, Sayantani Biswas, Soumya Srimayee, Anjali Patel, Suravi Chauhan, Debasis Manna
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引用次数: 0

摘要

细菌感染率的不断攀升给当前的全球医疗保健系统带来了严峻的挑战。以预期的灵敏度和选择性快速识别和量化细菌病原体,对于采取有针对性的治疗干预措施以减轻疾病负担、减少耐药性和进一步传播至关重要。与此同时,我们也迫切需要创新方法来对抗感染和抗生素耐药性。在此,我们展示了肝素(HP)共轭物的开发成果,该共轭物由 Zn2+ 诱导的 "开启 "荧光团 2-(吡啶-2-基)-1H-苯并[d]咪唑(PBI)修饰,通过与表面暴露的肝素结合蛋白(HPBs)特异性结合与细菌细胞相互作用,从而诱导荧光信号,对整个细菌细胞进行快速、选择性感测。此外,改性肝素聚合物(HP-PBI-Amk)中还加入了阿米卡星(Amk)抗生素,通过产生活性氧来增强其抗菌功效。尽管只有阿米卡星具有肾毒性,但将其加入生物聚合物中仍能保持其抗菌特性,同时提供生物兼容性。这项研究的结果表明,HP-PBI 和 HP-PBI-Amk 的开发分别为细菌检测和根除提供了有前途的策略,为未来的研究和临床应用提供了潜在的途径。
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Metal-Responsive Fluorophore and Amikacin-Conjugated Heparin for Bacterial Cell Imaging and Antibacterial Applications.

The escalating prevalence of bacterial infections presents a formidable challenge to current global healthcare systems. Rapid identification and quantification of bacterial pathogens with anticipated sensitivity and selectivity are crucial for targeted therapeutic interventions to mitigate disease burden, drug resistance, and further transmission. Concurrently, there is a pressing need to innovate novel approaches to combat infections and counter antibiotic resistance. Herein, we demonstrated the development of heparin (HP) conjugates modified with a Zn2+-induced "turn-on" fluorophore, 2-(pyridin-2-yl)-1H-benzo[d]imidazole (PBI), that interacts with bacterial cells via specific binding with the surface-exposed heparin-binding proteins (HPBs), thereby inducing fluorescence signals for rapid and selective sensing of whole bacterial cells. Additionally, amikacin (Amk) antibiotic was integrated into the modified heparin polymer (HP-PBI-Amk) to augment its antibacterial efficacy via reactive oxygen species generation. Despite the nephrotoxicity of only amikacin, its inclusion in the biopolymer retains its antibacterial properties while providing biocompatibility. The outcome of this study demonstrates the development of HP-PBI and HP-PBI-Amk as promising strategies for bacterial detection and eradication, respectively, offering potential avenues for future research and clinical applications.

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来源期刊
ACS Infectious Diseases
ACS Infectious Diseases CHEMISTRY, MEDICINALINFECTIOUS DISEASES&nb-INFECTIOUS DISEASES
CiteScore
9.70
自引率
3.80%
发文量
213
期刊介绍: ACS Infectious Diseases will be the first journal to highlight chemistry and its role in this multidisciplinary and collaborative research area. The journal will cover a diverse array of topics including, but not limited to: * Discovery and development of new antimicrobial agents — identified through target- or phenotypic-based approaches as well as compounds that induce synergy with antimicrobials. * Characterization and validation of drug target or pathways — use of single target and genome-wide knockdown and knockouts, biochemical studies, structural biology, new technologies to facilitate characterization and prioritization of potential drug targets. * Mechanism of drug resistance — fundamental research that advances our understanding of resistance; strategies to prevent resistance. * Mechanisms of action — use of genetic, metabolomic, and activity- and affinity-based protein profiling to elucidate the mechanism of action of clinical and experimental antimicrobial agents. * Host-pathogen interactions — tools for studying host-pathogen interactions, cellular biochemistry of hosts and pathogens, and molecular interactions of pathogens with host microbiota. * Small molecule vaccine adjuvants for infectious disease. * Viral and bacterial biochemistry and molecular biology.
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