Antimicrobial resistance

抗菌素耐药性
  • 文章类型: Journal Article
    抗菌素耐药性(AMR)对人类构成了多方面的威胁,动物,和环境部门。作为回应,自2000年代以来,中国制定了一系列政策。到目前为止,没有对这些政策文件进行全面评估。本研究旨在使用涵盖三个领域的治理框架在国家一级审查AMR政策文件的内容:政策设计;实施工具;以及监测和评估。从2003年到2022年,我们确定了44份来自政府机构网站的AMR文件。我们的发现揭示了三个治理领域的明显差异。应加强政策设计和监测评价领域,特别是在“协调”领域,\'问责制\',\'可持续性\',和“有效性”。从“一个健康”的角度来看,与人类和动物部门相比,环境部门受到的关注较少。有效应对这些挑战需要不同利益攸关方的更坚定承诺和广泛支持。
    Antimicrobial resistance (AMR) poses a multifaceted threat to the human, animal, and environment sectors. In response, China has formulated a series of policies since the 2000s. Thus far, there has been no comprehensive assessment of these policy documents. This study aims to review the content of AMR policy documents at the national level using a governance framework covering three areas: Policy Design; Implementation Tools; and Monitoring and Evaluation. We identified 44 AMR documents from 2003 to 2022 sourced from government agency websites. Our findings have revealed noticeable discrepancies across the three governance areas. The Policy Design and Monitoring and Evaluation areas should be strengthened, particularly in the domains of \'Coordination\', \'Accountability\', \'Sustainability\', and \'Effectiveness\'. From a \'One Health\' perspective, the environment sector has received less attention compared to the human and animal sectors. Effectively addressing these challenges requires a stronger commitment and widespread support from diverse stakeholders.
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  • 文章类型: Journal Article
    抗生素耐药性逐渐削弱了传统抗生素的有效性。必须停止临床治疗。因此,迫切需要新型抗菌剂。我们回顾了2002-2023年期间发表的关于抗菌药物的研究。这些研究大多是在过去10年中发表的。通过分析最近关于抗生素耐药性和新抗菌药物开发的文章,我们表明,尽管抗药性是不可避免的,通过抗菌肽的发现和临床应用,纳米材料药物,和噬菌体疗法.鉴于抗菌素耐药性的出现,新的抗微生物剂的开发将需要在依赖传统发现和开发方法的领域进行创新。
    Antibiotic resistance has progressively diminished the effectiveness of conventional antibiotics, necessitating the cessation of clinical treatment. Consequently, novel antibacterial agents are urgently needed. We review studies on antimicrobial agents published during 2002-2023. Most of these studies were published within the last 10 years. By analyzing recent articles on antibiotic resistance and the development of new antibacterial drugs, we showed that although drug resistance is inevitable, the issue is being addressed gradually via the discovery and clinical application of antimicrobial peptides, nanomaterial drugs, and bacteriophage therapy. In light of the emergence of antimicrobial resistance, the development of new antimicrobial agents will require innovation in a field that has relied on traditional methods of discovery and development.
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  • 文章类型: Journal Article
    肺炎克雷伯菌,一种以引起严重感染而闻名的主要临床病原体,由于其不断升级的抗生素耐药性,引起了越来越多的关注。噬菌体正在成为抗生素的有希望的替代品;然而,它们对特定宿主的特异性通常限制了它们的使用。在这项研究中,获得114个噬菌体的集合,并对238个临床肺炎克雷伯菌菌株进行分析,揭示了一系列裂解行为。推定的尾部蛋白簇与裂解模式之间的相关性导致发现了六个受体结合蛋白(RBP)簇,这些簇决定了宿主胶囊的嗜性。重要的是,鉴定了具有跨囊裂解能力的RBP。新识别的RBP提供了一个工具箱,用于定制针对不同胶囊类型的噬菌体。建立在工具箱上,具有改变的RBPs的工程噬菌体成功地改变并扩大了它们的宿主囊向性,为可调噬菌体奠定基础,为对抗肺炎克雷伯菌感染提供精确和灵活的解决方案。
    Klebsiella pneumoniae, a major clinical pathogen known for causing severe infections, is attracting heightened attention due to its escalating antibiotic resistance. Phages are emerging as a promising alternative to antibiotics; however, their specificity to particular hosts often restricts their use. In this study, a collection of 114 phages is obtained and subjected to analysis against 238 clinical K. pneumoniae strains, revealing a spectrum of lytic behaviors. A correlation between putative tail protein clusters and lysis patterns leads to the discovery of six receptor-binding protein (RBP) clusters that determine host capsule tropism. Significantly, RBPs with cross-capsular lysis capabilities are identified. The newly-identified RBPs provide a toolbox for customizing phages to target diverse capsular types. Building on the toolbox, the engineered phages with altered RBPs successfully shifted and broadened their host capsule tropism, setting the stage for tunable phage that offer a precise and flexible solution to combat K. pneumoniae infections.
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  • 文章类型: Journal Article
    抗菌素耐药性(AMR)是主要的公共卫生威胁,细菌快速传播抗菌药物耐药基因(ARG)的能力加剧了这种情况。由于不相容组P(IncP)的共轭质粒是普遍存在的可移动遗传元件,通常携带ARG并且宿主范围广,它们是防止AMR传播的重要目标。质粒依赖性噬菌体通过将接合分泌系统的成分识别为受体来感染携带质粒的细菌。我们试图使用携带共轭IncP质粒pKJK5的肠沙门氏菌无毒菌株从废水中分离出依赖质粒的噬菌体。无论该网站,我们仅获得了属于Alphatectivirus属的噬菌体。对11个分离株进行了测序,他们的基因组分析,以及使用S.enterica建立的宿主范围,大肠杆菌,和携带不同共轭质粒的恶臭假单胞菌。我们证实,使用依赖培养和不依赖培养的方法,Alphatectivirus在家庭和医院废水中含量丰富。然而,这些结果与它们在宏基因组中的低发生或检测不到不一致.因此,总的来说,我们的结果强调了进行噬菌体分离以揭示多样性的重要性,特别是考虑到质粒依赖性噬菌体减少接合质粒携带的ARG传播的潜力,并帮助对抗AMR危机。
    Antimicrobial resistance (AMR) is a major public health threat, exacerbated by the ability of bacteria to rapidly disseminate antimicrobial resistance genes (ARG). Since conjugative plasmids of the incompatibility group P (IncP) are ubiquitous mobile genetic elements that often carry ARG and are broad-host-range, they are important targets to prevent the dissemination of AMR. Plasmid-dependent phages infect plasmid-carrying bacteria by recognizing components of the conjugative secretion system as receptors. We sought to isolate plasmid-dependent phages from wastewater using an avirulent strain of Salmonella enterica carrying the conjugative IncP plasmid pKJK5. Irrespective of the site, we only obtained bacteriophages belonging to the genus Alphatectivirus. Eleven isolates were sequenced, their genomes analyzed, and their host range established using S. enterica, Escherichia coli, and Pseudomonas putida carrying diverse conjugative plasmids. We confirmed that Alphatectivirus are abundant in domestic and hospital wastewater using culture-dependent and culture-independent approaches. However, these results are not consistent with their low or undetectable occurrence in metagenomes. Therefore, overall, our results emphasize the importance of performing phage isolation to uncover diversity, especially considering the potential of plasmid-dependent phages to reduce the spread of ARG carried by conjugative plasmids, and to help combat the AMR crisis.
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  • 文章类型: Journal Article
    这项研究旨在创新一种基于纳米酶的治疗策略,该策略将聚集诱导的发射(AIE)光敏剂与铜纳米酶相结合。这种方法旨在解决细菌感染中经常出现的缺氧状况,旨在通过确保足够的氧气供应来产生活性氧(ROS)来提高光动力疗法(PDT)的有效性。
    我们的方法涉及二羟基三苯基乙烯基吡啶(DHTPY)-Cu@唑来膦酸(ZOL)纳米酶颗粒的合成。我们最初合成了DHTPY,然后将其与铜纳米酶结合形成DHTPY-Cu@ZOL复合材料。纳米酶的大小,形态学,使用各种技术表征化学性质,包括动态光散射,透射电子显微镜,和X射线光电子能谱。我们进行了一系列的体外和体内测试,以评估光动力,抗菌,DHTPY-Cu@ZOL纳米酶的伤口愈合特性,包括它们的氧气产生能力,ROS生产,和对耐甲氧西林金黄色葡萄球菌(MRSA)的抗菌效果。
    DHTPY-Cu@ZOL表现出熟练的H2O2清除和氧气生成,在缺氧感染环境中增强PDT至关重要。我们的体外分析显示对MRSA有显著的抗菌作用,表明纳米酶有可能破坏细菌细胞膜。Further,使用MRSA感染伤口的糖尿病大鼠模型进行的体内研究表明,DHTPY-Cu@ZOL显着改善了伤口愈合并减少了细菌的存在,强调其作为慢性感染的非抗生素方法的功效。
    我们的研究表明,DHTPY-Cu@ZOL是一种非常有前途的对抗抗生素抗性微生物病原体和生物膜的方法。这些纳米酶颗粒的生物相容性和稳定性,加上其改善的PDT疗效使他们成为临床应用的有希望的候选人。
    UNASSIGNED: This research was to innovate a nanozyme-based therapeutic strategy that combines aggregation-induced emission (AIE) photosensitizers with copper nanozymes. This approach is designed to address the hypoxic conditions often found in bacterial infections and aims to boost the effectiveness of photodynamic therapy (PDT) by ensuring sufficient oxygen supply for reactive oxygen species (ROS) generation.
    UNASSIGNED: Our approach involved the synthesis of dihydroxyl triphenyl vinyl pyridine (DHTPY)-Cu@zoledronic acid (ZOL) nanozyme particles. We initially synthesized DHTPY and then combined it with copper nanozymes to form the DHTPY-Cu@ZOL composite. The nanozyme\'s size, morphology, and chemical properties were characterized using various techniques, including dynamic light scattering, transmission electron microscopy, and X-ray photoelectron spectroscopy. We conducted a series of in vitro and in vivo tests to evaluate the photodynamic, antibacterial, and wound-healing properties of the DHTPY-Cu@ZOL nanozymes, including their oxygen-generation capacity, ROS production, and antibacterial efficacy against methicillin-resistant Staphylococcus aureus (MRSA).
    UNASSIGNED: The DHTPY-Cu@ZOL exhibited proficient H2O2 scavenging and oxygen generation, crucial for enhancing PDT in oxygen-deprived infection environments. Our in vitro analysis revealed a notable antibacterial effect against MRSA, suggesting the nanozymes\' potential to disrupt bacterial cell membranes. Further, in vivo studies using a diabetic rat model with MRSA-infected wounds showed that DHTPY-Cu@ZOL markedly improved wound healing and reduced bacterial presence, underscoring its efficacy as a non-antibiotic approach for chronic infections.
    UNASSIGNED: Our study suggests that DHTPY-Cu@ZOL is a highly promising approach for combating antibiotic-resistant microbial pathogens and biofilms. The biocompatibility and stability of these nanozyme particles, coupled with their improved PDT efficacy position them as a promising candidate for clinical applications.
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  • 文章类型: Journal Article
    肠沙门氏菌是世界范围内与人类沙门氏菌病相关的重要食源性病原体。进行了回顾性筛查以阐明患病率,抗菌素耐药性,和该病原体在上海的系统发育特征,中国。鼠伤寒沙门氏菌分离株是从2007-2019年收集的2,211株血清分型沙门氏菌分离株中选择的。在上海16个地区中的15个地区检测到二百七十七株鼠伤寒沙门氏菌。值得注意的是,214(77.3%)个分离株对多种药物耐药,32(11.6%)个分离株对环丙沙星耐药,5(1.8%)个分离株对头孢曲松进一步耐药。Poisson广义线性混合模型结果显示,2017年和2018年的多药耐药性(MDR)明显高于2010年(P<0.05),强调MDR风险的增加。系统发育结果表明,401个测序的鼠伤寒沙门氏菌分离株的全球数据集被分为四个克隆(ST36,ST313,ST19和ST34),出现在国际克隆传播中。来自中国的ST34分离株分为两个分支,ST34C1和ST34C2,后者可能来自上海,然后在全国范围内扩张,伴有超广谱β-内酰胺酶基因blaCTX-M-14和gyrA87位点喹诺酮耐药决定区的突变。此外,在InCI(Gamma)样质粒中发现了blaCTX-M-14与ISECp1上游和ΔIS903B下游连接,质粒接合有助于其水平传播。据我们所知,这是鼠伤寒沙门氏菌的流行病学和系统发育特征的第一份报告,包括在上海出现的进化枝ST34C2,保证对这种高风险病原体进行监测的必要性。
    目的:我们的研究发现,在10年期间,上海广泛分布的肠道沙门菌血清型鼠伤寒沙门氏菌菌株伴随着抗菌药物耐药性(AMR)尤其是MDR的增加。填补了上海市长期持续监测该病原体AMR的空白。同时,我们鉴定了一种新的鼠伤寒沙门氏菌进化枝ST34C2,获得了由广谱β-内酰胺酶基因blaCTX-M-14以及gyrA87突变介导的IncI(γ)样质粒,以前没有报道过。值得注意的是,IncI(Gamma)样质粒首次在鼠伤寒沙门氏菌中报道,结合可以加速抗微生物抗性基因blaCTX-M-14的传播。这些关于流行病的发现,抗菌素耐药性,以及鼠伤寒沙门氏菌的系统基因组特征为其对公众健康的潜在风险提供了有价值的见解,也是未来上海AMR预防和控制策略的基础。
    Salmonella enterica serovar Typhimurium is an important foodborne pathogen associated with human salmonellosis worldwide. A retrospective screening was performed to elucidate the prevalence, antimicrobial resistance, and phylogenomic characterization of this pathogen in Shanghai, China. S. Typhimurium isolates were selected from 2,211 serotyped Salmonella isolates collected during 2007-2019. Two hundred and seventy-seven S. Typhimurium isolates were detected in 15 of 16 districts in Shanghai. It was noted that 214 (77.3%) isolates were multi-drug resistant and 32 (11.6%) isolates were resistant to ciprofloxacin and 5 (1.8%) isolates were further resistant to ceftriaxone. Poisson generalized linear mixed model results showed that the multi-drug resistance (MDR) in 2017 and 2018 was significantly higher than that in 2010 (P<0.05), highlighting an increase in the risk of MDR. Phylogenetic results showed that a global data set of 401 sequenced S. Typhimurium isolates was classified into four clones (ST36, ST313, ST19, and ST34), which appeared in international clonal dissemination. The ST34 isolates from China fell into two clades, ST34C1 and ST34C2, the latter of which might originate from Shanghai, and then expanded nationally, accompanied by extended-spectrum β-lactamase gene blaCTX-M-14 and a mutation in quinolone resistance-determining region of the gyrA 87 site. Furthermore, blaCTX-M-14 linking to ISEcp1 upstream and ΔIS903B downstream was found in IncI (Gamma)-like plasmids, and the plasmid conjugation contributed to its horizontal transmission. To our knowledge, it is the first report of the epidemiological and phylogenetic characterization for S. Typhimurium including the emerged clade ST34C2 in Shanghai, warranting the necessity of surveillance for this high-risk pathogen.
    OBJECTIVE: Our study uncovered a widespread distribution of Salmonella enterica serovar Typhimurium isolates in Shanghai accompanied by the increase in antimicrobial resistance (AMR) especially MDR during a 10-year period, which filled in the gap about a long period of continuous monitoring of AMR in this pathogen in Shanghai. Meanwhile, we identified a new clade ST34C2 of S. Typhimurium with the acquisition of IncI (Gamma)-like plasmids mediated by extended-spectrum β-lactamase gene blaCTX-M-14 as well as gyrA 87 mutation, which had not been reported before. It was noted that IncI (Gamma)-like plasmids were reported in S. Typhimurium for the first time and conjugation could accelerate the spread of antimicrobial resistance gene blaCTX-M-14. These findings on the epidemic, antimicrobial resistance, and phylogenomic characterization for S. Typhimurium provide valuable insights into its potential risk to public health and also the basis for AMR prevention and control strategies in Shanghai in the future.
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  • 文章类型: Journal Article
    评估COVID-19大流行对新生儿败血症流行病学的影响以及所涉及病原体的抗生素耐药性。
    这项回顾性队列研究分析了2016年1月至2022年12月在华东地区某三级儿童医院新生儿科诊断为文化证实的败血症的婴儿。我们比较了大流行前I期(2016-2019年)和COVID-19大流行II期(2020-2022年)新生儿败血症病例的临床和微生物学特征。
    共纳入了507名患有525次败血症的婴儿,第一阶段343集,第二阶段182集。早发性败血症(EOS)的发生率在II期期间显着降低(p<0.05)。与第一阶段相比,第二阶段的婴儿的胎龄和出生体重较低。临床症状,如斑驳的皮肤,严重贫血,血小板减少症在II期更为普遍,并发症发生率较高。值得注意的是,坏死性小肠结肠炎(NEC)(p<0.05)和脑膜炎(p<0.1)在II期发生频率更高。大肠杆菌(E.大肠杆菌)和肺炎克雷伯菌(K.肺炎)是从死亡婴儿和并发症病例中分离出的主要病原体。在II期观察到肺炎克雷伯菌比例显着下降,大肠杆菌和肺炎克雷伯菌的抗生素耐药性增加。COVID-19大流行期(II期)被确定为新生儿败血症婴儿并发症的独立危险因素。
    COVID-19大流行应对措施与EOS下降、新生儿败血症并发症和抗生素耐药性增加相关。
    UNASSIGNED: To assess the effects of COVID-19 pandemic on the epidemiology of neonatal sepsis and the antibiotic resistance profiles of pathogens involved.
    UNASSIGNED: This retrospective cohort study analyzed infants diagnosed with culture-proven sepsis at the neonatal department of a tertiary children\'s hospital in East China from January 2016 to December 2022. We compared the clinical and microbiological characteristics of neonatal sepsis cases between the pre-pandemic Phase I (2016-2019) and during the COVID-19 pandemic Phase II (2020-2022).
    UNASSIGNED: A total of 507 infants with 525 sepsis episodes were included, with 343 episodes in Phase I and 182 in Phase II. The incidence of early-onset sepsis (EOS) was significantly lower during Phase II (p < 0.05). Infants in Phase II had lower gestational ages and birth weights compared to Phase I. Clinical signs such as mottled skin, severe anemia, thrombocytopenia were more prevalent in Phase II, alongside a higher incidence of complications. Notably, necrotizing enterocolitis (NEC) (p < 0.05) and meningitis (p < 0.1) occurred more frequently during Phase II. Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) were the predominant pathogens isolated from infants of death and cases with complications. A significant decrease in the proportion of K. pneumoniae was observed in Phase II, alongside increased antibiotic resistance in both E. coli and K. pneumoniae. The period of the COVID-19 pandemic (Phase II) was identified as an independent risk factor for complications in infants with neonatal sepsis.
    UNASSIGNED: COVID-19 pandemic response measures correlated with a decrease in EOS and an increase in neonatal sepsis complications and antibiotic resistance.
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  • 文章类型: Journal Article
    背景:侵袭性肺炎球菌病(IPD)是全世界儿童的重大健康问题。在这项研究中,我们的目的是分析临床特征,抗生素耐药性,杭州IPD患者预后不良的风险变量。
    方法:2010年至2018年,使用儿科重症监护(PIC)数据库进行了一项回顾性单中心研究。临床特点,实验室数据,抗菌素耐药性,并系统分析重症监护病房(ICU)IPD患者院内死亡和脓毒症的危险因素.
    结果:共178例IPD患者纳入研究。大多数IPD儿童为2-10岁。肺炎链球菌的耐药性试验显示对红霉素的高耐药性,四环素和复方磺胺甲恶唑(SMZ-Co)。所有分离株对万古霉素敏感,利奈唑胺,莫西沙星,泰利霉素,氧氟沙星,和左氧氟沙星.IPD患者可能会出现不良结果,包括死亡和败血症.住院死亡率为3.93%,34.27%的患者患有脓毒症。温度(OR3.80,95%CI1.62-8.87;P=0.0021),动脉血氧分压(PaO2)(OR0.99,95%CI0.98-1.00;P=0.0266),白蛋白(OR0.89,95%CI0.80-0.99;P=0.0329)是IPD患儿脓毒症的独立危险因素。
    结论:小儿IPD在中国值得关注。适当的监测和抗生素选择对于管理耐药菌株至关重要。早期识别具有危险因素的高危个体有助于制定适当的治疗策略。
    BACKGROUND: Invasive pneumococcal disease (IPD) is a significant health concern in children worldwide. In this study, we aimed to analyze the clinical features, antibiotic resistance, and risk variables for poor outcomes in patients with IPD in Hangzhou.
    METHODS: A retrospective single-centre study was performed using the pediatric intensive care (PIC) database from 2010 to 2018. The clinical characteristics, laboratory data, antimicrobial resistance, and risk factors for in-hospital mortality and sepsis in patients with IPD in intensive care units (ICUs) were analyzed systematically.
    RESULTS: A total of 178 IPD patients were included in the study. The majority of the IPD children were 2-10 years old. Antimicrobial resistance tests of S. pneumoniae isolates revealed high resistance to erythromycin, tetracycline and compound sulfamethoxazole (SMZ-Co). All the isolates were sensitive to vancomycin, linezolid, moxifloxacin, telithromycin, ofloxacin, and levofloxacin. IPD patients may experience poor outcomes, including death and sepsis. The in-hospital mortality was 3.93%, and 34.27% of patients suffered from sepsis. Temperature (OR 3.80, 95% CI 1.62-8.87; P = 0.0021), Partial Pressure of Oxygen in Arterial Blood (PaO2) (OR 0.99, 95% CI 0.98-1.00; P = 0.0266), and albumin (OR 0.89, 95% CI 0.80-0.99; P = 0.0329) were found to be independent risk factors for sepsis in children with IPD.
    CONCLUSIONS: Pediatric IPD deserves attention in China. Appropriate surveillance and antibiotic selection are crucial in managing resistant strains. Early identification of high-risk individuals with risk factors contributes to the development of appropriate treatment strategies.
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  • 文章类型: Journal Article
    由细菌引起的传染病,病毒,和真菌病原体带来了重大的全球健康挑战。抗生素耐药性的迅速出现加剧了这个问题,导致有效抗生素越来越稀缺的情况。传统的抗生素开发策略被证明不足以抵抗微生物抗性的快速进化。因此,迫切需要开发具有不同于现有抗生素的机制的新型抗菌策略.纳米酶,是基于纳米酶的抗菌剂,模拟溶酶体酶在先天免疫细胞中的催化作用,以杀死感染性病原体。这篇综述加强了纳米酶的概念,并对潜在的抗微生物候选物的最新研究进展进行了全面总结。最初,纳米酶根据它们的活性进行分类,模拟氧化还原酶样或水解酶样功能,从而突出了他们在对抗抗生素耐药性方面的优越机制。然后,本文讨论了纳米酶在治疗细菌方面的进展,病毒,和真菌感染,证实了它们作为新型抗菌候选药物的潜力。基于纳米酶的产品的翻译潜力,包括水凝胶,纳米机器人,喷雾剂,绷带,面具,和防护服,也考虑到了。最后,探讨了纳米酶相关产品的当前挑战和未来前景,强调未来应用纳米酶的设计和抗菌能力。本文受版权保护。保留所有权利。
    Infectious diseases caused by bacterial, viral, and fungal pathogens present significant global health challenges. The rapid emergence of antimicrobial resistance exacerbates this issue, leading to a scenario where effective antibiotics are increasingly scarce. Traditional antibiotic development strategies are proving inadequate against the swift evolution of microbial resistance. Therefore, there is an urgent need to develop novel antimicrobial strategies with mechanisms distinct from those of existing antibiotics. Nanozybiotics, which are nanozyme-based antimicrobials, mimic the catalytic action of lysosomal enzymes in innate immune cells to kill infectious pathogens. This review reinforces the concept of nanozymes and provides a comprehensive summary of recent research advancements on potential antimicrobial candidates. Initially, nanozybiotics are categorized based on their activities, mimicking either oxidoreductase-like or hydrolase-like functions, thereby highlighting their superior mechanisms in combating antimicrobial resistance. The review then discusses the progress of nanozybiotics in treating bacterial, viral, and fungal infections, confirming their potential as novel antimicrobial candidates. The translational potential of nanozybiotic-based products, including hydrogels, nanorobots, sprays, bandages, masks, and protective clothing, is also considered. Finally, the current challenges and future prospects of nanozybiotic-related products are explored, emphasizing the design and antimicrobial capabilities of nanozybiotics for future applications.
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  • 文章类型: Journal Article
    抗菌素耐药性(AMR)破坏了联合国可持续发展目标的良好健康和福祉。已知抗生素会加剧AMR,但是非抗生素抗生素,例如季铵化合物(QAC),现在正在成为AMR的另一个重要驱动力。然而,由于化学结构和抗菌活性的模糊性,评估QAC在复杂环境基质中的AMR风险仍然具有挑战性。通过机器学习预测和高分辨率质谱分析,编制了工业化学品清单中的抗菌QAC(n=856)清单,它导致了沉积物中50种结构多样的抗菌QAC的鉴定,包括传统的烃基化合物和带有额外官能团的新亚类,比如胆碱,酯,甜菜碱,芳基醚,还有吡啶.城市废水,水产养殖,和医院出院是影响河口沉积物QAC分布规律的主要因素。毒性单位计算和宏基因组分析显示,这些QAC可以通过交叉和共抗性影响抗生素抗性基因(特别是磺酰胺抗性基因)。影响AMR的潜力与其环境持久性有关。这些结果表明,控制源头,防止共同使用QAC和磺胺类药物,优先控制高持久性分子将导致全球管理和可持续使用QAC。
    Antimicrobial resistance (AMR) undermines the United Nations Sustainable Development Goals of good health and well-being. Antibiotics are known to exacerbate AMR, but nonantibiotic antimicrobials, such as quaternary ammonium compounds (QACs), are now emerging as another significant driver of AMR. However, assessing the AMR risks of QACs in complex environmental matrices remains challenging due to the ambiguity in their chemical structures and antibacterial activity. By machine learning prediction and high-resolution mass spectrometric analysis, a list of antibacterial QACs (n = 856) from industrial chemical inventories is compiled, and it leads to the identification of 50 structurally diverse antibacterial QACs in sediments, including traditional hydrocarbon-based compounds and new subclasses that bear additional functional groups, such as choline, ester, betaine, aryl ether, and pyridine. Urban wastewater, aquaculture, and hospital discharges are the main factors influencing QAC distribution patterns in estuarine sediments. Toxic unit calculations and metagenomic analysis revealed that these QACs can influence antibiotic resistance genes (particularly sulfonamide resistance genes) through cross- and coresistances. The potential to influence the AMR is related to their environmental persistence. These results suggest that controlling the source, preventing the co-use of QACs and sulfonamides, and prioritizing control of highly persistent molecules will lead to global stewardship and sustainable use of QACs.
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