Opportunistic pathogen

机会性病原体
  • 文章类型: Case Reports
    此病例报告描述了一名因重症肺炎住院的女婴的病例。在治疗过程中,各种抗生素用于治疗和预防进一步的感染。孩子的身体状况很虚弱,合并神经母细胞瘤,副肿瘤综合征,免疫功能低下,导致酪氨酸梭菌感染。由于预后不良,最终放弃了治疗。本研究旨在通过媒介,染色,电子显微镜观察,16srRNA和高通量测序研究了形态学特征,染色属性,电子显微镜形态学,抗生素耐药性,和酪氨酸酶的基因组特征。本研究旨在为临床检验人员进行细菌鉴定研究提供数据参考,为临床医生的诊断和治疗提供相关帮助。
    This case report describes the case of a female infant hospitalized for severe pneumonia. During the treatment process, various antibiotics are used to treat and prevent further infection. The child had a weak physical condition, combined with neuroblastoma, paraneoplastic syndrome, and low immune function, leading to Tsukamurella tyrosinosolvens infection. The treatment was eventually abandoned owing to poor prognosis. This study aims to through the medium, dyeing, electron microscope observation, 16s rRNA and high-throughput sequencing investigated the morphological characteristics, staining properties, electron microscope morphology, antibiotic resistance, and genomic characteristics of Tsukamurella tyrosinosolvens. The aim of the study is to provide data reference for clinical laboratory staff in bacteria identification research, and to provide relevant help for clinicians in diagnosis and treatment.
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  • 文章类型: Journal Article
    背景:人口腔和鼻腔可以充当能够引起急性感染的机会病原体的储库。这些微生物无源地定植于人类口腔和鼻腔,有助于通过环境在人群中传播。它们通常具有临床上显著的抗生素抗性基因。在这些机会性病原体中,克雷伯菌属是一个值得注意的例子,其成员经常与医院感染和多药耐药性有关。与许多定殖的机会病原体一样,影响克雷伯氏菌在健康和患病个体中传播的基本传播因素仍不清楚。
    结果:这里,我们通过研究口腔和鼻腔克雷伯菌物种在体外饥饿条件下超越其天然微生物群落成员的能力,探索了一种可能的解释。这可能类似于医院外部环境或机械呼吸机的微环境。当健康人体口腔或鼻腔样本中存在肺炎克雷伯菌和产气克雷伯菌时,在饥饿条件下,细菌群落组成发生了急剧变化,通常富含克雷伯菌属。此外,将肺炎克雷伯菌外源引入缺乏肺炎克雷伯菌的本地微生物群落,即使在低接种量下,导致在饥饿下反复富集。与微生物组的其他成员相比,在这些经历饥饿的社区内对肺炎克雷伯菌的精确监测表明快速的初始生长和延长的生存能力。从健康个体口腔和鼻腔分离的肺炎克雷伯菌菌株也表现出对多种抗生素的抗性,并且在遗传上与临床和肠道分离株相似。此外,我们发现在没有克雷伯菌属的情况下,其他研究不足的机会病原体,如肽链球菌,在饥饿条件下相对丰度增加。
    结论:我们的研究结果建立了一个环境和微生物群落环境,允许克雷伯氏菌和其他机会性病原体的富集。克雷伯菌的富集可能取决于其迅速超越微生物组其他成员的能力。与其他共生细菌竞争并在恶劣环境条件下持续存在的能力可能是有助于在共生和致病环境中增强传播的重要因素。视频摘要。
    BACKGROUND: The human oral and nasal cavities can act as reservoirs for opportunistic pathogens capable of causing acute infection. These microbes asymptomatically colonize the human oral and nasal cavities which facilitates transmission within human populations via the environment, and they routinely possess clinically significant antibiotic resistance genes. Among these opportunistic pathogens, the Klebsiella genus stands out as a notable example, with its members frequently linked to nosocomial infections and multidrug resistance. As with many colonizing opportunistic pathogens, the essential transmission factors influencing the spread of Klebsiella species among both healthy and diseased individuals remain unclear.
    RESULTS: Here, we explored a possible explanation by investigating the ability of oral and nasal Klebsiella species to outcompete their native microbial community members under in vitro starvation conditions, which could be analogous to external hospital environments or the microenvironment of mechanical ventilators. When K. pneumoniae and K. aerogenes were present within a healthy human oral or nasal sample, the bacterial community composition shifted dramatically under starvation conditions and typically became enriched in Klebsiella species. Furthermore, introducing K. pneumoniae exogenously into a native microbial community lacking K. pneumoniae, even at low inoculum, led to repeated enrichment under starvation. Precise monitoring of K. pneumoniae within these communities undergoing starvation indicated rapid initial growth and prolonged viability compared to other members of the microbiome. K. pneumoniae strains isolated from healthy individuals\' oral and nasal cavities also exhibited resistance to multiple classes of antibiotics and were genetically similar to clinical and gut isolates. In addition, we found that in the absence of Klebsiella species, other understudied opportunistic pathogens, such as Peptostreptococcus, increased in relative abundance under starvation conditions.
    CONCLUSIONS: Our findings establish an environmental and microbiome community circumstance that allows for the enrichment of Klebsiella species and other opportunistic pathogens. Klebsiella\'s enrichment may hinge on its ability to quickly outgrow other members of the microbiome. The ability to outcompete other commensal bacteria and to persist under harsh environmental conditions could be an important factor that contributes to enhanced transmission in both commensal and pathogenic contexts. Video Abstract.
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  • 文章类型: Journal Article
    柠檬酸杆菌koseri(C.koseri)是革兰氏阴性的,能动,属于肠杆菌科的非孢子形成兼性厌氧杆菌。C.koseri通常利用柠檬酸盐作为唯一的碳源并且构成人和动物的正常胃肠菌群的一部分。作为一种机会性病原体,C.koseri感染主要在新生儿中观察到,老年人,和免疫受损的宿主。C.koseri已成为新生儿脑膜炎和脑脓肿的主要病因之一。近年来,据报道,由C.koseri引起的严重感染的成人病例越来越多。这里,我们首次报道一例重症哮喘患者并发C.koseri腹腔感染的临床病例,并对相关文献进行简要回顾.有了这份报告,我们希望提高临床医生对需要长期口服糖皮质激素的哮喘患者并发肠道共生菌感染可能性的认识和警觉性.
    Citrobacter koseri (C. koseri) is a Gram-negative, motile, non-spore-forming facultative anaerobic bacillus belonging to the Enterobacteriaceae family. C. koseri typically utilizes citrate as the sole carbon source and constitutes part of the normal gastrointestinal flora in humans and animals. As an opportunistic pathogen, C. koseri infections are mainly observed in neonates, elderly individuals, and immunocompromised hosts. C. koseri has been one of the main etiological agents of neonatal meningitis and cerebral abscess. In recent years, an increasing number of cases have been reported in adults with severe infections caused by C. koseri. Here, we report for the first time a clinical case of concurrent C. koseri intra-abdominal infection in a patient with severe asthma and provide a brief review of the relevant literature. With this report, we hope to increase awareness and alertness among clinicians to the possibility of concurrent infection of gut commensal bacteria in asthmatic patients requiring long-term oral corticosteroid administration.
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  • 文章类型: Journal Article
    香蕉(Musaspp。)是世界范围内重要的水果和粮食作物。近年来,香蕉鞘腐病已成为香蕉种植的主要问题,造成植物死亡和巨大的经济损失。然而,这种疾病的病原体特征尚未完全表征。Klebsiellavariicola是一种能够定殖不同宿主的多功能细菌,比如植物,人类,昆虫,和动物,并被认为是各种宿主中新兴的病原体。在这项研究中,我们从12个不同的香蕉样品中获得了12个细菌分离株,这些样品在广东和广西两省表现出香蕉鞘腐烂,中国。基于16SrRNA序列的系统发育分析证实,所有12个分离株均为Variicola菌株。我们对这些菌株的基因组进行了测序,与其他测序的K.variicola菌株进行比较基因组分析,并发现这些K.variicola菌株之间的辅助基因含量缺乏一致性。然而,基于K.variicola全基因组的预测揭示了12个致病性K.variicola分离株携带的22个独特的毒力因子。通过对2个品种的健康植物与病菌健康组织内生菌的微生物组和微生物互作网络分析,发现香蕉植物中甲烷杆菌与克雷伯菌呈负向相互作用,而草本菌可能间接抑制甲烷杆菌促进克雷伯菌的生长。这些结果表明,香蕉鞘腐病是由植物内生菌和机会致病菌的不平衡引起的,为本病的研究和控制提供了重要依据。[公式:见正文]版权所有©2023作者(S)。这是在CCBY-NC-ND4.0国际许可证下分发的开放访问文章。
    Banana (Musa spp.) is an important fruit and food crop worldwide. In recent years, banana sheath rot has become a major problem in banana cultivation, causing plant death and substantial economic losses. Nevertheless, the pathogen profile of this disease has not been fully characterized. Klebsiella variicola is a versatile bacterium capable of colonizing different hosts, such as plants, humans, insects, and animals, and is recognized as an emerging pathogen in various hosts. In this study, we obtained 12 bacterial isolates from 12 different banana samples showing banana sheath rot in Guangdong and Guangxi Provinces, China. Phylogenetic analysis based on 16S rRNA sequences confirmed that all 12 isolates were K. variicola strains. We sequenced the genomes of these strains, performed comparative genomic analysis with other sequenced K. variicola strains, and found a lack of consistency in accessory gene content among these K. variicola strains. However, prediction based on the pan-genome of K. variicola revealed 22 unique virulence factors carried by the 12 pathogenic K. variicola isolates. Microbiome and microbial interaction network analysis of endophytes between the healthy tissues of diseased plants and healthy plants of two cultivars showed that Methanobacterium negatively interacts with Klebsiella in banana plants and that Herbaspirillum might indirectly inhibit Methanobacterium to promote Klebsiella growth. These results suggest that banana sheath rot is caused by the imbalance of plant endophytes and opportunistic pathogenic bacteria, providing an important basis for research and control of this disease.[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.
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  • 文章类型: Case Reports
    一名34岁男性出现肺部阴影,在体检期间无症状。患者有甲状腺肿瘤病史。影像学表现:右中叶内侧节结节,病灶内远端支气管部分阻塞。在右上叶前段观察到磨玻璃和炎性结节,以及右肺下叶的慢性炎症变化。肺组织病理学检查提示浸润性腺癌。支气管肺泡灌洗液的形态学检查显示存在Tropherymawhipplei(TW)和诺卡氏菌。尽管已经报道了癌症患者的TW感染,在这种情况下,与诺卡氏菌共感染是一种独特的现象。机会性病原体在免疫受损患者中很常见,但在这种情况下,该患者是一名免疫正常的年轻成年人,并且是TW和诺卡氏菌共感染的早期肿瘤。我们通过成像发现证明了稀有微生物的存在,结合不同染色方法对支气管肺泡灌洗液和肺组织切片进行形态学评价。本研究的目的是通过改进微生物形态学检测来提供患者的早期诊断和治疗。
    A 34-year-old male presented with lung shadow and was asymptomatic during medical examination. The patient had a prior history of thyroid tumors. Imaging manifestation showed a nodule in the medial segment of the right middle lobe, with partial obstruction of the distal bronchus within the lesion. Ground-glass and inflammatory nodules were observed in the anterior segment of the right upper lobe, as well as chronic inflammatory changes in the lower lobe of the right lung. Lung histopathological examination suggested invasive adenocarcinoma. A morphological examination of the bronchoalveolar lavage fluid revealed the presence of Tropheryma whipplei (TW) and Nocardia. Although TW infection has been reported in cancer patients, co-infection with Nocardia is a unique occurrence in this case. Opportunistic pathogens are common in immunocompromised patients but in this case, the patient was a young adult with normal immunity and an early-stage tumor with TW and Nocardia co-infection. We demonstrated the presence of rare microorganisms through imaging findings, combined with different staining methods of bronchoalveolar lavage fluid and lung tissue sections and evaluation of morphological characteristics. The aim of the present study was to provide early diagnosis and treatment of patients by improving microbial morphological detection.
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  • 文章类型: Journal Article
    洋葱伯克霍尔德菌(B.洋葱)是携带囊性纤维化的儿科患者医院感染的新兴病原体。关于洋葱芽孢杆菌感染的临床诊断和治疗研究甚少。这项研究概述了风险因素,抗菌敏感性,旨在提高洋葱芽孢杆菌感染的治疗方法和临床特点。
    对50例不囊性纤维化患儿由洋葱芽孢杆菌引起的感染病例进行了回顾性研究,在厦门大学附属第一医院确诊,从1月1日,2011年12月31日,2021年。
    共有50名儿童感染了洋葱芽孢杆菌,其中68%有潜在的健康状况,如心血管疾病(23.5%),呼吸系统疾病(17.6%),神经系统疾病(14.7%),和肿瘤性疾病(14.7%)。在洋葱芽孢杆菌感染开始时,42名(84%)儿科患者在重症监护病房(ICU),33人(66%)接受气管插管,32(64%)有中心静脉导管(CVC)。此外,医院获得性病例为46例(92%),医疗保健获得的病例为4例(12%)。最常见的感染部位是呼吸道(68%),其次是血液(20%),和泌尿道(12%)。结果表明,百合菌对头孢他啶最敏感(95.65%),其次是甲氧苄啶-磺胺甲恶唑(88.68%),美罗培南(82.98%),头孢吡肟(77.78%),和左氧氟沙星(55.85%)。哌拉西林他唑巴坦的耐药率,米诺环素,氨曲南,头孢哌酮-舒巴坦和头孢曲松均高于55%。38例治愈或好转,八人终止了治疗,四人死亡。
    B洋葱是一种机会性病原体,通常在免疫功能低下的儿科患者中发现,极有可能导致耐药性。根据我们的观察,医院内的洋葱芽孢杆菌感染主要发生在ICU患者中。包括改变流行病学和增加微生物耐药性在内的洋葱芽孢杆菌感染的监测仍然非常重要。用有效的抗生素如头孢他啶治疗,美罗培南,甲氧苄啶-磺胺甲恶唑与良好的预后相关。
    UNASSIGNED: Burkholderia cepacia (B. cepacia) is an emerging pathogen of nosocomial infection in pediatric patient carrying cystic fibrosis. The clinical diagnosis and treatment of B. cepacia infection remains poorly studied. This study outlined the risk factors, antimicrobial susceptibility, and clinical characteristics aiming to improve the treatment of B. cepacia infection.
    UNASSIGNED: A retrospective study was conducted based on the 50 cases infection caused by B. cepacia in children without cystic fibrosis, which were diagnosed in the First Affiliated Hospital of Xiamen University, from January 1st, 2011 to December 31st, 2021.
    UNASSIGNED: A total of 50 children were infected with B. cepacia, of whom 68% had an underlying health condition, such as cardiovascular disease (23.5%), respiratory disease (17.6%), nervous system disease (14.7%), and neoplastic disease (14.7%). At the onset of B. cepacia infection, 42 (84%) pediatric patients were in an intensive care unit (ICU), 33 (66%) underwent endotracheal intubation, and 32 (64%) had a central venous catheter (CVC). In addition, hospital-acquired cases were 46 (92%), and healthcare-acquired cases were 4 (12%). The most common infectious sites of B. cepacia were the respiratory tract (68%), followed by the blood (20%), and the urinary tract (12%). It indicated that B. cepacia was the most sensitive to ceftazidime (95.65%), followed by trimethoprim-sulfamethoxazole (88.68%), meropenem (82.98%), cefepime (77.78%), and levofloxacin (55.85%). The drug resistance rate of piperacillin-tazobactam, minocycline, aztreonam, cefoperazone-sulbactam and ceftriaxone was higher than 55%. 38 cases were cured or improved, eight had treatment terminated, and four died.
    UNASSIGNED: B. cepacia is an opportunistic pathogen normally found in immunocompromised pediatric patients and highly likely to lead to drug resistance. Nosocomial B. cepacia infections occurred mostly in patients in the ICU based on our observations. The surveillance of B. cepacia infections including changing epidemiology and increasing resistance of the microorganism is still very important. Treatment with effective antibiotics such as ceftazidime, meropenem, trimethoprim-sulfamethoxazole is associated with a favorable prognosis.
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  • 文章类型: Journal Article
    抗生素在医学和农业中的广泛使用导致了环境中抗生素抗性微生物和抗生素抗性基因(ARGs)的积累,威胁人类健康和污染环境。杀线虫剂阿维菌素被广泛应用于根结线虫的防治。研究了施用阿维菌素5年对农田病烟根际微生物组及抗病性的影响。充分评估了阿维菌素的环境风险。采用宏基因组方法分析了阿维菌素处理土壤中的抗生素抗性细菌和抗生素抗性基因。抗生素抗性细菌的丰度和分布及其抗生素抗性基因受阿维菌素应用的影响。抗生素抗性变形杆菌在根际土壤中占最高比例(36%),并携带530个ARG。在阿维菌素处理的土壤中富集了携带抗生素抗性基因的机会性人类病原体。阿维菌素的应用增加了许多类型的抗生素抗性基因的数量。基因adeF的相对丰度,巴哈,fush,Ies,阿维菌素处理土壤中的tlrB和tlrB明显大于未处理的对照土壤。在阿维菌素处理的土壤中揭示了不同的抗性机制。抗生素的外排(670ARGs),抗生素灭活(475ARGs),抗生素靶标(267ARGs)的改变是主要的抗性机制。刚性控制阿维菌素的剂量和使用频率等农药可以降低土壤抗生素抗性基因,保护农产品安全和公众健康。总的来说,杀线虫剂阿维菌素富集抗生素抗性细菌和抗生素抗性基因在农田土壤中的应用,应该警惕环境保护。
    The extensive use of antibiotics in medicine and agriculture has resulted in the accumulation of antibiotic-resistant microorganisms and antibiotic resistance genes (ARGs) in environments, which threaten human health and contaminate environment. Nematicide avermectin is widely applied to control root-knot nematodes. The effect of five-years application of avermectin on rhizosphere microbiome and resistome of sick tobacco plants in farmland were investigated in present study. The environmental risks of avermectin was assessed adequately. Metagenomic method was used to analyze antibiotic-resistant bacteria and antibiotic resistance genes in the avermectin-treated soil. The abundance and distribution of antibiotic-resistant bacteria and their antibiotic resistance genes were affected by avermectin application. The antibiotic resistant Proteobacteria occupied the highest percentage (36%) in rhizosphere soil and carried 530 ARGs. Opportunistic human pathogens carrying antibiotic resistance genes were enriched in the avermectin-treated soil. Avermectin application increased the counts of many types of antibiotic resistance genes. The relative abundances of genes adeF, BahA, fusH, ileS, and tlrB in the avermectin-treated soil were significantly greater than in the untreated control soil. Different resistance mechanisms were revealed in the avermectin-treated soil. The efflux of antibiotic (670 ARGs), inactivation of antibiotic (475 ARGs), and alteration of antibiotic target (267 ARGs) were the main resistance mechanisms. Rigid control the avermectin dose and use frequency and other pesticides can decrease soil antibiotic resistance genes and protect agricultural products\' safety and public health. Overall, application of nematicide avermectin enriched antibiotic-resistant bacteria and antibiotic resistance genes in farmland soil, which should be on the alert for environment protection.
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  • 文章类型: Journal Article
    由于动物car体腐烂引起的抗生素抗性污染已成为严重的环境问题。然而,尸体分解的主要代谢产物化合物之间的关系(即,腐胺和尸胺)和抗生素耐药性尚不清楚。为了解决这个问题,水生环境中抗生素抗性基因(ARGs)和微生物群对过量腐胺的反应,基于实验室模拟实验,采用高通量定量PCR和扩增子测序方法对尸胺和两者的混合物进行了研究。我们的结果表明,腐胺和尸胺导致水和沉积物中TC(总碳)和TN(总氮)的增加。在腐胺和尸胺的暴露下,水中可移动遗传元件(MGEs)和大多数ARGs的总丰度高于沉积物。特别是,与对照组相比,腐胺和尸胺引起水和沉积物中微生物群落α多样性的显着降低。尸体和腐胺也显着影响了水和沉积物中的微生物群落结构。此外,腐胺和尸胺导致沉积物中高风险ARGs(如mecA)和机会性病原体(如Delftia)不同程度的增加,促进抗生素耐药菌的流行。总之,我们的发现揭示了car体腐烂的主要代谢产物对微生物组和抗性的影响,为风险评估和污染管理提供参考。
    Contamination of antibiotic resistomes due to animal carcass decay has become a serious environmental concern. However, the relationship between main metabolite compounds of corpse decomposition (i.e., putrescine and cadaverine) and antibiotic resistomes remains unclear. To tackle this issue, the response of antibiotic resistance genes (ARGs) and microbiome in aquatic environment to excess putrescine, cadaverine and a mixture of both based on laboratory simulation experiment was investigated by high-throughput quantitative PCR and amplicon sequencing methods. Our results showed putrescine and cadaverine led to the increasing of TC (total carbon) and TN (total nitrogen) both in water and sediment. Under the exposure of putrescine and cadaverine, the total abundance of mobile genetic elements (MGEs) and most ARGs in water was higher than in sediment. In particular, putrescine and cadaverine caused significantly different decreases in alpha diversity of microbial community in water and sediment compared with the control group. Microbial community structures both in water and sediment were also significantly affected by cadaverine and putrescine. Furthermore, putrescine and cadaverine led to different degrees of increases of high-risk ARGs (like mecA) and opportunistic pathogens (like Delftia) in sediment, promoting the prevalence of antibiotic resistant bacteria. In conclusion, our findings revealed the influences of main metabolites of carcass decay on microbiome and resistomes, providing references for risk assessment and pollution management.
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  • 文章类型: Journal Article
    背景:Delftiaacidovorans在环境中广泛分布,具有促进植物生长和降解有机污染物的潜力。然而,它也是人类的机会病原体,许多报道表明,D.acidovorans对氨基糖苷和多粘菌素具有很强的抗性。
    目的:这项工作的目的是揭示一种新的条件致病菌株D中的抗生素耐药基因和致病基因。从新疆维吾尔自治区辐射污染土壤中分离出的酸果类B804,中国。
    方法:根据Kirby-Bauer圆盘扩散法进行抗生素耐药性测试,并通过临床和实验室标准研究所指南的标准进行评估。在上海MajorbioBiopharmTechnologyCo.的PacBioRSII和IlluminaHiSeq4000平台上对D.acidovoransB804的基因组进行了测序。有限公司(上海,中国)。
    结果:实验证实了D.acidovoransB804的多药耐药表型,并对其基因组进行了测序。酸曲霉B804基因组的总大小为6,661,314bp,GC含量为66.73%。预测了403个与抗生素抗性相关的基因。同时,还预测了89个致病基因,其中17个基因可能会导致人类疾病,如感染和沙门氏菌病。
    结论:该基因组信息可用作比较基因组研究的参考序列。本研究结果提供了有关D.acidovorans的发病机制和耐药机制的更多见解,这将是有意义的开发更有效的治疗对D.acidovorans相关的疾病。
    BACKGROUND: Delftia acidovorans is distributed widely in the environment and has the potential to promote the growth of plants and degrade organic pollutants. However, it is also an opportunistic pathogen for human and many reports demonstrated that D. acidovorans has strong resistance to aminoglycosides and polymyxins.
    OBJECTIVE: The aim of this work was to reveal the antibiotic resistance genes and pathogenic genes in a novel conditional pathogenic strain-D. acidovorans B804, which was isolated from the radiation-polluted soil from Xinjiang Uyghur Autonomous Region, China.
    METHODS: The antibiotic resistance test was performed according to the Kirby-Bauer disk diffusion method and evaluated by the standards of the Clinical and Laboratory Standards Institute guidelines. The genome of D. acidovorans B804 was sequenced by a PacBio RS II and Illumina HiSeq 4000 platform in Shanghai Majorbio Biopharm Technology Co., Ltd. (Shanghai, China).
    RESULTS: The multidrug resistance phenotypes of D. acidovorans B804 was experimentally confirmed and its genome was sequenced. The total size of D. acidovorans B804 genome was 6,661,314 bp with a GC content of 66.73%. 403 genes associated with antibiotic resistances were predicted. Meanwhile, 89 pathogenic genes were also predicted and 17 of these genes might be capable of causing diseases to human, such as infections and salmonellosis.
    CONCLUSIONS: This genomic information can be used as a reference sequence for comparative genomic studies. The results provided more insights regarding the pathogenesis and drug resistance mechanism of D. acidovorans, which will be meaningful for developing more effective therapies toward D. acidovorans-related diseases.
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  • 文章类型: Journal Article
    抗生素的过度使用会导致耐药性的增加。尤其是,多药耐药鲍曼不动杆菌成为医院感染的主要原因,死亡率高.鲍曼不动杆菌的耐药性很大程度上归因于其生物膜。减轻耐药负担,开发了抗毒力信号策略。通过特异性干扰细菌识别建立感染所需的宿主信号的能力,细菌在宿主中的定殖能力较低。在本文中,合成了39个N-酰基-2-氨基嘧啶衍生物并测试了它们的生物膜抑制功效。筛选结果表明,一些类似物(3ac,8d)有效抑制鲍曼不动杆菌的生物膜形成(IC50低至3.8μM),激光共聚焦结果和胞外多糖抑制试验进一步证明了生物膜抑制能力。进一步的运动性测试显示我们的化合物是群体感应抑制剂。此外,化合物3ac和8d与不同抗生素的协同作用提示其潜在的临床意义,PLGA涂层后的长期生物膜抑制试验进一步增强。最后,我们还通过细胞毒性试验研究了化合物的安全性。
    The overuse of antibiotics will led to the increase of drug resistance. Especially, the multidrug-resistant A. baumannii became the leading cause of nosocomial infections with high rates of morbimortality. The drug resistance of A. baumannii is greatly attributed to its biofilm. To alleviate the burden of drug resistance, the anti-virulence signaling strategies was developed. By specifically interfering with the ability of the bacteria to recognize host signals that are needed to establish infection, the bacteria are less able to colonize the host. In this paper, 39 N-acyl-2-aminopyrimidine derivatives were synthesized and tested for their biofilm inhibition efficacy. The screening results reveal that some of the analogues (3ac, 8d) efficiently inhibited the biofilm formation of A. baumannii (IC50 as low as 3.8 μM), and the biofilm inhibition ability was further demonstrated with laser confocal results and extracellular polysaccharides inhibition test. Further motility test reveals our compounds are quorum sensing inhibitors. Besides, the synergistic effect of compounds 3ac and 8d with different antibiotics suggest its potential clinical significance, which was further enhanced by the long time biofilm inhibition test after coating with PLGA. Finally, we also look into the safety of the compounds with cytotoxicity assay.
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