parasite

寄生虫
  • 文章类型: Journal Article
    大多数宿主-寄生虫关联是通过宿主利用的系统发育保守能力来解释的,因此,寄生虫在远亲宿主之间的转换是罕见的。在这里,我们报告了从侵入性囊虫Mnemimopsisleidyi到两个镰刀虫宿主的洞穴海葵Edwardsiellacarnea寄生溢出的第一个证据:本地地中海桶水母Rhizostomapulmo和侵入性印度太平洋游牧水母Rhopilemanomadica,从东地中海收集。使用线粒体16S和核18SrRNA基因的分子分析鉴定了在这些水母中发现的爱德华氏杆菌。总的来说,在触手上发现了93个扁平虫,口腔手臂,在镰刀的胃血管管内,而在共现的眼窝中未观察到感染。DNA元编码方法表明Edwardsiellasp。在东地中海中游浮游动物中,恰逢水母在该地区开花。我们的发现表明,基于共同的功能而不是进化史,爱德华氏菌与各种凝胶状宿主之间存在非特异性寄生关系。可能是由水母开花引起的宿主可用性变化所驱动的。这种溢出效应引发了有关寄生虫对本地和侵入性镰刀虫宿主的生态影响以及Edwardsiella在控制其种群中的潜在作用的疑问。
    Most host-parasite associations are explained by phylogenetically conservative capabilities for host utilization, and therefore parasite switches between distantly related hosts are rare. Here we report the first evidence of a parasitic spillover of the burrowing sea anemone Edwardsiella carnea from the invasive ctenophore Mnemiopsis leidyi to two scyphozoan hosts: the native Mediterranean barrel jellyfish Rhizostoma pulmo and the invasive Indo-Pacific nomad jellyfish Rhopilema nomadica, collected from the Eastern Mediterranean Sea. Edwardsiella carnea planulae found in these jellyfish were identified using molecular analyses of the mitochondrial 16S and nuclear 18S rRNA genes. Overall, 93 planulae were found on tentacles, oral arms, and inside of the gastrovascular canals of the scyphomedusae, whereas no infection was observed in co-occurring ctenophores. DNA metabarcoding approach indicated seasonal presence of Edwardsiella sp. in the Eastern Mediterranean mesozooplankton, coinciding with jellyfish blooms in the region. Our findings suggest a non-specific parasitic relationship between Edwardsiella carnea and various gelatinous hosts based on shared functionality rather than evolutionary history, potentially driven by shifts in host availability due to jellyfish blooms. This spillover raises questions about the ecological impacts of parasitism on native and invasive scyphozoan hosts and the potential role of Edwardsiella in controlling their populations.
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  • 文章类型: Journal Article
    背景:巴西弓形虫病患病率很高。然而,在不同环境中弓形虫的血清阳性率比较方面存在差距,特别是农村和城市地区的怀孕居民。
    方法:比较城市孕妇弓形虫IgG和IgM的患病率,城郊,和巴西东南部一个城市的农村聚居区。有关年龄和居住地区的信息是从2015年1月到2022年12月编制的。采用Logistic回归分析评估年龄和居住地为危险因素。
    结果:共记录了1614次检查,显示54.0%的血清阳性,农村居民区最高(61.1%),其次是城市周边地区(55.9%),市区最低(49.2%)。
    结论:农村地区怀孕居民中IgG和IgM的高患病率,城郊,和城市地区强调了所获得的结果对于加强旨在预防弓形虫病的孕产妇健康计划的重要性,不管他们的住所。
    BACKGROUND: Brazil has a high prevalence of toxoplasmosis. However, there is a gap in comparing seroprevalence for Toxoplasma gondii across different environments, particularly among pregnant residents of rural and urban areas.
    METHODS: The prevalence of IgG and IgM for T. gondii was compared among pregnant residents of the urban, peri-urban, and rural settlement areas in a municipality in southeastern Brazil. Information regarding age and area of residence was compiled from January 2015 to December 2022. Logistic regression analysis was used to assess the age and area of residence as risk factors.
    RESULTS: A total of 1614 examinations were recorded, revealing 54.0% seropositivity, which was highest in the rural settlement (61.1%), followed by the peri-urban area (55.9%), and lowest in the urban area (49.2%).
    CONCLUSIONS: The high prevalence of IgG and presence of IgM in pregnant residents of rural, peri-urban, and urban areas highlights the significance of the results obtained for strengthening maternal health programs aimed at preventing toxoplasmosis, regardless of their residence.
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  • 文章类型: Journal Article
    在Mazatlán附近的毛鳍仰望Selenebrevoortii(Gill)(Carangidae)的g上发现了caligid足类动物(Siphonostomatoida)的标本,锡那罗亚州(墨西哥西北部)。这种材料代表了一种新的Caligus,C.selenecolasp.11月。,并被分配到潜体物种组。在这个群体中,只有C.kapuhiliLewis,1967年,C.laticaudusShiino,1960年,C.macrurusHeller,1865年,和C.selenecolasp.11月。,已经被描述为在腿1的第二外足节段上具有减小的外脊柱1。这四个物种可以很容易地通过腹部的相对长度分开,以及雌性maxilliped的粘液区是否存在过程,胸骨furca,后期过程,和基部触角段上的旋状突。对新物种进行了全面描述,并对CaritustoliiRangnekar发表了一些评论,1984.
    Specimens of a caligid copepod (Siphonostomatoida) were found on the gills of the hairfin lookdown Selenebrevoortii (Gill) (Carangidae) from off Mazatlán, Sinaloa (north-western Mexico). This material represents a new species of Caligus, C.selenecola sp. nov., and is assigned to the diaphanus species group. Within this group, only C.kapuhili Lewis, 1967, C.laticaudus Shiino, 1960, C.macrurus Heller, 1865, and C.selenecola sp. nov., have been described with a reduced outer spine 1 on the second exopodal segment of leg 1. These four species can be readily separated by the relative length of the abdomen, and the presence/absence of a process on the myxal area of the female maxilliped, the sternal furca, the postantennal process, and the spiniform process on the basal antennary segment. A full description of the new species is given with some comments on Caritustolii Rangnekar, 1984.
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  • 文章类型: Journal Article
    人类的寄生吸虫,血吸虫与家畜寄生虫牛在实验室杂交,但自然界中杂交的程度尚不清楚。我们分析了来自18个非洲国家的162个样本中的3460万个单核苷酸变异,揭示了北部和南部嗜血杆菌之间的明显遗传不连续性。我们没有发现最近杂交的证据。相反,数据揭示了在北部S.hematomium种群中发生的257-879代以前的混合事件。15个基因渗入的牛链球菌基因正在接近固定,其中4个基因可能驱动适应。我们确定了19个对基因渗入具有抗性的区域;这些在性染色体上富集。这些结果(I)证明了这些物种之间基因流动的强大障碍,(ii)表明杂交可能不如目前设想的那样普遍,但是(iii)揭示了医学和兽医重要的血吸虫之间种间杂交的深远基因组后果。
    The human parasitic fluke, Schistosoma haematobium hybridizes with the livestock parasite S. bovis in the laboratory, but the extent of hybridization in nature is unclear. We analyzed 34.6 million single nucleotide variants in 162 samples from 18 African countries, revealing a sharp genetic discontinuity between northern and southern S. haematobium. We found no evidence for recent hybridization. Instead the data reveal admixture events that occurred 257-879 generations ago in northern S. haematobium populations. Fifteen introgressed S. bovis genes are approaching fixation in northern S. haematobium with four genes potentially driving adaptation. We identified 19 regions that were resistant to introgression; these were enriched on the sex chromosomes. These results (i) demonstrate strong barriers to gene flow between these species, (ii) indicate that hybridization may be less common than currently envisaged, but (iii) reveal profound genomic consequences of interspecific hybridization between schistosomes of medical and veterinary importance.
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  • 文章类型: Journal Article
    基因组分析显示,包括疟疾寄生虫在内的实验室维持的微生物受到广泛污染,结核分枝杆菌和沙门氏菌。这里,我们提供了实验室血吸虫寄生虫种群最近受到污染的直接证据,我们研究了它的基因组后果。巴西曼氏血吸虫种群SmBRE具有几种独特的表型,传染性差,减少孢子囊数量,在中间蜗牛宿主中,低水平的子囊脱落和低毒力,脊椎动物啮齿动物宿主的蠕虫负担低,繁殖力低。2021年,我们观察到SmBRE寄生虫表型的快速变化,子囊的产量增加了10倍,蠕虫负担增加了4倍。
    为了确定这些变化的潜在基因组原因,我们对2015年至2023年期间寄生虫维持期间收集的SmBRE成虫池进行了测序。我们还对与SmBRE一起维持的另一个寄生虫种群(SmLE)进行了测序,没有表型变化。
    虽然SmLE等位基因频率在八年期间保持稳定,我们在2021年7月至2023年2月期间观察到SmBRE基因组中等位基因频率的突然变化,这与实验室污染的预期一致.(i)在2021年9月至10月之间,SmBRE群体中的SmLE特异性等位基因在整个基因组中从0上升到41-46%,记录了污染事件的时间和程度。(二)污染后,强选择(s=〜0.23)促使用高适合度SmLE等位基因替代低适合度SmBRE。(iii)等位基因频率在整个基因组中迅速变化,除了4号染色体上SmBRE等位基因保持高频率的区域。
    在这种情况下,我们能够检测到污染,因为SmBRE显示出独特的表型。然而,表型相似的寄生虫可能会错过这一点.这些结果为追踪寄生虫种群身份的重要性提供了警示,但也展示了一种简单的方法来监测人群内的变化,使用合并人群样本的分子谱分析来表征固定的单核苷酸多态性。我们还表明,即使在没有污染的情况下,遗传漂移也会导致连续变化,导致保存在不同实验室(或在不同时间从同一实验室取样)的寄生虫发散。
    UNASSIGNED: Genomic analysis has revealed extensive contamination among laboratory-maintained microbes including malaria parasites, Mycobacterium tuberculosis and Salmonella spp. Here, we provide direct evidence for recent contamination of a laboratory schistosome parasite population, and we investigate its genomic consequences. The Brazilian Schistosoma mansoni population SmBRE has several distinctive phenotypes, showing poor infectivity, reduced sporocysts number, low levels of cercarial shedding and low virulence in the intermediate snail host, and low worm burden and low fecundity in the vertebrate rodent host. In 2021 we observed a rapid change in SmBRE parasite phenotypes, with a ~10x increase in cercarial production and ~4x increase in worm burden.
    UNASSIGNED: To determine the underlying genomic cause of these changes, we sequenced pools of SmBRE adults collected during parasite maintenance between 2015 and 2023. We also sequenced another parasite population (SmLE) maintained alongside SmBRE without phenotypic changes.
    UNASSIGNED: While SmLE allele frequencies remained stable over the eight-year period, we observed sudden changes in allele frequency across the genome in SmBRE between July 2021 and February 2023, consistent with expectations of laboratory contamination. (i) SmLE-specific alleles rose in the SmBRE population from 0 to 41-46% across the genome between September and October 2021, documenting the timing and magnitude of the contamination event. (ii) After contamination, strong selection (s = ~0.23) drove replacement of low fitness SmBRE with high fitness SmLE alleles. (iii) Allele frequency changed rapidly across the whole genome, except for a region on chromosome 4 where SmBRE alleles remained at high frequency.
    UNASSIGNED: We were able to detect contamination in this case because SmBRE shows distinctive phenotypes. However, this would likely have been missed with phenotypically similar parasites. These results provide a cautionary tale about the importance of tracking the identity of parasite populations, but also showcase a simple approach to monitor changes within populations using molecular profiling of pooled population samples to characterize fixed single nucleotide polymorphisms. We also show that genetic drift results in continuous change even in the absence of contamination, causing parasites maintained in different labs (or sampled from the same lab at different times) to diverge.
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  • 文章类型: Journal Article
    沿着Ase河的三个站,尼日利亚三角洲州提供了水和85个鱼类样本,并对其进行了分析。根据已建立的方案测量和检查鱼的体内寄生虫。所调查的所有水质参数均在WHO可接受的地表水范围内。各站理化参数变异无统计学意义(p>0.05)。鱼体构象指数与克拉丽亚的寄生虫患病率呈正相关,杂种龙吉菲利斯,ParachanaAfricana,甘特利.甘特利.和Denticeps俱乐部。寄生虫的总体患病率为63.53%,其中最丰富的寄生虫是Trichodinamutabillis。寄生虫对胃肠道有好感,有307人的高发生率。1、2和3站有326、213和259个寄生虫,分别,总共检测到798种寄生虫。P.laevis不在第1站。在第2站和第3站发现了所有寄生虫。统计上,所有站点的患病率均存在显着差异(p<0.05)。1站和3站的T.mutabillis和R.congolensis的相关性指数与水质浓度呈正相关(p<0.05)。然而,1站和3站的水状况对P.laevis产生了有害影响。T.mutabillis与所有三个站的物理化学水质保持高度正相关。第3站的Shannon-Weiner指数(H=1.337)表明寄生虫更加多样化。PCA和生物多样性指数使我们能够理解寄生虫-宿主-环境系统如何相互作用。
    Three stations along the Ase River, Delta State Nigeria provided water and 85 fish samples which were analyzed. The fish were measured and examined for endoparasites according to established protocol. All water quality parameters investigated were within the WHO-acceptable values for surface waters. Station variation of physicochemical parameters was not statistically significant (p > 0.05). Fish body conformation indices positively correlated with the prevalence of parasites in Clarias gariepinus, Heterobranchus longifilis, Parachana africana, Chromidotilapia guntheri guntherii, and Denticeps clupeodes. The overall parasite prevalence of 63.53% was established with the most abundant parasite being Trichodina mutabillis. The parasites had a predilection for the gastrointestinal tract with a high occurrence of 307 individuals. Stations 1, 2, and 3 had 326, 213, and 259 parasites, respectively, out of a total of 798 parasites detected. P. laevis was absent in station 1. All parasites were found in stations 2 and 3. Statistically, there was a significant difference (p < 0.05) in the prevalence in all stations. The correlation index of T. mutabillis and R. congolensis in stations 1 and 3 was positively strong (p < 0.05) with the concentrations of water quality. However, water conditions in stations 1 and 3 had a deleterious impact on P. laevis. T. mutabillis maintained a high positive correlation with physicochemical water quality in all three stations. Shannon-Weiner\'s index in station 3 (H = 1.337) shows that the parasites were more diverse. PCA and biodiversity indices have enabled us to comprehend how parasite-host-environment systems interact.
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  • 文章类型: Journal Article
    渔业在水生生态系统中起着至关重要的作用,具有生态和经济重要性的资源。测量寄生虫的患病率对于评估这些鱼类的健康和福祉是必要的。在锡斯坦地区,这项研究试图估计plerococoridligulatelinalis感染的患病率和强度(L.肠)在七个鱼类中,并确定诸如鱼类体重等因素,季节性,以及可能影响感染率的捕鱼地点。在整个四个季节中,在Sistan地区获得了来自七个物种的2800条鱼。来自三个重量类别的鱼样品(<200gr,200-400gr,400gr<)进行了寄生虫学检查。在96/2800(3.4%)的鱼类中检测到肠膜。鱼类之间的患病率有所不同。阿尔本努斯·查鲁西尼(A.charusini),下眼畸形(H.molitrix),下眼病(H.nobilis),和尖囊裂果(S.Altidorsalis)未显示感染。Schizothoraxzarudnyi(S.zarudnyi)的患病率为1.5%(6/400),鲤鱼(C.carpio)15%(60/400),和鼻咽喉虫(C.idella)7.5%(30/400)。发现感染患病率受C中鱼体重的显着影响。Carpio和C.艾黛拉.在体重较低的鱼类中发现了较高的患病率。不同物种的感染率随季节显著波动,但捕鱼地点没有显著差异。本研究强调了伊朗锡斯坦地区鱼类种群中肠道乳杆菌感染的显著患病率,强调需要不断监测和研究,以告知有效的渔业管理战略。未来的研究应侧重于长期监测工作,并考虑鱼类寄生虫学的更广泛的全球背景,以更好地了解寄生虫与宿主的相互作用,并为全球的保护措施提供信息。
    Fisheries play a crucial role in aquatic ecosystems, a resource with ecological and economic importance. Measuring parasite prevalence is necessary to assess these fish species\' health and well-being. Within the Sistan region, this study sought to estimate the prevalence and intensity of infection with plerocercoid Ligula intestinalis (L. intestinalis) in seven fish species and identify factors such as fish weight, seasonality, and fishing location that might influence infection rates. 2800 fish from seven species were obtained in the Sistan region throughout four seasons. Fish samples from three weight categories (<200gr, 200-400gr, 400gr<) were examined parasitologically. Ligula intestinalis was detected in 96/2800 (3.4%) of fishs. There was a variation in prevalence among fish species. Alburnus charusini (A. charusini), Hypophthalmichthys molitrix (H. molitrix), Hypophthalmichthys nobilis (H. nobilis), and Schizocypris altidorsalis (S. altidorsalis) showed no infection. Schizothorax zarudnyi (S. zarudnyi) showed a prevalence of 1.5% (6/400), Cyprinus carpio (C. carpio) 15% (60/400), and Ctenopharyngodon idella (C. idella) 7.5% (30/400). It was found that infection prevalence was significantly influenced by fish weight in C . carpio and C . idella. A higher prevalence was found in fish with lower weight. Infection rates significantly fluctuated with season across species, but fishing locations had no significant difference. The present study highlights the significant prevalence of L. intestinalis infections in fish populations within Iran\'s Sistan region, underscoring the need for ongoing monitoring and research to inform effective fishery management strategies. Future studies should focus on long-term monitoring efforts and consider the broader global context of fish parasitology to understand parasite-host interactions better and inform conservation measures worldwide.
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  • 文章类型: Case Reports
    蜱传疾病已成为全世界人民健康的威胁,在美国,近80%的患者为载体传播疾病。早期诊断和正确治疗在管理中起着重要作用。密切接触者应筛查与蜱传疾病相关的延迟症状。
    这项研究描述了一个罕见的病例,一名72岁的中国男子在肛周区域有5天的疼痛结节史,指示蜱叮咬。蜱传疾病已成为全世界人民健康的威胁。未经治疗的病例可能会导致几种严重的炎症并发症。用细镊子手动去除蜱对于防止蜱传播感染的传播是有效的。应筛查患者(被蜱虫咬伤)和密切接触者是否有与蜱传播疾病相关的延迟症状。
    UNASSIGNED: Tickborne diseases have become the threats to the health of people worldwide, accounting for nearly 80% patients with vectorborne diseases in the United States. Early diagnosis and proper treatment play a significant role in the management. Close contacts should be screened for delayed symptoms associated with tickborne diseases.
    UNASSIGNED: This study describes a rare case of a 72-year-old Chinese man presented with a 5-day history of painful nodules on the perianal region, indicating tick bite. Tickborne diseases become the threats to the health of people worldwide. Untreated cases may result in several serious inflammatory complications. Manual removal of ticks with fine forceps is effective for preventing the transmission of tickborne infections. People (who have been bitten by a tick) and close contacts should be screened for delayed symptoms associated with tickborne diseases.
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  • 文章类型: Journal Article
    African cichlids are model systems for evolutionary studies and host-parasite interactions, because of their adaptive radiations and because they harbour many species of monogenean parasites with high host-specificity. Five locations were sampled in southern Lake Victoria: gill-infecting monogeneans were surveyed from 18 cichlid species belonging to this radiation superflock and two others representing two older and distantly related lineages. We found one species of Gyrodactylidae, Gyrodactylus sturmbaueri Vanhove, Snoeks, Volckaert & Huyse, 2011, and seven species of Dactylogyridae. Four are described herein: Cichlidogyrus pseudodossoui n. sp., Cichlidogyrus nyanza n. sp., Cichlidogyrus furu n. sp., and Cichlidogyrus vetusmolendarius n. sp. Another Cichlidogyrus species is reported but not formally described (low number of specimens, morphological similarity with C. furu n. sp.). Two other species are redescribed: C. bifurcatus Paperna, 1960 and C. longipenis Paperna & Thurston, 1969. Our results confirm that the monogenean fauna of Victorian littoral cichlids displays lower species richness and lower host-specificity than that of Lake Tanganyika littoral cichlids. In C. furu n. sp., hooks V are clearly longer than the others, highlighting the need to re-evaluate the current classification system that considers hook pairs III-VII as rather uniform. Some morphological features of C. bifurcatus, C. longipenis, and C. nyanza n. sp. suggest that these are closely related to congeners that infect other haplochromines. Morphological traits indicate that representatives of Cichlidogyrus colonised Lake Victoria haplochromines or their ancestors at least twice, which is in line with the Lake Victoria superflock being colonised by two cichlid tribes (Haplochromini and Oreochromini).
    UNASSIGNED: Quatre espèces nouvelles de Cichlidogyrus (Plathelminthes, Monopisthocotyla, Dactylogyridae) parasites d’haplochrominés (Cichlidae) du lac Victoria, avec la redescription de C. bifurcatus et C. longipenis.
    UNASSIGNED: Les cichlidés africains sont des systèmes modèles pour les études évolutives et les interactions hôtes-parasites, en raison de leurs radiations adaptatives et parce qu’ils hébergent de nombreuses espèces de monogènes parasites avec une spécificité d’hôte étroite. Cinq sites ont été échantillonnés dans le sud du lac Victoria, les monogènes infectant les branchies ont été étudiés chez 18 espèces de cichlidés appartenant à ce superflock et de deux autres espèces représentant deux lignées plus anciennes et éloignées. Nous avons trouvé une espèce de Gyrodactylidae, Gyrodactylus sturmbaueri Vanhove, Snoeks, Volckaert & Huyse, 2011, et sept espèces de Dactylogyridae. Quatre sont décrites ici : Cichlidogyrus pseudodossoui n. sp., Cichlidogyrus nyanza n. sp., Cichlidogyrus furu n. sp. et Cichlidogyrus vetusmolendarius n. sp. Une autre espèce de Cichlidogyrus est signalée mais non formellement décrite (faible nombre de spécimens, similarité morphologique avec C. furu n. sp.). Deux autres espèces sont redécrites : C. bifurcatus Paperna, 1960 et C. longipenis Paperna & Thurston, 1969. Nos résultats confirment que la faune des monogènes des cichlidés du littoral du lac Victoria présente une richesse en espèces et une spécificité d’hôte inférieures à celles des cichlidés du littoral du lac Tanganyika. Chez C. furu n. sp., les crochets V sont clairement plus longs que les autres, ce qui souligne la nécessité de réévaluer le système de classification actuel qui considère que les crochets III-VII sont plutôt uniformes. Certaines caractéristiques morphologiques de C. bifurcatus, C. longipenis et C. nyanza n. sp. suggèrent que ceux-ci sont étroitement liés aux congénères qui infectent les autres haplochrominés. Les traits morphologiques indiquent que les représentants de Cichlidogyrus ont colonisé les haplochrominés du lac Victoria ou leurs ancêtres au moins deux fois, ce qui concorde avec le fait que le superflock du lac Victoria a été colonisé par deux tribus de cichlidés (Haplochromini et Oreochromini).
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  • 文章类型: Journal Article
    弓形虫是引起弓形虫病的一种广泛分布的尖丛寄生虫,免疫功能低下个体和先天性感染胎儿的关键健康问题。目前的治疗选择数量有限,并伴有严重的副作用。因此,需要鉴定和开发新的抗弓形虫药物。1-脱氧-D-木酮糖5-磷酸还原异构酶(DXR)被认为是非甲羟戊酸途径中的限速酶,用于生物合成类异戊二烯前体异戊烯焦磷酸(IPP)和二甲基烯丙基二磷酸(DMAPP)在寄生虫中,之前已经研究了它作为一些物种的新型药物靶标的关键作用,包括疟原虫,分枝杆菌和大肠杆菌。在这项研究中,我们展示了弓形虫DXR(TgDXR)在三级复合物中的第一个晶体结构,该复合物与抑制剂膦霉素和辅因子NADPH呈二聚体构象,分辨率为2.5µ,揭示了抑制剂的结合模式。此外,我们在生物学上表征α-苯基-β-thia和-oxa逆转膦霉素类似物,并显示一些衍生物是TgDXR的强抑制剂,与膦霉素相比,体外抑制弓形虫的生长。这里,((3,4-二氯苯基)((2-(羟基(甲基)氨基)-2-氧代乙基)硫代)甲基)膦酸被鉴定为最有效的抗弓形虫化合物。这些发现将使未来设计和开发更有效的抗弓形虫DXR抑制剂成为可能。
    Toxoplasma gondii is a widely distributed apicomplexan parasite causing toxoplasmosis, a critical health issue for immunocompromised individuals and for congenitally infected foetuses. Current treatment options are limited in number and associated with severe side effects. Thus, novel anti-toxoplasma agents need to be identified and developed. 1-Deoxy-d-xylulose 5-phosphate reductoisomerase (DXR) is considered the rate-limiting enzyme in the non-mevalonate pathway for the biosynthesis of the isoprenoid precursors isopentenyl pyrophosphate and dimethylallyl pyrophosphate in the parasite, and has been previously investigated for its key role as a novel drug target in some species, encompassing Plasmodia, Mycobacteria and Escherichia coli. In this study, we present the first crystal structure of T. gondii DXR (TgDXR) in a tertiary complex with the inhibitor fosmidomycin and the cofactor NADPH in dimeric conformation at 2.5 Å resolution revealing the inhibitor binding mode. In addition, we biologically characterize reverse α-phenyl-β-thia and β-oxa fosmidomycin analogues and show that some derivatives are strong inhibitors of TgDXR which also, in contrast with fosmidomycin, inhibit the growth of T. gondii in vitro. Here, ((3,4-dichlorophenyl)((2-(hydroxy(methyl)amino)-2-oxoethyl)thio)methyl)phosphonic acid was identified as the most potent anti T. gondii compound. These findings will enable the future design and development of more potent anti-toxoplasma DXR inhibitors.
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