AbstractParasitic diseases, particularly malaria (caused by Plasmodium falciparum) and theileriosis (caused by Theileria spp.), profoundly impact global health and the socioeconomic well-being of lower-income countries. Despite recent advances, identifying host metabolic proteins essential for these auxotrophic pathogens remains challenging.

摘要寄生虫病，特别是疟疾（由恶性疟原虫引起）和泰勒虫病（由泰勒虫属引起），深刻影响全球健康和低收入国家的社会经济福祉。尽管最近取得了进展，但鉴定这些营养缺陷型病原体所必需的宿主代谢蛋白仍然具有挑战性。

Here, we generate a novel metabolic model of human hepatocytes infected with P. falciparum and integrate it with a genome-wide CRISPR knockout screen targeting Theileria-infected cells to pinpoint shared vulnerabilities. We identify key host metabolic enzymes critical for the intracellular survival of both of these lethal hemoparasites.

在这里，我们产生了一种感染恶性疟原虫的人类肝细胞的新型代谢模型，并将其与靶向泰勒虫感染细胞的全基因组CRISPR敲除筛选相结合，以查明共享的漏洞。我们确定了对这两种致命血液寄生虫的细胞内存活至关重要的关键宿主代谢酶。

Remarkably, among the metabolic proteins identified by our synergistic approach, we find that host purine and heme biosynthetic enzymes are essential for the intracellular survival of P. falciparum and Theileria, while other host enzymes are only essential under certain metabolic conditions, highlighting P.

值得注意的是，在我们的协同方法鉴定的代谢蛋白中，我们发现宿主嘌呤和血红素生物合成酶对于恶性疟原虫和泰勒虫的细胞内存活至关重要，而其他宿主酶仅在某些代谢条件下才是必需的，突出了P。

falciparum’s adaptability and ability to scavenge nutrients selectively. Unexpectedly, host porphyrins emerge as being essential for both parasites. The shared vulnerabilities open new avenues for developing more effective therapies against these debilitating diseases, with the potential for broader applicability in combating apicomplexan infections..

恶性疟原虫的适应性和选择性清除营养物质的能力。出乎意料的是，宿主卟啉对这两种寄生虫都是必不可少的。这些共同的漏洞为开发针对这些衰弱性疾病的更有效疗法开辟了新途径，并有可能在对抗apicomplexan感染方面具有更广泛的适用性。。

IntroductionApicomplexa are unicellular parasites that can cause severe and life-threatening diseases in humans and other animals. The malaria-causing Plasmodium falciparum (P. falciparum) is the most impactful human parasite, with more than 245 million malaria cases and more than 600,000 deaths reported annually1.

简介Apicomplexa是单细胞寄生虫，可在人类和其他动物中引起严重且威胁生命的疾病。引起疟疾的恶性疟原虫（恶性疟原虫）是影响最大的人类寄生虫，每年报告的疟疾病例超过2.45亿，死亡人数超过60万1。

Other socio-economically significant apicomplexans include the related bovine parasites in the genus Theileria, which are responsible for the deaths of more than 1 million cattle annually, significantly impacting livestock productivity, especially in small-scale cattle farming in the Global South2,3.

其他具有社会经济意义的apicomplexans包括泰勒虫属的相关牛寄生虫，每年导致100多万头牛死亡，严重影响牲畜生产力，特别是在全球南方的小型养牛业中2,3。

Notably, highly virulent Theileria species have the unique ability among eukaryotic pathogens to induce cancer-like transformation of host cells, characterized by sustained proliferation and invasiveness4,5,6.A hallmark of apicomplexan parasites is their auxotrophy for multiple metabolites, meaning they lack the ability to synthesize essential nutrients and rely on their host cells.

值得注意的是，高毒力泰勒虫在真核病原体中具有诱导宿主细胞癌症样转化的独特能力，其特征在于持续增殖和侵袭4,5,6。apicomplexan寄生虫的一个标志是它们对多种代谢物的营养缺陷型，这意味着它们缺乏合成必需营养素并依赖宿主细胞的能力。

In recent years, our understanding of apicomplexan metabolism has significantly advanced, revealing significant variation in dependencies among different parasite genera7,8. However, due to the complex interactions with the host cell and the manipulation of key biological processes9,10,11, there remains a lack of comprehensive understanding and detailed insight into the essential metabolic dependencies.

近年来，我们对apicomplexan代谢的理解显着提高，揭示了不同寄生虫基因之间依赖性的显着差异7,8。然而，由于与宿主细胞的复杂相互作用以及关键生物过程的操纵9,10,11，仍然缺乏对基本代谢依赖性的全面理解和详细了解。

We hypothesized that these auxotrophs, depending on their life cycle stage, rely on common host cell-derived metabolites for intracellular survival. Therefore, we explored the potential of targeting a single host metabolic pathway to block infection. Focusing on arguably the two most impactful genera globally, Plasmodium and Theileria, we investigated shared dependencies on key host me.

我们假设这些营养缺陷型依赖于它们的生命周期阶段，依赖于常见的宿主细胞衍生的代谢物进行细胞内存活。因此，我们探索了靶向单一宿主代谢途径以阻断感染的潜力。。

Plasmodium and Theileria schizont survival depend on a core set of shared host enzymesP. falciparum liver-stage infection remains one of the least characterized but most attractive targets for malaria prevention as it represents a bottleneck in parasite development. Experimental limitations, such as the low infection rate and strict biosafety requirements, necessitate the use of metabolic modeling to study the host interplay of the hepatic schizont stages of the human malaria parasite.

疟原虫和泰勒虫裂殖体的存活取决于一组核心的共享宿主酶。恶性疟原虫肝期感染仍然是疟疾预防中特征最少但最具吸引力的目标之一，因为它是寄生虫发展的瓶颈。实验限制，例如低感染率和严格的生物安全要求，需要使用代谢模型来研究人类疟疾寄生虫肝裂殖体阶段的宿主相互作用。

Conversely, T. annulata is well suited for in vitro culturing, as demonstrated by successful CRISPR screening in Theileria-infected macrophages. We investigated whether these pathogens rely on the same host metabolic pathways. We identified 99 metabolic enzymes in our Theileria essentialome and we searched for overlaps with the predicted host gene essentiality for liver stage P.

相反，T.annulata非常适合体外培养，如在泰勒虫感染的巨噬细胞中成功进行CRISPR筛选所证明的。。我们在Theileria essentialome中鉴定了99种代谢酶，并搜索了与预测的肝P期宿主基因必要性的重叠。

falciparum in the auxotrophic and partial prototrophic scenarios. To this end, we identified common host genes that are essential for at least one of the alternative metabolic configurations simulated for liver stage P. falciparum, as well as the list of common host genes essential for all simulated metabolic configurations of P.

营养缺陷型和部分原养型情况下的恶性疟原虫。为此，我们确定了对肝期恶性疟原虫模拟的至少一种替代代谢构型至关重要的常见宿主基因，以及对所有模拟的恶性疟原虫代谢构型至关重要的常见宿主基因列表。

falciparum (Fig. 6). We identified 28 host genes that are commonly essential for Theileria and Plasmodium in at least one of the simulated metabolic configurations, including genes encoding mitochondrial complex II subunits (SDHA, SDHB, SDHC, SDHD) and genes involved in polyamine (AMD1, SRM) and glutathione (GCLC, GSS) biosynthesis (Fig. 6).

恶性疟原虫（图6）。。

Of these only seven genes, belonging to the heme and purine biosynthetic pathways, were identified as commonly essential for Theileria and all simulated metabolic configurations of P. falciparum. This suggests that when metabolites such as polyamines .

在这七个基因中，属于血红素和嘌呤生物合成途径的基因被确定为泰勒虫和恶性疟原虫的所有模拟代谢构型的常见必需基因。这表明当代谢物如多胺时。

The liver-iPfa model was reconstructed from the published iPfa genome-scale model for P. falciparum26 by blocking the reactions that transport in and out of the parasite compounds that are not present in the liver model. By mapping the extra-parasitic metabolites from iPfa to the cytosolic metabolites from the hepatocyte model, we found that from the 241 metabolites that the parasite can transport in the iPfa model, 165 (Supplementary data 1) are present in the cytosol of the liver model.

通过阻断肝脏模型中不存在的寄生虫化合物进出的反应，从已发表的恶性疟原虫iPfa基因组规模模型26重建肝脏iPfa模型。通过将来自iPfa的额外寄生虫代谢物映射到来自肝细胞模型的胞质代谢物，我们发现从寄生虫可以在iPfa模型中运输的241种代谢物中，肝脏模型的胞质溶胶中存在165种（补充数据1）。

We then blocked the transport reactions for the 76 metabolites that are not found in the hepatocyte model and performed flux variability analysis to remove the reactions that could not carry flux in iPfa, resulting in a liver-iPfa model of 737 metabolites, 889 reactions, 210 genes, and a growth of 0.073 h−1 (doubling time of 9.48 h).Minimal nutritional requirements for liver-stage Plasmodium falciparum.

然后，我们阻断了肝细胞模型中未发现的76种代谢物的转运反应，并进行了通量变异性分析，以消除iPfa中不能携带通量的反应，从而产生了737种代谢物，889种反应，210个基因的肝脏iPfa模型，生长为0.073h-1（倍增时间为9.48h）。肝期恶性疟原虫的最低营养需求。

In order to investigate the minimal set of nutrients that the liver-stage P. falciparum needs to sustain growth, we applied the in silico minimal medium (iMM) method30 to the liver-iPfa model. The iMM method identifies the minimal set of nutrients that are required to satisfy a specific growth rate.

为了研究肝脏恶性疟原虫维持生长所需的最小营养成分，我们将计算机模拟基本培养基（iMM）方法30应用于肝脏iPfa模型。iMM方法确定了满足特定生长速度所需的最小营养素组。

In this case, we identified that parasites need a minimum of 31 nutrients to grow. Given the flexibility of the intracellular metabolism to synthesize the required precursors for biomass, there exist alternative sets of nutrients that could serve to achieve the same growth rate. In this case, using iMM we found 1792 alternative sets of 31 nutrients, leading to a total of 47 unique nutrients across sets.

在这种情况下，我们发现寄生虫至少需要31种营养才能生长。鉴于细胞内代谢的灵活性，可以合成生物质所需的前体，因此存在替代营养素组，可以实现相同的生长速度。在这种情况下，使用iMM，我们发现了1792组31种营养素的替代组，导致每组共有47种独特的营养素。

By classifying the presence of these nutrients in the corresponding 1792 sets, we identified 23 nutrients that appear in all sets, which we call constitutive, and 24 nutrients that are not appearing systematically in all sets because they can substitute each other, as they contribute with the same backbone moieties (Fig. S1a and Supplementary data 1).In this scenario, when considering a liver-stage P.

通过对相应1792组中这些营养素的存在进行分类，我们确定了所有组中出现的23种营养素，我们称之为组成型营养素，以及24种营养素，这些营养素在所有组中都没有系统地出现，因为它们可以相互替代，因为它们具有相同的骨架部分（图S1a和补充数据1）。在这种情况下，当考虑肝脏阶段P时。

falciparum that takes up the minimal number of metabolites from its host cell, we are simulating a partial prototrophic parasite. Such a parasite can synthesize the maximum number of biomass precursors and will only scavenge from the host those that it cannot synthesize itself.The parasitosome as a representation of the metabolic state of Plasmodium falciparum.

。这样的寄生虫可以合成最大数量的生物质前体，并且只能从宿主身上清除那些它无法自行合成的前体。寄生虫体作为恶性疟原虫代谢状态的代表。

The parasitosome is a unidirectional metabolic reaction defined by the following steps:

寄生虫体是由以下步骤定义的单向代谢反应：

1.

1.

Set the extracellular composition in the parasite model. We considered two cases: (i) parasites in an auxotrophic mode, which take up the available nutrients from the host cytosol, (ii) parasites in a partial prototrophic mode, which take up the minimum amount of nutrients from the host and use their intracellular metabolism to synthesize the rest of the compounds required for growth..

在寄生虫模型中设置细胞外成分。我们考虑了两种情况：（i）营养缺陷型寄生虫，它从宿主细胞质中吸收可用的营养，（ii）部分原养型寄生虫，它从宿主中吸收最少量的营养，并利用它们的细胞内代谢来合成生长所需的其余化合物。。

2.

2.

Use the lumpGEM method51 in the liver-iPfa model to identify the set of intracellular reactions that must be active to simulate parasite growth. This subnetwork is known as minimal network (MiN).

在肝脏iPfa模型中使用lumpGEM方法51来鉴定必须活跃以模拟寄生虫生长的一组细胞内反应。该子网称为最小网络（MiN）。

3.

3.

Then, lumpGEM generates a lumped reaction by collapsing the subnetwork into one reaction (see original publication for more details). In the resulting reaction, substrates represent the nutrients that the parasite takes up from the host’s cytosol, and products represent the by-products that the parasite must secrete into the host’s cytosol..

然后，lumpGEM通过将子网折叠成一个反应来生成一个集总反应（有关更多详细信息，请参见原始出版物）。在由此产生的反应中，底物代表寄生虫从宿主细胞质中吸收的营养物质，产物代表寄生虫必须分泌到宿主细胞质中的副产物。。

It is important to note that the subnetwork generated by lumpGEM contains the details of the metabolic reactions active for the corresponding metabolic configuration as well as the biomass reaction of the parasite. As a result, one of the metabolites in the parasitosome reaction is the parasite biomass.

重要的是要注意，由lumpGEM生成的子网络包含对相应代谢构型以及寄生虫的生物量反应活跃的代谢反应的细节。因此，寄生虫体反应中的代谢物之一是寄生虫生物量。

Therefore, the optimized flux through the parasitosome in the integrated model represents the overall growth of the parasite by uptake and secretion of compounds from and to the host cytosol. Note that the parasitosome can support growth up to the maximum value but it can also capture suboptimal growth.The directionality of each parasitosome, as well as the directionality of the reactions composing the underlying subnetwork are determined by lumpGEM.

因此，在综合模型中通过寄生虫体的优化通量代表了寄生虫通过从宿主细胞质和向宿主细胞质摄取和分泌化合物的总体生长。请注意，寄生体可以支持生长达到最大值，但也可以捕获次优生长。每个寄生体的方向性以及组成底层子网的反应的方向性由lumpGEM确定。

The algorithm finds the optimal configuration of fluxes that maximize biomass production in the parasite model, taking into account the directionality and thermodynamic feasibility of the reactions as defined in the curated GEM.Note also that the alternative biochemistry of the parasite leads to alternative metabolic configurations (subnetworks) and thus to alternative parasitosomes.In the case that we simulate an auxotrophic parasite, a minimum of 248 reactions are required and there exist 151 alternative MiNs (Fig. S1c).

该算法考虑到策划的GEM中定义的反应的方向性和热力学可行性，找到了在寄生虫模型中最大化生物量产生的通量的最佳配置。还请注意，寄生虫的替代生物化学导致替代代谢构型（子网），从而导致替代寄生虫体。在我们模拟营养缺陷型寄生虫的情况下，至少需要248个反应，并且存在151个替代分钟（图S1c）。

By lumping the MiNs into individual reactions, we generated 151 parasitosomes that use a total of 75 nutrients and secrete a total of 27 products (Fig. S1b). In the case where the parasite is in a partial prototrophic mode, the size of the MiNs is 307 reactions and there exist 8 alternatives (Fig. S1c), resulting in 8 alternative parasitosomes that take up a total of 36 nutrients and secrete 36 products (Fig. S1b).Reconstruction of a hepatocyte-parasite integrated metabolic modelThe generated parasitosome .

。在寄生虫处于部分原养模式的情况下，MiNs的大小为307个反应，存在8个替代物（图S1c），产生8个替代寄生虫体，共吸收36种营养素并分泌36种产物（图S1b）。肝细胞-寄生虫整合代谢模型的重建产生的寄生虫体。

Plasmodium berghei infectionHAP1 cells were cultured in IMDM (Bioconcept, containing 10% FCS, 4 mM L-glutamine, 100 U penicillin, 100 µg/ml streptomycin) at 37 °C, 5% CO2. To infect confluent cultures, 70,000 cells were seeded in 96 well plates. The next day, the cultures were infected with 20,000 freshly isolated sporozoites.

伯氏疟原虫感染HAP1细胞在IMDM（Bioconcept，含有10%FCS，4 mM L-谷氨酰胺，100 U青霉素，100µg/ml链霉素）中于37℃，5%CO2下培养。为了感染融合培养物，将70000个细胞接种在96孔板中。第二天，培养物被20000个新鲜分离的子孢子感染。

To allow development over 48 h, cultures were expanded by passaging with accutase (Innovative Cell Technologies) at 2 hpi. Cells were reseeded into 96 well plates (Greiner µClear, 655090). Each infected well was divided into 12 wells. At 48 hpi, cells were imaged with a Nikon Ti2 inverted fluorescence microscope Plan Apo λD 10× (NA 0.45) objective, Spectra X light engine (555 nm line, Lumencor), acquired with a Kinetix22 camera (Photometrix), Pinkel quad and Sedat quad filter sets (MXR00244 and MXR00254, Semrock).

为了使发育超过48小时，通过在2 hpi下用accutase（Innovative Cell Technologies）传代来扩增培养物。将细胞重新接种到96孔板中（GreinerµClear，655090）。将每个感染的孔分成12个孔。在48 hpi时，用尼康Ti2倒置荧光显微镜Plan ApoλD 10x（NA 0.45）物镜，Spectra X光引擎（555nm线，Lumencor）对细胞成像，用Kinetix22相机（Photometrix），Pinkel quad和Semat quad滤光片组（MXR00244和MXR00254，Semrock）采集。

Parasite sizes were segmented and analyzed using the General Analysis Module of NIS-Elements 5.42.02. Graphs were generated with Prism 9 (GraphPad) and indicate medians with interquartile range. One-way ANOVA with Dunnett’s multiple comparison was used as statistical evaluation, adjusted p values are presented directly in the graph.Software for data analyses and computationThe metabolic modeling computational analyses were performed using Matlab (MathWorks, v2021b) and CPLEX (IBM, v12.10).

使用NIS Elements 5.42.02的通用分析模块对寄生虫大小进行分割和分析。使用Prism 9（GraphPad）生成图形，并指示具有四分位间距的中位数。使用Dunnett多重比较的单因素方差分析作为统计评估，调整后的p值直接显示在图中。数据分析和计算软件使用Matlab（MathWorks，v2021b）和CPLEX（IBM，v12.10）进行代谢建模计算分析。

Data analyses and associated graphs were generated with Rstudio, Microsoft Excel, FlowJo, and Prism 9 (GraphPad).Reporting summaryFurther information on research design is available in the Nature Portfolio Reporting Summary linked to this article..

。报告摘要有关研究设计的更多信息，请参阅本文链接的Nature Portfolio Reporting Summary。。

Data availability

数据可用性

CRISPR screen data for this study have been deposited in the European Nucleotide Archive (ENA) at EMBL-EBI under accession number PRJEB73635 and accession numbers for the RNA-seq data for uninfected macrophages (ERS16273013, ERS16273014, ERS16273015) and TaC12 cells (ERS18408949, ERS18408950, ERS18408951) (https://www.ebi.ac.uk/ena/).

这项研究的CRISPR筛选数据已保存在EMBL-EBI的欧洲核苷酸档案（ENA）中，登录号为PRJEB73635，未感染巨噬细胞（ERS16273013，ERS16273014，ERS16273015）和TaC12细胞（ERS18408949，ERS18408950，ERS18408951）的RNA-seq数据的登录号(https://www.ebi.ac.uk/ena/)。

Chip files for the genome wide bovine library (CP1273, 85155 distinct barcodes) and the sublibrary (CP1504, 17596 distinct barcodes) have been uploaded as supplementary files. Source data are provided with this paper..

全基因组牛文库（CP127385155个不同条形码）和子文库（CP150417596个不同条形码）的芯片文件已作为补充文件上传。本文提供了源数据。。

Code availability

代码可用性

The code to generate the results for this paper is available under the APACHE 2.0 license at https://github.com/EPFL-LCSB/host_parasite_interactions. The code for TFA is available at https://github.com/EPFL-LCSB/mattfa. The code to identify minimal nutrients (iMM) is available at https://github.com/EPFL-LCSB/redhuman..

生成本文结果的代码可在APACHE 2.0许可证下获得，网址为https://github.com/EPFL-LCSB/host_parasite_interactions.https://github.com/EPFL-LCSB/mattfa.识别最低营养素（iMM）的代码可在https://github.com/EPFL-LCSB/redhuman..

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Galmozzi, A. et al. PGRMC2 is an intracellular haem chaperone critical for adipocyte function. Nature 576, 138–142 (2019).Article

Galmozzi，A。等人，PGRMC2是一种对脂肪细胞功能至关重要的细胞内血红素伴侣。自然576138-142（2019）。文章

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Download referencesAcknowledgementsWe would like to express our gratitude to Francis Brühlmann for providing the IFA image of Theileria annulata used in Fig. 1. We thank the Flow Cytometry and Cell Sorting Facility (FCCS) of the Department for BioMedical Research (DBMR) of the University of Bern, Switzerland.

下载参考文献致谢我们要感谢Francis Brühlmann提供图1中使用的Theileria annulata的IFA图像。我们感谢瑞士伯尔尼大学生物医学研究系（DBMR）的流式细胞仪和细胞分选设备（FCCS）。

Financial support came from the University of Bern (UniBe ID grant to S.R. and V.He.) and the Swiss National Science Foundation (198543 to S.R., V.He., V.Ha., 189127 to S.R., 173972 to P.O.). Figures were created with the help of BioRender.FundingOpen Access funding enabled and organized by Projekt DEAL.Author informationAuthor notesThese authors contributed equally: Marina Maurizio, Maria Masid.Authors and AffiliationsInstitute of Animal Pathology, Vetsuisse Faculty, University of Bern, Bern, SwitzerlandMarina Maurizio, Kerry Woods, Arunasalam Naguleswaran, Martín González-Fernández, Jonas Zemp, Sven Rottenberg & Philipp OliasLudwig Institute for Cancer Research, Department of Oncology, University of Lausanne and Lausanne University Teaching Hospital (CHUV), Lausanne, SwitzerlandMaria MasidLaboratory of Computational Systems Biotechnology, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, SwitzerlandMaria Masid, Denis Joly, Mélanie Borteele & Vassily HatzimanikatisInstitute of Cell Biology, University of Bern, Bern, SwitzerlandReto Caldelari, Jonas Zemp & Volker HeusslerBroad Institute of MIT and Harvard, Cambridge, MA, USAJohn G.

财政支持来自伯尔尼大学（UniBe ID授予S.R.和V.He。）和瑞士国家科学基金会（198543授予S.R.，V.He.，V.Ha.，189127授予S.R.，173972授予P.O.）。数字是在BioRender的帮助下创建的。资金开放获取资金由Projekt交易启用和组织。作者信息作者注意到这些作者做出了同样的贡献：Marina Maurizio，Maria Masid。作者和附属机构伯尔尼大学兽医学院动物病理学研究所，伯尔尼，瑞士马里纳·莫里齐奥，克里·伍兹，阿鲁纳萨兰·纳古列斯瓦兰，马丁冈萨雷斯·费尔南德斯，乔纳斯·泽姆，斯文·罗滕贝格和菲利普·奥利亚斯路德维希癌症研究所，洛桑大学肿瘤系和洛桑大学教学医院（CHUV），洛桑，瑞士马西德计算系统生物技术实验室，洛桑理工学院（EPFL），洛桑Tzerlandmaria Masid，Denis Joly，Mélanie Borteele＆Vassily HatzimanikatisInstitute of Cell Biology，伯尔尼大学，瑞士人Caldelari，Jonas Zemp＆Volker HeusslerBroad Institute of MIT和哈佛大学，剑桥，马萨诸塞州，美国约翰·G。

DoenchInstitute of Veterinary Pathology, Justus Liebig University, Giessen, GermanyPhilipp OliasAuthorsMarina MaurizioView author publicationsYou can also search for this author in.

DoenchInstitute of Veterinary Pathology，Justus Liebig University，Giessen，GermanyPhilipp OliasAuthorsMarina MaurizioView作者出版物您也可以在中搜索这位作者。

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PubMed Google ScholarContributionsConceptualization, K.W., S.R., P.O.; methodology, J.G.D., K.W., V.Hr., V.Ha., S.R., P.O.; investigation, M.Mr., M.Ms., K.W., R.C., A.N., D.J., J.Z., M.B.; formal analysis, M.Mr., M.Ms., K.W., R.C., A.N., M.G.F., P.O.; writing – original draft, M.Mr., M.Ms.; writing – review & editing, K.W., R.C., J.G.D., A.N., V.Hr., V.Ha., S.R., P.O.; funding acquisition, V.Ha., V.Hr., S.R., P.O.; resources, V.Ha., V.Hr., S.R., P.O.; supervision, V.Ha., V.Hr., S.R., P.O.Corresponding authorsCorrespondence to.

PubMed谷歌学术贡献概念化，K.W.，S.R.，P.O。；方法论，J.G.D.，K.W.，V.Hr.，V.Ha。，S、 R.，P.O。；调查，M.Mr.，M.Ms.，K.W.，R.C.，A.N.，D.J.，J.Z.，M.B。；正式分析，M.Mr.，M.Ms.，K.W.，R.C.，A.N.，M.G.F.，P.O。；写作-原稿，M.Mr.，M.Ms。；写作-评论与编辑，K.W.，R.C.，J.G.D.，A.N.，V.Hr.，V.Ha。，S、 R.，P.O。；资金收购，V.Ha。，五、 人力资源，S.R.，P.O。；资源，V.Ha。，五、 人力资源，S.R.，P.O。；监督，V.Ha。，五、 Hr。，S.R。，P.O。通讯作者通讯。

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Nature Communications thanks Jennifer Guler and the other anonymous reviewer(s) for their contribution to the peer review of this work. A peer review file is available.

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Reprints and permissionsAbout this articleCite this articleMaurizio, M., Masid, M., Woods, K. et al. Host cell CRISPR genomics and modelling reveal shared metabolic vulnerabilities in the intracellular development of Plasmodium falciparum and related hemoparasites.

转载和许可本文引用本文Maurizio，M.，Masid，M.，Woods，K。等人。宿主细胞CRISPR基因组学和建模揭示了恶性疟原虫和相关血液寄生虫的细胞内发育中共有的代谢脆弱性。

Nat Commun 15, 6145 (2024). https://doi.org/10.1038/s41467-024-50405-xDownload citationReceived: 01 November 2023Accepted: 01 July 2024Published: 21 July 2024DOI: https://doi.org/10.1038/s41467-024-50405-xShare this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

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