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Protection against Clostridioides difficile disease by a naturally avirulent strain 用天然无毒菌株预防艰难梭菌病
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-11-27 DOI: 10.1016/j.chom.2024.11.003
Qiwen Dong, Stephen Harper, Emma McSpadden, Sophie S. Son, Marie-Maude Allen, Huaiying Lin, Rita C. Smith, Carolyn Metcalfe, Victoria Burgo, Che Woodson, Anitha Sundararajan, Amber Rose, Mary McMillin, David Moran, Jessica Little, Michael W. Mullowney, Ashley M. Sidebottom, Louis-Charles Fortier, Aimee Shen, Eric G. Pamer
Clostridioides difficile is a leading cause of healthcare infections. Gut dysbiosis promotes C. difficile infection (CDI) and CDIs promote gut dysbiosis, leading to frequent CDI recurrence. Although therapies preventing recurrent CDI have been developed, including live biotherapeutic products, existing therapies are costly and do not prevent primary infections. Here, we show that an avirulent C. difficile isolate, ST1-75, protects mice from developing colitis induced by a virulent R20291 strain when coinfected at a 1:1 ratio. In metabolic analyses, avirulent ST1-75 depletes amino acids more rapidly than virulent R20291 and supplementation with amino acids ablates this competitive advantage, indicating that ST1-75 limits the growth of virulent R20291 through amino acid depletion. Overall, our study identifies inter-strain nutrient depletion as a potentially exploitable mechanism to reduce the incidence of CDI and reveals that the ST1-75 strain may be a biotherapeutic agent that can prevent CDI in high-risk patients.
艰难梭菌是造成医疗感染的主要原因。肠道菌群失调会促进艰难梭菌感染(CDI),而艰难梭菌感染又会促进肠道菌群失调,导致艰难梭菌感染频繁复发。虽然已经开发出了包括活生物治疗产品在内的预防复发性 CDI 的疗法,但现有疗法成本高昂,而且不能预防原发性感染。在这里,我们展示了一种无毒艰难梭菌分离物 ST1-75,当以 1:1 的比例共同感染毒性 R20291 菌株时,它能保护小鼠免于患上毒性 R20291 菌株诱发的结肠炎。在代谢分析中,无毒的 ST1-75 比有毒力的 R20291 更快地消耗氨基酸,而补充氨基酸会削弱这种竞争优势,这表明 ST1-75 通过消耗氨基酸限制了有毒力的 R20291 的生长。总之,我们的研究将菌株间的营养消耗确定为降低 CDI 发病率的潜在可利用机制,并揭示了 ST1-75 菌株可能是一种生物治疗剂,可预防高危患者的 CDI。
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引用次数: 0
Zinc promotes microbial p-coumaric acid production that protects against cholestatic liver injury 锌能促进微生物产生对香豆酸,从而防止胆汁淤积性肝损伤
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-11-27 DOI: 10.1016/j.chom.2024.11.002
Dongping Li, Meijuan Wan, Lanfeng Xue, Zhelin Zhang, Yifeng Qiu, Fengyi Mei, Niexing Tang, Chunxiao Yu, Yao Yu, Tianqi Chen, Xing Ding, Qin Yang, Qiuyan Liu, Peng Gu, Wei Jia, Yu Chen, Peng Chen
Cholestatic liver disease (CLD) is a common liver disorder with limited treatment options. Here, we demonstrate that zinc (Zn) supplementation can alter the gut microbiome to mitigate cholestatic liver injury. Oral Zn altered the microbiota of mice and humans (this study was registered at clinicaltrials.gov [NCT05597137]), increasing the abundance of Blautia producta (B. producta) and promoting the generation of p-coumaric acid. Additionally, p-coumaric acid concentrations were negatively correlated with liver injury parameters in CLD patients. In mice, the protective effects of Zn were partially mediated by p-coumaric acid, which directly bound to nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) and suppressed the production of reactive oxygen species (ROS) in hepatocytes, thus preventing hepatocyte cell death and liver damage. Additionally, knocking out the histidine ammonia-lyase, which catalyzes the conversion of tyrosine to p-coumaric acid in B. producta, blunted the protective effects of Zn. These findings highlight a host-microbiota interaction that is stimulated by Zn supplementation, providing potential benefits for CLD.
胆汁淤积性肝病(CLD)是一种常见的肝脏疾病,治疗方法有限。在这里,我们证明了补充锌(Zn)可以改变肠道微生物群,从而减轻胆汁淤积性肝损伤。口服锌可改变小鼠和人类的微生物群(该研究已在 clinicaltrials.gov [NCT05597137] 注册),增加产品鳢(B. producta)的丰度并促进对香豆酸的生成。此外,对香豆酸的浓度与CLD患者的肝损伤参数呈负相关。在小鼠中,锌的保护作用部分由对香豆酸介导,对香豆酸直接与烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶 2(NOX2)结合,抑制肝细胞中活性氧(ROS)的产生,从而防止肝细胞死亡和肝损伤。此外,敲除 B. producta 中催化酪氨酸转化为对香豆酸的组氨酸氨化酶也削弱了锌的保护作用。这些发现突显了宿主与微生物群之间的相互作用,补充锌可刺激宿主与微生物群之间的相互作用,从而为慢性阻塞性肺病提供潜在的益处。
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引用次数: 0
A nucleoside signal generated by a fungal endophyte regulates host cell death and promotes root colonization 真菌内生菌产生的核苷信号可调控宿主细胞死亡并促进根系定殖
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-11-26 DOI: 10.1016/j.chom.2024.10.020
Nick Dunken, Heidi Widmer, Gerd U. Balcke, Henryk Straube, Gregor Langen, Nyasha M. Charura, Pia Saake, Concetta De Quattro, Jonas Schön, Hanna Rövenich, Stephan Wawra, Mamoona Khan, Armin Djamei, Matias D. Zurbriggen, Alain Tissier, Claus-Peter Witte, Alga Zuccaro
The intracellular colonization of plant roots by the beneficial fungal endophyte Serendipita indica follows a biphasic strategy, including a host cell death phase that enables successful colonization of Arabidopsis thaliana roots. How host cell death is initiated and controlled is largely unknown. Here, we show that two fungal enzymes, the ecto-5′-nucleotidase SiE5NT and the nuclease SiNucA, act synergistically in the apoplast at the onset of cell death to produce deoxyadenosine (dAdo). The uptake of extracellular dAdo but not the structurally related adenosine activates cell death via the equilibrative nucleoside transporter ENT3. We identified a previously uncharacterized Toll-like interleukin 1 receptor (TIR)-nucleotide-binding leucine-rich repeat receptor (NLR) protein, ISI (induced by S. indica), as an intracellular factor that affects host cell death, fungal colonization, and growth promotion. Our data show that the combined activity of two fungal apoplastic enzymes promotes the production of a metabolite that engages TIR-NLR-modulated pathways to induce plant cell death, providing a link to immunometabolism in plants.
有益真菌内生菌 Serendipita indica 在植物根部的细胞内定植遵循一种双相策略,其中包括使拟南芥根部成功定植的宿主细胞死亡阶段。宿主细胞死亡是如何启动和控制的,目前尚不清楚。在这里,我们发现两种真菌酶,即外向-5′-核苷酸酶 SiE5NT 和核酸酶 SiNucA,在细胞死亡开始时协同作用于细胞外质,产生脱氧腺苷(dAdo)。细胞外 dAdo 而非结构相关的腺苷的摄取会通过平衡核苷转运体 ENT3 激活细胞死亡。我们发现了一种以前未定性的 Toll 样白细胞介素 1 受体(TIR)-核苷酸结合富亮氨酸重复受体(NLR)蛋白 ISI(由 S. indica 诱导),它是一种影响宿主细胞死亡、真菌定殖和生长促进的细胞内因子。我们的数据表明,两种真菌凋亡酶的联合活性促进了一种代谢物的产生,这种代谢物通过 TIR-NLR 调节的途径诱导植物细胞死亡,从而为植物的免疫代谢提供了一种联系。
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引用次数: 0
Prenatal antibiotics reduce breast milk IgA and induce dysbiosis in mouse offspring, increasing neonatal susceptibility to bacterial sepsis 产前抗生素会降低母乳中的 IgA,诱发小鼠后代菌群失调,增加新生儿对细菌性败血症的易感性
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-11-26 DOI: 10.1016/j.chom.2024.11.001
Carlo Pietrasanta, Carolina Carlosama, Michela Lizier, Giulia Fornasa, Tanja Rezzonico Jost, Sara Carloni, Silvia Giugliano, Alessandra Silvestri, Paola Brescia, Benedetta De Ponte Conti, Daniele Braga, Martin Mihula, Lavinia Morosi, Alessandro Bernardinello, Andrea Ronchi, Giuseppe Martano, Fabio Mosca, Giuseppe Penna, Fabio Grassi, Lorenza Pugni, Maria Rescigno
Antibiotics (Abx) are administered to 20%–30% of pregnant women, but their effects on neonatal immune development are poorly understood. We show that newborn mice born to Abx-treated dams are more susceptible to late-onset sepsis. This susceptibility is linked to lower maternal breast milk immunoglobulin A (IgA), neonatal fecal IgA, and IgA coating of intestinal bacteria, thus causing the translocation of intestinal pathobionts. Weaned young adults born to Abx-treated mothers had reduced IgA+ plasma cells in the ileum and colon, fecal secretory IgA (SIgA), colonic CD4+ T regulatory lymphocytes and T helper 17-like lymphocytes, and a less diverse fecal microbiome. However, treatment with apyrase, which restores SIgA secretion, prompted IgA production in breast milk and protected pups from sepsis. Additionally, breast milk from untreated mothers rescued the phenotypes of pups born to Abx-treated mothers. Our data highlight the impact of prenatal Abx on breast milk IgA and their long-term influence on intestinal mucosal immune function mediated by breastfeeding.
20%-30%的孕妇会服用抗生素(Abx),但人们对抗生素对新生儿免疫系统发育的影响知之甚少。我们的研究表明,服用过抗生素的母鼠所生的新生小鼠更容易患晚期败血症。这种易感性与较低的母体母乳免疫球蛋白 A (IgA)、新生儿粪便 IgA 和肠道细菌的 IgA 涂层有关,从而导致肠道病原菌的转移。经 Abx 处理的母亲所生的断奶后的年轻成人回肠和结肠中的 IgA+ 浆细胞、粪便分泌型 IgA(SIgA)、结肠 CD4+ T 调节性淋巴细胞和 T 辅助细胞 17 样淋巴细胞减少,粪便微生物群的多样性降低。然而,使用能恢复 SIgA 分泌的 apyrase 治疗可促进母乳中 IgA 的分泌,并保护幼崽免受败血症的影响。此外,未接受过治疗的母亲所产的母乳可挽救接受过 Abx 治疗的母亲所生幼崽的表型。我们的数据强调了产前 Abx 对母乳 IgA 的影响,以及它们对母乳喂养所介导的肠粘膜免疫功能的长期影响。
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引用次数: 0
A metagenome-assembled genome inventory for children reveals early-life gut bacteriome and virome dynamics 元基因组组装的儿童基因组清单揭示了生命早期肠道细菌组和病毒组的动态变化
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-11-25 DOI: 10.1016/j.chom.2024.10.017
Ye Peng, Jie Zhu, Shilan Wang, Yingzhi Liu, Xin Liu, Orlando DeLeon, Wenyi Zhu, Zhilu Xu, Xi Zhang, Shilin Zhao, Suisha Liang, Hang Li, Brian Ho, Jessica Yuet-Ling Ching, Chun Pan Cheung, Ting Fan Leung, Wing Hung Tam, Tak Yeung Leung, Eugene B. Chang, Francis Ka Leung Chan, Hein Min Tun
Existing microbiota databases are biased toward adult samples, hampering accurate profiling of the infant gut microbiome. Here, we generated a metagenome-assembled genome inventory for children (MAGIC) from a large collection of bulk and viral-like particle-enriched metagenomes from 0 to 7 years of age, encompassing 3,299 prokaryotic and 139,624 viral species-level genomes, 8.5% and 63.9% of which are unique to MAGIC. MAGIC improves early-life microbiome profiling, with the greatest improvement in read mapping observed in Africans. We then identified 54 candidate keystone species, including several Bifidobacterium spp. and four phages, forming guilds that fluctuated in abundance with time. Their abundances were reduced in preterm infants and were associated with childhood allergies. By analyzing the B. longum pangenome, we found evidence of phage-mediated evolution and quorum sensing-related ecological adaptation. Together, the MAGIC database recovers genomes that enable characterization of the dynamics of early-life microbiomes, identification of candidate keystone species, and strain-level study of target species.
现有的微生物群数据库偏重于成人样本,妨碍了对婴儿肠道微生物群的准确分析。在这里,我们从大量富含病毒样颗粒的0到7岁儿童元基因组中生成了元基因组组装的儿童基因组库(MAGIC),其中包括3299个原核生物基因组和139624个病毒物种级基因组,其中8.5%和63.9%是MAGIC所独有的。MAGIC 改进了生命早期微生物组图谱分析,在非洲人中观察到的读图映射改进最大。然后,我们确定了 54 个候选的关键物种,包括几个双歧杆菌属和四个噬菌体,它们组成了丰度随时间波动的行会。它们在早产儿中的丰度降低,并与儿童过敏症有关。通过分析B. longum庞基因组,我们发现了噬菌体介导的进化和与法定量感应相关的生态适应的证据。总之,MAGIC 数据库所恢复的基因组能够描述生命早期微生物群的动态特征、鉴定候选关键物种以及对目标物种进行菌株级研究。
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引用次数: 0
A trivalent mucosal vaccine encoding phylogenetically inferred ancestral RBD sequences confers pan-Sarbecovirus protection in mice 编码系统发育推断出的祖先 RBD 序列的三价粘膜疫苗可为小鼠提供泛沙巴病毒保护
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-11-18 DOI: 10.1016/j.chom.2024.10.016
James Brett Case, Shilpa Sanapala, Carly Dillen, Victoria Rhodes, Christian Zmasek, Taras M. Chicz, Charlotte E. Switzer, Suzanne M. Scheaffer, George Georgiev, Catherine Jacob-Dolan, Blake M. Hauser, Déborah Carolina Carvalho Dos Anjos, Lucas J. Adams, Nadia Soudani, Chieh-Yu Liang, Baoling Ying, Ryan P. McNamara, Richard H. Scheuermann, Adrianus C.M. Boon, Daved H. Fremont, Michael S. Diamond
The continued emergence of SARS-CoV-2 variants and the threat of future Sarbecovirus zoonoses have spurred the design of vaccines that can induce broad immunity against multiple coronaviruses. Here, we use computational methods to infer ancestral phylogenetic reconstructions of receptor binding domain (RBD) sequences across multiple Sarbecovirus clades and incorporate them into a multivalent adenoviral-vectored vaccine. Mice immunized with this pan-Sarbecovirus vaccine are protected in the upper and lower respiratory tracts against infection by historical and contemporary SARS-CoV-2 variants, SARS-CoV, and pre-emergent SHC014 and Pangolin/GD coronavirus strains. Using genetic and immunological approaches, we demonstrate that vaccine-induced protection unexpectedly is conferred principally by CD4+ and CD8+ T cell-mediated anamnestic responses. Importantly, prior mRNA vaccination or SARS-CoV-2 respiratory infection does not alter the efficacy of the mucosally delivered pan-Sarbecovirus vaccine. These data highlight the promise of a phylogenetic approach for antigen and vaccine design against existing and pre-emergent Sarbecoviruses with pandemic potential.
SARS-CoV-2 变异体的不断出现以及未来 Sarbecovirus 人畜共患病的威胁促使人们设计能诱导多种冠状病毒广泛免疫的疫苗。在本文中,我们使用计算方法推断了多个沙棘病毒支系的受体结合域(RBD)序列的祖先系统发育重建,并将其纳入多价腺病毒载体疫苗中。小鼠接种这种泛沙士病毒疫苗后,上呼吸道和下呼吸道均可免受历史和当代 SARS-CoV-2 变体、SARS-CoV 以及 SHC014 和 Pangolin/GD 冠状病毒毒株的感染。我们利用遗传学和免疫学方法证明,疫苗诱导的保护作用出乎意料地主要由 CD4+ 和 CD8+ T 细胞介导的过敏反应产生。重要的是,之前的 mRNA 疫苗接种或 SARS-CoV-2 呼吸道感染不会改变粘膜递送的泛沙士病毒疫苗的功效。这些数据凸显了系统发育方法在抗原和疫苗设计方面的前景,这种方法可用于抗击现有的和爆发前的具有大流行潜力的沙士病毒。
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引用次数: 0
Harnessing biosynthesized selenium nanoparticles for recruitment of beneficial soil microbes to plant roots 利用生物合成的硒纳米颗粒招募有益的土壤微生物进入植物根系
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-11-18 DOI: 10.1016/j.chom.2024.10.015
Chenyu Sun, Bin Sun, Lin Chen, Meilin Zhang, Pingping Lu, Mengfan Wu, Quanhong Xue, Qiao Guo, Dejian Tang, Hangxian Lai
Root exudates can benefit plant growth and health by reshaping the rhizosphere microbiome. Whether nanoparticles biosynthesized by rhizosphere microbes play a similar role in plant microbiome manipulation remains enigmatic. Herein, we collect elemental selenium nanoparticles (SeNPs) from selenobacteria associated with maize roots. In vitro and soil assays show that the SeNPs enhanced plant performance by recruiting plant growth-promoting bacteria (e.g., Bacillus) in a dose-dependent manner. Multiomic profilings unravel a cross-kingdom-signaling cascade that mediates efficient biosynthesis of SeNPs by selenobacteria. Specifically, maize roots perceive histamine signaling from Bacillus spp., which stimulates the plant to produce p-coumarate via root exudation. The rpoS gene in selenobacteria (e.g., Pseudomonas sp. ZY71) responds to p-coumarate signaling and positively regulates the biosynthesis of SeNPs. This study demonstrates a novel mechanism for recruiting host-beneficial soil microbes by microbially synthesized nanoparticles and unlocks promising possibilities for plant microbiome manipulation.
根渗出物可以通过重塑根圈微生物组来促进植物生长和健康。根圈微生物生物合成的纳米颗粒是否在植物微生物群操纵中发挥类似作用仍是一个谜。在这里,我们从与玉米根系相关的硒细菌中收集元素硒纳米颗粒(SeNPs)。体外和土壤试验表明,SeNPs 能以剂量依赖的方式招募促进植物生长的细菌(如芽孢杆菌),从而提高植物的生长性能。多组学分析揭示了硒细菌高效生物合成 SeNPs 的跨领域信号级联。具体来说,玉米根部能感知来自芽孢杆菌的组胺信号,从而刺激植物通过根部渗出产生对香豆酸盐。硒细菌(如假单胞菌 ZY71)中的 rpoS 基因会响应对香豆酸信号,并积极调节 SeNPs 的生物合成。这项研究展示了微生物合成的纳米颗粒招募对宿主有益的土壤微生物的新机制,并为植物微生物组的操纵提供了广阔的前景。
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引用次数: 0
INDELible impact: How structural variants drive virulence and resistance INDELible影响:结构变异如何驱动毒性和抗药性
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-11-13 DOI: 10.1016/j.chom.2024.10.007
Alexandra Grote
Tuberculosis remains a formidable global health challenge, with Mycobacterium tuberculosis responsible for millions of cases and deaths annually. In this issue of Cell Host & Microbe, Worakitchanon et al. present a method to identify structural variants in Mtb and explore associations with bacterial phenotypes such as virulence and antibiotic resistance.
结核病仍然是一项严峻的全球健康挑战,结核分枝杆菌每年导致数百万人患病和死亡。在本期的《细胞宿主与amp; 微生物》(Cell Host & Microbe)杂志上,Worakitchanon 等人提出了一种方法来识别 Mtb 的结构变异,并探索其与细菌表型(如毒力和抗生素耐药性)的关联。
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引用次数: 0
Bacterial small RNA makes a big impact for gut colonization 细菌小核糖核酸对肠道定植产生重大影响
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-11-13 DOI: 10.1016/j.chom.2024.10.010
Elena Monzel, Mahesh S. Desai
The functions of non-coding small RNAs (sRNAs) within the human microbiome remain largely unexplored. In this Cell Host & Microbe issue, El Mouali et al. identify Segatella RNA colonization factor (SrcF), a sRNA from a prevalent gut bacterium Segatella copri. SrcF promotes colonization of S. copri by regulating bacterial degradation of complex dietary carbohydrates.
人类微生物组中的非编码小 RNA(sRNA)的功能在很大程度上仍未得到探索。在本期《细胞-宿主-微生物》(Cell Host & Microbe)杂志中,El Mouali 等人发现了 Segatella RNA 定殖因子(SrcF),这是一种来自肠道流行细菌 Segatella copri 的 sRNA。SrcF 通过调节细菌对复杂食物碳水化合物的降解来促进 S. copri 的定植。
{"title":"Bacterial small RNA makes a big impact for gut colonization","authors":"Elena Monzel, Mahesh S. Desai","doi":"10.1016/j.chom.2024.10.010","DOIUrl":"https://doi.org/10.1016/j.chom.2024.10.010","url":null,"abstract":"The functions of non-coding small RNAs (sRNAs) within the human microbiome remain largely unexplored. In this <em>Cell Host &amp; Microbe</em> issue, El Mouali et al. identify <em>Segatella</em> RNA colonization factor (SrcF), a sRNA from a prevalent gut bacterium <em>Segatella copri</em>. SrcF promotes colonization of <em>S. copri</em> by regulating bacterial degradation of complex dietary carbohydrates.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"2 1","pages":""},"PeriodicalIF":30.3,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A small microcin plays a big role in V. cholerae interbacterial competition 在霍乱弧菌的细菌间竞争中,一种微小的霉素发挥着重要作用
IF 30.3 1区 医学 Q1 MICROBIOLOGY Pub Date : 2024-11-13 DOI: 10.1016/j.chom.2024.10.011
Wei Peng, Kim Orth
Microcins are antibacterial small proteins secreted by gram-negative bacteria. In this issue of Cell Host & Microbe, Kim et al. report the discovery of a V. cholerae microcin, MvcC. MvcC shows antibacterial activity against non-self V. cholerae strains, which do not encode the cognate immunity protein.
微霉素是革兰氏阴性细菌分泌的抗菌小蛋白。在本期《细胞宿主与amp; 微生物》(Cell Host & Microbe)杂志上,Kim 等人报告了一种霍乱弧菌微蛋白 MvcC 的发现。MvcC 对非自身霍乱弧菌菌株具有抗菌活性,这些菌株没有编码同源免疫蛋白。
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引用次数: 0
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