Rab32 依赖性途径有助于伤寒沙门氏菌的宿主限制。
A Rab32-dependent pathway contributes to Salmonella typhi host restriction.
机构信息
Department of Microbial Pathogenesis, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.
出版信息
Science. 2012 Nov 16;338(6109):960-3. doi: 10.1126/science.1229224.
Abstract
Unlike other Salmonellae, the intracellular bacterial human pathogen Salmonella Typhi exhibits strict host specificity. The molecular bases for this restriction are unknown. Here we found that the expression of a single type III secretion system effector protein from broad-host Salmonella Typhimurium allowed Salmonella Typhi to survive and replicate within macrophages and tissues from mice, a nonpermissive host. This effector proteolytically targeted Rab32, which controls traffic to lysosome-related organelles in conjunction with components of the biogenesis of lysosome-related organelle complexes (BLOCs). RNA interference-mediated depletion of Rab32 or of an essential component of a BLOC complex was sufficient to allow S. Typhi to survive within mouse macrophages. Furthermore, S. Typhi was able to survive in macrophages from mice defective in BLOC components.
摘要
与其他沙门氏菌不同，细胞内细菌病原体伤寒沙门氏菌表现出严格的宿主特异性。这种限制的分子基础尚不清楚。在这里，我们发现来自广谱宿主沙门氏菌鼠伤寒的单个 III 型分泌系统效应蛋白的表达使伤寒沙门氏菌能够在非允许宿主的巨噬细胞和组织中存活和复制。这种效应蛋白对 Rab32 进行蛋白水解靶向，Rab32 与溶酶体相关细胞器生物发生复合物 (BLOC) 的成分一起控制到溶酶体相关细胞器的运输。RNA 干扰介导的 Rab32 或 BLOC 复合物的必需成分的耗尽足以使 S. Typhi 在小鼠巨噬细胞中存活。此外，S. Typhi 能够在 BLOC 成分缺陷的小鼠巨噬细胞中存活。
相似文献
1
A Rab32-dependent pathway contributes to Salmonella typhi host restriction.Rab32 依赖性途径有助于伤寒沙门氏菌的宿主限制。
Science. 2012 Nov 16;338(6109):960-3. doi: 10.1126/science.1229224.
2
A novel anti-microbial function for a familiar Rab GTPase.一种常见Rab GTP酶的新型抗菌功能。
Small GTPases. 2013 Oct-Dec;4(4):252-4. doi: 10.4161/sgtp.27282. Epub 2013 Dec 9.
3
A Bacterial Pathogen Targets a Host Rab-Family GTPase Defense Pathway with a GAP.一种细菌病原体通过一种GAP靶向宿主Rab家族GTPase防御途径。
Cell Host Microbe. 2016 Feb 10;19(2):216-26. doi: 10.1016/j.chom.2016.01.004.
4
Mechanisms of Salmonella Typhi Host Restriction.伤寒沙门氏菌宿主限制机制。
Adv Exp Med Biol. 2016;915:283-94. doi: 10.1007/978-3-319-32189-9_17.
5
The Rab32/BLOC-3-dependent pathway mediates host defense against different pathogens in human macrophages.Rab32/ BLOC-3依赖性途径介导人类巨噬细胞对不同病原体的宿主防御。
Sci Adv. 2021 Jan 15;7(3). doi: 10.1126/sciadv.abb1795. Print 2021 Jan.
6
Host restriction in Salmonella: insights from Rab GTPases.沙门氏菌中的宿主限制：来自Rab GTP酶的见解。
Cell Microbiol. 2014 Sep;16(9):1321-8. doi: 10.1111/cmi.12327. Epub 2014 Aug 5.
7
Rab32 restriction of intracellular bacterial pathogens.细胞内细菌性病原体的Rab32限制作用
Small GTPases. 2018 May 4;9(3):216-223. doi: 10.1080/21541248.2016.1219207. Epub 2016 Sep 20.
8
Proteolytic targeting of Rab29 by an effector protein distinguishes the intracellular compartments of human-adapted and broad-host Salmonella.效应蛋白对 Rab29 的蛋白水解靶向作用区分了人源适应和广谱宿主沙门氏菌的细胞内隔室。
Proc Natl Acad Sci U S A. 2011 Nov 8;108(45):18418-23. doi: 10.1073/pnas.1111959108. Epub 2011 Oct 31.
9
A Small-Scale shRNA Screen in Primary Mouse Macrophages Identifies a Role for the Rab GTPase Rab1b in Controlling Typhi Growth.在原代小鼠巨噬细胞中进行的小规模 shRNA 筛选鉴定出 Rab GTPase Rab1b 在控制伤寒生长中的作用。
Front Cell Infect Microbiol. 2021 Apr 7;11:660689. doi: 10.3389/fcimb.2021.660689. eCollection 2021.
10
VARP and Rab9 Are Dispensable for the Rab32/BLOC-3 Dependent Killing.VARP 和 Rab9 对于 Rab32/BLOC-3 依赖性杀伤是可有可无的。
Front Cell Infect Microbiol. 2020 Dec 16;10:581024. doi: 10.3389/fcimb.2020.581024. eCollection 2020.
引用本文的文献
1
The Rab32-LRMDA-Retriever Complex is a Key Regulator of Intestinal Immune Homeostasis.Rab32-LRMDA-回收复合物是肠道免疫稳态的关键调节因子。
bioRxiv. 2025 Jul 19:2025.07.16.665158. doi: 10.1101/2025.07.16.665158.
2
Comparative genomics of serovars Paratyphi A, Typhi and Typhimurium reveals distinct profiles of their pangenome, mobile genetic elements, antimicrobial resistance and defense systems repertoire.甲型副伤寒沙门氏菌、伤寒沙门氏菌和鼠伤寒沙门氏菌血清型的比较基因组学揭示了它们的泛基因组、可移动遗传元件、抗菌抗性和防御系统库的不同特征。
Virulence. 2025 Dec;16(1):2504658. doi: 10.1080/21505594.2025.2504658. Epub 2025 May 20.
3
Modulation of host Rab GTPases by Salmonella: mechanisms of immune evasion and intracellular replication.沙门氏菌对宿主Rab GTP酶的调控：免疫逃避和细胞内复制机制
Mol Biol Rep. 2025 Apr 30;52(1):440. doi: 10.1007/s11033-025-10547-7.
4
Rab32 regulates Golgi structure and cell migration through Protein Kinase A-mediated phosphorylation of Optineurin.Rab32通过蛋白激酶A介导的视黄醛结合蛋白磷酸化来调节高尔基体结构和细胞迁移。
Proc Natl Acad Sci U S A. 2025 Apr 29;122(17):e2502971122. doi: 10.1073/pnas.2502971122. Epub 2025 Apr 21.
5
The interplay between and host: Mechanisms and strategies for bacterial survival.细菌与宿主之间的相互作用：细菌生存的机制与策略。 （注：原文中“between”后缺少内容，根据语境推测补充完整后这样翻译更合理）
Cell Insight. 2025 Feb 13;4(2):100237. doi: 10.1016/j.cellin.2025.100237. eCollection 2025 Apr.
6
Salmonella Typhi serine threonine kinase T4519 induces lysosomal membrane permeabilization by manipulating Toll-like receptor 2-Cystatin B-Cathepsin B-NF-κB-reactive oxygen species pathway and promotes survival within human macrophages.伤寒沙门氏菌丝氨酸苏氨酸激酶T4519通过操纵Toll样受体2-胱抑素B-组织蛋白酶B-NF-κB-活性氧途径诱导溶酶体膜通透性增加，并促进其在人巨噬细胞内的存活。
PLoS Pathog. 2025 Apr 1;21(4):e1013041. doi: 10.1371/journal.ppat.1013041. eCollection 2025 Apr.
7
Type III Secretion System Effectors.III型分泌系统效应蛋白
Int J Mol Sci. 2025 Mar 14;26(6):2611. doi: 10.3390/ijms26062611.
8
Virulence factors of Salmonella Typhi: interplay between the bacteria and host macrophages.伤寒沙门氏菌的毒力因子：细菌与宿主巨噬细胞之间的相互作用
Arch Microbiol. 2025 Mar 17;207(4):89. doi: 10.1007/s00203-025-04297-0.
9
Identification of a RAB32-LRMDA-Commander membrane trafficking complex reveals the molecular mechanism of human oculocutaneous albinism type 7.一种RAB32-LRMDA-Commander膜运输复合体的鉴定揭示了7型人类眼皮肤白化病的分子机制。
bioRxiv. 2025 Feb 4:2025.02.04.636395. doi: 10.1101/2025.02.04.636395.
10
ChIP-mini: a low-input ChIP-exo protocol for elucidating DNA-binding protein dynamics in intracellular pathogens.ChIP-mini：一种用于阐明细胞内病原体中DNA结合蛋白动力学的低输入ChIP-exo方案。
Nucleic Acids Res. 2025 Jan 24;53(3). doi: 10.1093/nar/gkaf009.
本文引用的文献
1
BLOC-2, AP-3, and AP-1 proteins function in concert with Rab38 and Rab32 proteins to mediate protein trafficking to lysosome-related organelles.BLOC-2、AP-3 和 AP-1 蛋白与 Rab38 和 Rab32 蛋白协同作用，介导蛋白质运输到溶酶体相关细胞器。
J Biol Chem. 2012 Jun 1;287(23):19550-63. doi: 10.1074/jbc.M112.351908. Epub 2012 Apr 16.
2
Proteolytic targeting of Rab29 by an effector protein distinguishes the intracellular compartments of human-adapted and broad-host Salmonella.效应蛋白对 Rab29 的蛋白水解靶向作用区分了人源适应和广谱宿主沙门氏菌的细胞内隔室。
Proc Natl Acad Sci U S A. 2011 Nov 8;108(45):18418-23. doi: 10.1073/pnas.1111959108. Epub 2011 Oct 31.
3
Identification of two new loci at IL23R and RAB32 that influence susceptibility to leprosy.鉴定出影响麻风病易感性的两个新的 IL23R 和 RAB32 基因座。
Nat Genet. 2011 Oct 23;43(12):1247-51. doi: 10.1038/ng.973.
4
Salmonella effector proteins and host-cell responses.沙门氏菌效应蛋白与宿主细胞反应。
Cell Mol Life Sci. 2011 Nov;68(22):3687-97. doi: 10.1007/s00018-011-0841-0. Epub 2011 Oct 9.
5
The Salmonella enterica pan-genome.肠沙门氏菌泛基因组。
Microb Ecol. 2011 Oct;62(3):487-504. doi: 10.1007/s00248-011-9880-1. Epub 2011 Jun 4.
6
Rab GTPases regulating phagosome maturation are differentially recruited to mycobacterial phagosomes.调节吞噬体成熟的 Rab GTPases 被差异募集到分枝杆菌吞噬体上。
Traffic. 2011 Apr;12(4):407-20. doi: 10.1111/j.1600-0854.2011.01165.x. Epub 2011 Feb 21.
7
Rab protein evolution and the history of the eukaryotic endomembrane system.Rab 蛋白的进化与真核生物内膜系统的历史。
Cell Mol Life Sci. 2010 Oct;67(20):3449-65. doi: 10.1007/s00018-010-0436-1. Epub 2010 Jun 26.
8
Protein trafficking in immune cells.免疫细胞中的蛋白质运输。
Immunobiology. 2009;214(7):507-25. doi: 10.1016/j.imbio.2008.11.011.
9
So similar, yet so different: uncovering distinctive features in the genomes of Salmonella enterica serovars Typhimurium and Typhi.如此相似，却又如此不同：揭示沙门氏菌血清型鼠伤寒和伤寒的基因组中的独特特征。
FEMS Microbiol Lett. 2010 Apr;305(1):1-13. doi: 10.1111/j.1574-6968.2010.01904.x. Epub 2010 Jan 20.
10
Global trends in typhoid and paratyphoid Fever.全球伤寒和副伤寒流行趋势。
Clin Infect Dis. 2010 Jan 15;50(2):241-6. doi: 10.1086/649541.
Zotero 插件