烟曲霉尿嘧啶-尿嘧啶营养缺陷型菌株的毒力减弱
Attenuated virulence of uridine-uracil auxotrophs of Aspergillus fumigatus.
作者信息
D'Enfert C, Diaquin M, Delit A, Wuscher N, Debeaupuis J P, Huerre M, Latge J P
机构信息
Laboratoire des Aspergillus and Unité d'Histopathologie, Institut Pasteur, Paris, France.
出版信息
Infect Immun. 1996 Oct;64(10):4401-5. doi: 10.1128/iai.64.10.4401-4405.1996.
Abstract
Aspergillus fumigatus mutants that are deficient in the de novo UMP biosynthesis pathway because of a mutation in the pyrG gene encoding orotidine-5'-phosphate decarboxylase (and therefore auxotrophic for uridine or uracil) were evaluated in a murine model of invasive aspergillosis. These mutants were entirely nonpathogenic, and mutant conidia remained ungerminated in alveolar macrophages. Both the germination and virulence defects could be restored by supplementing the drinking water of the animals with uridine. DNA-mediated transformation of one of the pyrG mutants with the Aspergillus niger pyrG gene also restored virulence. These results suggest that uridine and uracil are limiting in the lung environment, thus preventing conidium germination and hence virulence of the pyrG mutants.
摘要
由于编码乳清苷 -5'-磷酸脱羧酶的pyrG基因突变而导致从头UMP生物合成途径缺陷的烟曲霉突变体（因此对尿苷或尿嘧啶营养缺陷），在侵袭性曲霉病的小鼠模型中进行了评估。这些突变体完全无致病性，并且突变体分生孢子在肺泡巨噬细胞中仍未萌发。通过在动物饮水中补充尿苷，可以恢复萌发和毒力缺陷。用黑曲霉pyrG基因对其中一个pyrG突变体进行DNA介导的转化也恢复了毒力。这些结果表明，尿苷和尿嘧啶在肺环境中是有限的，从而阻止了分生孢子的萌发，进而阻止了pyrG突变体的毒力。
相似文献
1
Attenuated virulence of uridine-uracil auxotrophs of Aspergillus fumigatus.烟曲霉尿嘧啶-尿嘧啶营养缺陷型菌株的毒力减弱
Infect Immun. 1996 Oct;64(10):4401-5. doi: 10.1128/iai.64.10.4401-4405.1996.
2
Selection of multiple disruption events in Aspergillus fumigatus using the orotidine-5'-decarboxylase gene, pyrG, as a unique transformation marker.使用乳清苷-5'-脱羧酶基因pyrG作为独特的转化标记在烟曲霉中选择多个破坏事件。
Curr Genet. 1996 Jun;30(1):76-82. doi: 10.1007/s002940050103.
3
A new and efficient approach for construction of uridine/uracil auxotrophic mutants in the filamentous fungus Aspergillus oryzae using Agrobacterium tumefaciens-mediated transformation.一种利用根癌农杆菌介导转化法构建米曲霉中尿苷/尿嘧啶营养缺陷型突变体的新型高效方法。
World J Microbiol Biotechnol. 2017 Jun;33(6):107. doi: 10.1007/s11274-017-2275-9. Epub 2017 May 2.
4
Uracil metabolism--UMP synthesis from orotic acid or uridine and conversion of uracil to beta-alanine: enzymes and cDNAs.尿嘧啶代谢——从乳清酸或尿苷合成UMP以及尿嘧啶转化为β-丙氨酸：酶和cDNA
Prog Nucleic Acid Res Mol Biol. 1996;53:1-78. doi: 10.1016/s0079-6603(08)60142-7.
5
PyrG is required for maintaining stable cellular uracil level and normal sporulation pattern under excess uracil stress in Aspergillus nidulans.在氮源饥饿条件下，PyrG 对于维持细胞内尿嘧啶水平稳定和正常的孢子形成模式是必需的。
Sci China Life Sci. 2013 May;56(5):467-75. doi: 10.1007/s11427-013-4480-6. Epub 2013 May 1.
6
An efficient Agrobacterium-mediated system based on the pyrG auxotrophic marker for recombinant expression in the filamentous fungus Penicillium rubens.基于 pyrG 营养缺陷型标记的高效农杆菌介导体系在丝状真菌玫烟色棒束孢中的重组表达。
Biotechnol Lett. 2023 Jun;45(5-6):689-702. doi: 10.1007/s10529-023-03374-y. Epub 2023 Apr 18.
7
Establishment of a new and efficient Agrobacterium-mediated transformation system in the nematicidal fungus Purpureocillium lilacinum.建立在杀线虫真菌淡紫拟青霉中新的和有效的农杆菌介导的转化系统。
Microbiol Res. 2021 Aug;249:126773. doi: 10.1016/j.micres.2021.126773. Epub 2021 Apr 26.
8
Development of a homologous transformation system for the human pathogenic fungus Aspergillus fumigatus based on the pyrG gene encoding orotidine 5'-monophosphate decarboxylase.基于编码乳清苷5'-单磷酸脱羧酶的pyrG基因开发人类致病真菌烟曲霉的同源转化系统。
Curr Genet. 1998 May;33(5):378-85. doi: 10.1007/s002940050350.
9
Avirulent uracil auxotrophs based on disruption of orotidine-5'-monophosphate decarboxylase elicit protective immunity to Toxoplasma gondii.基于乳清酸-5'-单磷酸脱羧酶的缺陷型无毒尿嘧啶营养缺陷型能够引发对刚地弓形虫的保护性免疫。
Infect Immun. 2010 Sep;78(9):3744-52. doi: 10.1128/IAI.00287-10. Epub 2010 Jul 6.
10
Profiles of pyrimidine biosynthesis, salvage and degradation in disks of potato (Solanum tuberosum L.) tubers.马铃薯（Solanum tuberosum L.）块茎圆盘嘧啶生物合成、补救和降解的概况。
Planta. 2002 Sep;215(5):821-8. doi: 10.1007/s00425-002-0806-5. Epub 2002 Jun 21.
引用本文的文献
1
Simultaneous multigene integration in Aspergillus fumigatus using CRISPR/Cas9 and endogenous counter-selectable markers.利用CRISPR/Cas9和内源性反选择标记在烟曲霉中进行多基因同时整合
J Biol Eng. 2025 Jul 28;19(1):69. doi: 10.1186/s13036-025-00539-3.
2
A genetic strategy to allow detection of F-actin by phalloidin staining in diverse fungi.一种通过鬼笔环肽染色在多种真菌中检测丝状肌动蛋白的遗传策略。
bioRxiv. 2025 May 1:2025.04.29.651289. doi: 10.1101/2025.04.29.651289.
3
A Pilot Metabolomic Study for Diagnosing Infection in Immunocompromised Pediatric Cancer Patients.一项用于诊断免疫功能低下的儿科癌症患者感染的代谢组学初步研究。
Int J Mol Sci. 2025 Jun 20;26(13):5926. doi: 10.3390/ijms26135926.
4
PWWP domain-containing protein Crf4-3 specifically modulates fungal azole susceptibility by regulating sterol C-14 demethylase ERG11.含PWWP结构域的蛋白Crf4-3通过调节甾醇C-14脱甲基酶ERG11特异性地调控真菌对唑类药物的敏感性。
mSphere. 2025 Jan 28;10(1):e0070324. doi: 10.1128/msphere.00703-24. Epub 2024 Dec 13.
5
Alternative ergosterol biosynthetic pathways confer antifungal drug resistance in the human pathogens within the species complex.种复合体中的人类病原体中，替代麦角固醇生物合成途径赋予了抗真菌药物耐药性。
mBio. 2024 Aug 14;15(8):e0166124. doi: 10.1128/mbio.01661-24. Epub 2024 Jul 9.
6
Sirtuin E deacetylase is required for full virulence of Aspergillus fumigatus.Sirtuin E 去乙酰化酶是烟曲霉完全毒力所必需的。
Commun Biol. 2024 Jun 8;7(1):704. doi: 10.1038/s42003-024-06383-3.
7
Role of the Gene in Development, Secondary Metabolism and Virulence.该基因在发育、次生代谢和毒力中的作用。
J Fungi (Basel). 2024 Jan 26;10(2):103. doi: 10.3390/jof10020103.
8
Development of a murine model to study the cerebral pathogenesis of .建立一个研究 …… 的脑部发病机制的小鼠模型。
mSphere. 2023 Dec 20;8(6):e0046823. doi: 10.1128/msphere.00468-23. Epub 2023 Nov 27.
9
NIH4215: A mutation-prone thiamine auxotrophic clinical isolate.NIH4215：一种易于发生突变的硫胺素营养缺陷型临床分离株。
Front Fungal Biol. 2022 Jul 25;3:908343. doi: 10.3389/ffunb.2022.908343. eCollection 2022.
10
Development of Marker Recycling Systems for Sequential Genetic Manipulation in Marine-Derived Fungi sp. SCSIO F190 and sp. SCSIO SX7S7.用于海洋来源真菌sp. SCSIO F190和sp. SCSIO SX7S7中连续基因操作的标记回收系统的开发
J Fungi (Basel). 2023 Feb 26;9(3):302. doi: 10.3390/jof9030302.
本文引用的文献
1
A stain for fungi in tissue sections and smears using Gomori's methenamine-silver nitrate technic.一种使用戈莫里甲萘胺银硝酸盐技术对组织切片和涂片进行真菌染色的方法。
Am J Clin Pathol. 1955 Aug;25(8):975-9. doi: 10.1093/ajcp/25.8_ts.0975.
2
Selection of multiple disruption events in Aspergillus fumigatus using the orotidine-5'-decarboxylase gene, pyrG, as a unique transformation marker.使用乳清苷-5'-脱羧酶基因pyrG作为独特的转化标记在烟曲霉中选择多个破坏事件。
Curr Genet. 1996 Jun;30(1):76-82. doi: 10.1007/s002940050103.
3
The alkaline protease of Aspergillus fumigatus is not a virulence determinant in two murine models of invasive pulmonary aspergillosis.烟曲霉的碱性蛋白酶在两种侵袭性肺曲霉病小鼠模型中并非毒力决定因素。
Infect Immun. 1993 May;61(5):1650-6. doi: 10.1128/iai.61.5.1650-1656.1993.
4
Selection of bacterial virulence genes that are specifically induced in host tissues.在宿主组织中特异性诱导表达的细菌毒力基因的筛选。
Science. 1993 Jan 29;259(5095):686-8. doi: 10.1126/science.8430319.
5
Virulence of alkaline protease-deficient mutants of Aspergillus fumigatus.烟曲霉碱性蛋白酶缺陷型突变体的毒力
FEMS Microbiol Lett. 1993 Jan 1;106(1):39-46. doi: 10.1111/j.1574-6968.1993.tb05932.x.
6
Virulence studies of Aspergillus nidulans mutants requiring lysine or p-aminobenzoic acid in invasive pulmonary aspergillosis.在侵袭性肺曲霉病中对需要赖氨酸或对氨基苯甲酸的构巢曲霉突变体的毒力研究。
Infect Immun. 1994 Dec;62(12):5255-60. doi: 10.1128/iai.62.12.5255-5260.1994.
7
Antibiotic-based selection for bacterial genes that are specifically induced during infection of a host.基于抗生素对宿主感染期间特异性诱导的细菌基因进行筛选。
Proc Natl Acad Sci U S A. 1995 Jan 31;92(3):669-73. doi: 10.1073/pnas.92.3.669.
8
Cloning and disruption of the gene encoding an extracellular metalloprotease of Aspergillus fumigatus.烟曲霉细胞外金属蛋白酶编码基因的克隆与破坏
Mol Microbiol. 1994 Dec;14(5):917-28. doi: 10.1111/j.1365-2958.1994.tb01327.x.
9
Avirulence of Candida albicans auxotrophic mutants in a rat model of oropharyngeal candidiasis.白色念珠菌营养缺陷型突变体在大鼠口腔念珠菌病模型中的无毒力
FEMS Microbiol Lett. 1995 Feb 15;126(2):177-80. doi: 10.1111/j.1574-6968.1995.tb07413.x.
10
Selective protection against conidia by mononuclear and against mycelia by polymorphonuclear phagocytes in resistance to Aspergillus. Observations on these two lines of defense in vivo and in vitro with human and mouse phagocytes.在对曲霉的抗性中，单核吞噬细胞对分生孢子具有选择性保护作用，多形核吞噬细胞对菌丝体具有选择性保护作用。用人和小鼠吞噬细胞在体内和体外对这两种防御机制的观察。
J Clin Invest. 1982 Mar;69(3):617-31. doi: 10.1172/jci110489.
Zotero 插件