分枝杆菌T7SS (ESX)分泌系统功能研究进展

doi:10.16288/j.yczz.23-188

遗传 ›› 2023, Vol. 45 ›› Issue (12): 1100-1113.doi: 10.16288/j.yczz.23-188

分枝杆菌T7SS (ESX)分泌系统功能研究进展

蒋智勇(), 谢建平()

西南大学生命科学学院现代生物医药研究所，重庆 400715

收稿日期:2023-07-10 修回日期:2023-09-12 出版日期:2023-12-20 发布日期:2023-09-18
通讯作者: 谢建平 E-mail:2287834994@qq.com;georgex@swu.edu.cn
作者简介:蒋智勇，硕士研究生，专业方向：微生物遗传学与感染免疫。E-mail: 2287834994@qq.com
基金资助:
国家自然科学基金项目(4112000164)

Progress on the function of Mycobacterium T7SS (ESX) secretion system

Zhiyong Jiang(), Jianping Xie()

Institute of Modern Biopharmaceuticals, School of Life Sciences, Southwest University, Chongqing 400715, China

Received:2023-07-10 Revised:2023-09-12 Published:2023-12-20 Online:2023-09-18
Contact: Jianping Xie E-mail:2287834994@qq.com;georgex@swu.edu.cn
Supported by:
National Natural Science Foundation of China(4112000164)

摘要/Abstract

摘要：

分枝杆菌感染宿主后能够通过分泌至胞外的效应蛋白去影响宿主的免疫功能，其中ESX (或VII型)系统在效应蛋白分泌方面发挥了重要作用。ESX分泌系统是分枝杆菌和许多放线菌中的蛋白质输出系统，但目前ESX系统如何将底物运输穿过外膜的分子机制以及调控机制尚不清楚。本文对ESX系统的组成、功能、分类以及将底物运输至周质空间的相关研究进展展开了综述，并探讨了ESX系统在抗生素耐药、持留及与宿主-噬菌体相互作用中的功能，以及作为新药物靶标的潜力，以期为结核病新药物和疫苗抗原的发现提供新的见解。

关键词: ESX系统, 分枝杆菌, 膜复合体, 抗生素, 毒力因子

Abstract:

Mycobacterium infection can affect the host’s immune function by secreting extracellular effector proteins. ESX (or type VII) system plays an important role in the secretion of effector proteins. ESX system is the protein export system in mycobacteria and many actinomycetes. However, how ESX system secretes and underlying mechanism of action remain unclear. In this review, we introduce the components, function, classification of ESX system and the process of substrates transfer to the peripheral space via this system, and discuss the roles of ESX system in antibiotics resistance, persistence, host-phage interaction, new drug targets. We hope to provide insights into the discovery of new drugs and vaccine antigens for tuberculosis.

Key words: ESX system, Mycobacterium, membrane complex, antibiotic, virulence factor

蒋智勇, 谢建平. 分枝杆菌T7SS (ESX)分泌系统功能研究进展[J]. 遗传, 2023, 45(12): 1100-1113.

Zhiyong Jiang, Jianping Xie. Progress on the function of Mycobacterium T7SS (ESX) secretion system[J]. Hereditas(Beijing), 2023, 45(12): 1100-1113.

图/表 7

表1

不同ESX系统的组分"

ESX系统亚型	组分	H37Rv中编号	功能预测	缺失效应
ESX-1	EccA1	Rv3868	调节分枝杆菌枝菌酸的合成速率	在原代小鼠巨噬细胞中存活所需
	EccB1	Rv3869	膜复合体结构蛋白	在C57BL/6J小鼠脾脏中生长所需
	EccCa	Rv3870	膜复合体结构蛋白	结核分枝杆菌H37Rv Rv3870突变株的生长和细胞毒性减弱
	EccCb	Rv3871	膜复合体结构蛋白	减弱了结核分枝杆菌H37Rv的毒性
	EccD1	Rv3877	膜复合体结构蛋白	在C57BL/6J小鼠脾脏中生长所需，减弱了结核分枝杆菌H37Rv的毒性
	EccE1	Rv3882c	膜复合体结构蛋白	在C57BL/6J小鼠脾脏中生长所需，减弱了结核分枝杆菌H37Rv的毒性
	MycP1	Rv3883c	膜复合体结构蛋白，丝氨酸激酶	导致EsxA无法分泌，减弱了在BALB/c小鼠中的毒性
ESX-2	EccB2	Rv3895c	膜复合体结构蛋白
	EccC2	Rv3894c	膜复合体结构蛋白
	EccD2	Rv3887c	膜复合体结构蛋白
	MycP2	Rv3886c	膜复合体结构蛋白，丝氨酸激酶
	EccE2	Rv3885c	膜复合体结构蛋白
	EccA2	Rv3884c	AAA+家组蛋白(多种细胞活动相关的ATP酶)
ESX-3	EccA3	Rv0282	AAA+家组蛋白(多种细胞活动相关的ATP酶)
	EccB3	Rv0283	膜复合体结构蛋白	体外无法正常生长
	EccC3	Rv0284	膜复合体结构蛋白	体外无法正常生长
	EccD3	Rv0290	膜复合体结构蛋白	体外无法正常生长
	MycP3	Rv0291	膜复合体结构蛋白，丝氨酸激酶	体外无法正常生长
	EccE3	Rv0292	膜复合体结构蛋白	体外无法正常生长
ESX-4	EccB4	Rv3450c	膜复合体结构蛋白
	MycP4	Rv3449	膜复合体结构蛋白，丝氨酸激酶
	EccD4	Rv3448	膜复合体结构蛋白
	EccC4	Rv3447c	膜复合体结构蛋白
ESX-5	EccB5	Rv1782	膜复合体结构蛋白	体外生长缺陷
	EccC5	Rv1783	膜复合体结构蛋白	体外生长缺陷
	EccD5	Rv1795	膜复合体结构蛋白	体外生长缺陷
	MycP5	Rv1796	膜复合体结构蛋白，丝氨酸激酶	体外生长缺陷
	EccE5	Rv1797	膜复合体结构蛋白	体外生长缺陷
	EccA5	Rv1798	AAA+家族组蛋白(多种细胞活动相关的ATP酶)	在胆固醇为单一碳源的培养基上无法生长

表1

表2

不同ESX系统的底物"

ESX系统亚型	底物	H37Rv中编号	功能预测	缺失效应
ESX-1	EspG1	Rv3866	PE/PPE的分子伴侣	影响PE/PPE蛋白的分泌
	EspH	Rv3867	Esp底物的分子伴侣	在斑马鱼幼体中，敲除EspH显著增加了海分枝杆菌的毒力
	EspE	Rv3864	与EspF形成异源二聚体，可能与外膜上形成的孔道相关，调控ESX-1系统底物的表达	影响海分枝杆菌的溶血活性，在C57BL/6J小鼠脾脏中生长所需
	EspF	Rv3865	与EspE形成异源二聚体，可能与外膜上形成的孔道相关，调控ESX-1系统底物的表达	影响海分枝杆菌的溶血活性，在C57BL/6J小鼠脾脏中生长所需
	PE35	Rv3872	与PPE68形成异源二聚体	在C57BL/6J小鼠脾脏中生长所需
	PPE68	Rv3873	与PE35形成异源二聚体	在C57BL/6J小鼠脾脏中生长所需
	EsxA	Rv3875	与EsxB形成异源二聚体，毒力因子，破裂吞噬体膜	细菌生长受阻以及毒性减弱
	EsxB	Rv3874	与EsxA形成异源二聚体，毒力因子，破裂吞噬体膜	细菌生长受阻以及毒性减弱
	EspI	Rv3876	影响分枝杆菌胞内ATP水平	细菌生长受阻以及毒性减弱
	EspJ	Rv3878	促进细菌在宿主体内的存活
	EspL	Rv3880c	与EsxA和EspE的分泌相关
	EspK	Rv3879c	EspB的分子伴侣
	EspB	Rv3881c	被MycP1切割裂解，并且能形成7聚物的疏水圆环插入细胞膜中
ESX-2	EspG2	Rv3889c	PE/PPE的分子伴侣
	Rv3888c	Rv3888c	保守的膜蛋白	体外生长缺陷
	PE36	Rv3893c	与PPE69形成异源二聚体
	PPE69	Rv3892c	与PE36形成异源二聚体
	EsxD	Rv3891c	Esx类蛋白，与EsxC形成异源二聚体
	EsxC	Rv3890c	Esx类蛋白，与EsxD形成异源二聚体	多出现在临床
ESX-3	EspG3	Rv0289	PE/PPE的分子伴侣
	PE5	Rv0285	与PPE4形成异源二聚体	体外生长缺陷
	PPE4	Rv0286	与PE5形成异源二聚体	体外生长缺陷
	EsxG	Rv0287	影响宿主吞噬体膜的修复	体外生长缺陷
	EsxH	Rv0288	影响宿主吞噬体膜的修复	体外生长缺陷
	Rv3446	Rv3446
ESX-4	EsxU	Rv3445c	影响了细菌在宿主体内的存活与持留
ESX-4	EsxT	Rv3444c	影响了细菌在宿主体内的存活与持留
ESX-5	Rv1785	Rv1785	参与中间代谢和氧化呼吸
	Rv1786	Rv1786	铁氧还蛋白，参与中间代谢和氧化呼吸
	PPE25	Rv1787	与pe19形成异源二聚体	有助于体外生长
	PE18	Rv1788	形成中性粒细胞胞外陷阱	有助于体外生长
	PPE26	Rv1789	促进了细菌在宿主体内的存活	有助于体外生长
	PPE27	Rv1790	促进了细菌在宿主体内的存活	有助于体外生长
	PE19	Rv1791	促进了细菌在宿主体内的存活，与PPE25形成异源二聚体
	EsxM	Rv1792	促进了肉芽肿的形成
	EsxN	Rv1793	促进了肉芽肿的形成
	EspG5	Rv1794	PE/PPE的分子伴侣	体外生长缺陷

表2

图1

表3

图2

表4

图3

参考文献 47

[1]	Stanley SA, Raghavan S, Hwang WW, Cox JS. Acute infection and macrophage subversion by Mycobacterium tuberculosis require a specialized secretion system. Proc Natl Acad Sci USA, 2003, 100(22): 13001-13006. pmid: 14557536
[2]	Bunduc CM, Bitter W, Houben ENG. Structure and function of the mycobacterial type VII secretion systems. Annu Rev Microbiol, 2020, 74: 315-335. doi: 10.1146/annurev-micro-012420-081657 pmid: 32660388
[3]	Gröschel MI, Sayes F, Simeone R, Majlessi L, Brosch R. ESX secretion systems: mycobacterial evolution to counter host immunity. Nat Rev Microbiol, 2016, 14(11): 677-691. doi: 10.1038/nrmicro.2016.131 pmid: 27665717
[4]	Newton-Foot M, Warren RM, Sampson SL, van Helden PD, Gey van Pittius NC. The plasmid-mediated evolution of the mycobacterial ESX (Type VII) secretion systems. BMC Evol Biol, 2016, 16: 62. doi: 10.1186/s12862-016-0631-2 pmid: 26979252
[5]	Houben D, Demangel C, van Ingen J, Perez J, Baldeon L, Abdallah AM, Caleechurn L, Bottai D, van Zon M, de Punder K, van der Laan T, Kant A, Bossers-de Vries R, Willemsen P, Bitter W, van Soolingen D, Brosch R, van der Wel N, Peters PJ. ESX-1-mediated translocation to the cytosol controls virulence of mycobacteria. Cell Microbiol, 2012, 14(8): 1287-1298. doi: 10.1111/j.1462-5822.2012.01799.x pmid: 22524898
[6]	Lienard J, Nobs E, Lovins V, Movert E, Valfridsson C, Carlsson F. The Mycobacterium marinum ESX-1 system mediates phagosomal permeabilization and type I interferon production via separable mechanisms. Proc Natl Acad Sci USA, 2020, 117(2): 1160-1166. doi: 10.1073/pnas.1911646117 pmid: 31879349
[7]	Osman MM, Pagan AJ, Shanahan JK, Ramakrishnan L. Mycobacterium marinum phthiocerol dimycocerosates enhance macrophage phagosomal permeabilization and membrane damage. PLoS One, 2020, 15(7): e0233252. doi: 10.1371/journal.pone.0233252
[8]	Gray TA, Clark RR, Boucher N, Lapierre P, Smith C, Derbyshire KM. Intercellular communication and conjugation are mediated by ESX secretion systems in mycobacteria. Science, 2016, 354(6310): 347-350. pmid: 27846571
[9]	Ates LS. New insights into the mycobacterial PE and PPE proteins provide a framework for future research. Mol Microbiol, 2020, 113(1): 4-21. doi: 10.1111/mmi.14409 pmid: 31661176
[10]	Bychenko O, Skvortsova Y, Ziganshin R, Grigorov A, Aseev L, Ostrik A, Kaprelyants A, Salina EG, Azhikina T. Mycobacterium tuberculosis small RNA MTS1338 confers pathogenic properties to non-pathogenic Mycobacterium smegmatis. Microorganisms, 2021, 9(2): 414. doi: 10.3390/microorganisms9020414
[11]	Nath Y, Ray SK, Buragohain AK. Essential role of the ESX-3 associated eccD3 locus in maintaining the cell wall integrity of Mycobacterium smegmatis. Int J Med Microbiol, 2018, 308(7): 784-795. doi: S1438-4221(18)30086-9 pmid: 30257807
[12]	Wang YC, Tang YT, Lin C, Zhang JL, Mai JT, Jiang J, Gao XX, Li Y, Zhao GP, Zhang L, Liu J. Crosstalk between the ancestral type VII secretion system ESX-4 and other T7SS in Mycobacterium marinum. iScience, 2022, 25(1): 103585. doi: 10.1016/j.isci.2021.103585
[13]	White DW, Elliott SR, Odean E, Bemis LT, Tischler AD. Mycobacterium tuberculosis Pst/SenX3-RegX3 regulates membrane vesicle production independently of ESX-5 activity. mBio, 2018, 9(3): e00778.
[14]	Ates LS, Ummels R, Commandeur S, van de Weerd R, Sparrius M, Weerdenburg E, Alber M, Kalscheuer R, Piersma SR, Abdallah AM, Abd El Ghany M, Abdel-Haleem AM, Pain A, Jiménez CR, Bitter W, Houben ENG. Essential role of the ESX-5 secretion system in outer membrane permeability of pathogenic mycobacteria. PLoS Genet, 2015, 11(5): e1005190. doi: 10.1371/journal.pgen.1005190
[15]	Bottai D, Di Luca M, Majlessi L, Frigui W, Simeone R, Sayes F, Bitter W, Brennan MJ, Leclerc C, Batoni G, Campa M, Brosch R, Esin S. Disruption of the ESX-5 system of Mycobacterium tuberculosis causes loss of PPE protein secretion, reduction of cell wall integrity and strong attenuation. Mol Microbiol, 2012, 83(6): 1195- 1209. doi: 10.1111/j.1365-2958.2012.08001.x pmid: 22340629
[16]	Tiwari S, Dutt TS, Chen B, Chen M, Kim J, Dai AZ, Lukose R, Shanley C, Fox A, Karger BR, Porcelli SA, Chan J, Podell BK, Obregon-Henao A, Orme IM, Jacobs WR Jr, Henao-Tamayo M.BCG-Prime and boost with Esx-5 secretion system deletion mutant leads to better protection against clinical strains of Mycobacterium tuberculosis. Vaccine, 2020, 38(45): 7156-7165. doi: 10.1016/j.vaccine.2020.08.004 pmid: 32978002
[17]	Chirakos AE, Nicholson KR, Huffman A, Champion PA. Conserved ESX-1 substrates EspE and EspF are virulence factors that regulate gene expression. Infect Immun, 2020, 88(12): e00289-20.
[18]	Solomonson M, Setiaputra D, Makepeace KAT, Lameignere E, Petrotchenko EV, Conrady DG, Bergeron JR, Vuckovic M, DiMaio F, Borchers CH, Yip CK, Strynadka NCJ. Structure of EspB from the ESX-1 type VII secretion system and insights into its export mechanism. Structure, 2015, 23(3): 571-583. doi: S0969-2126(15)00003-9 pmid: 25684576
[19]	Abdallah AM, Weerdenburg EM, Guan QT, Ummels R, Borggreve S, Adroub SA, Malas TB, Naeem R, Zhang HM, Otto TD, Bitter W, Pain A. Integrated transcriptomic and proteomic analysis of pathogenic mycobacteria and their esx-1 mutants reveal secretion-dependent regulation of ESX-1 substrates and WhiB6 as a transcriptional regulator. PLoS One, 2019, 14(1): e0211003. doi: 10.1371/journal.pone.0211003
[20]	Bitter W, Houben EN, Bottai D, Brodin P, Brown EJ, Cox JS, Derbyshire K, Fortune SM, Gao LY, Liu J, Gey van Pittius NC, Pym AS, Rubin EJ, Sherman DR, Cole ST, Brosch R. Systematic genetic nomenclature for type VII secretion systems. PLoS Pathog, 2009, 5(10): e1000507. doi: 10.1371/journal.ppat.1000507
[21]	Tuukkanen AT, Freire D, Chan S, Arbing MA, Reed RW, Evans TJ, Zenkeviciute G, Kim J, Kahng S, Sawaya MR, Chaton CT, Wilmanns M, Eisenberg D, Parret AHA, Korotkov KV. Structural variability of EspG chaperones from mycobacterial ESX-1, ESX-3, and ESX-5 type VII secretion systems. J Mol Biol, 2019, 431(2): 289-307. doi: S0022-2836(18)30423-6 pmid: 30419243
[22]	Phan TH, van Leeuwen LM, Kuijl C, Ummels R, van Stempvoort G, Rubio-Canalejas A, Piersma SR, Jiménez CR, van der Sar AM, Houben ENG, Bitter W. EspH is a hypervirulence factor for Mycobacterium marinum and essential for the secretion of the ESX-1 substrates EspE and EspF. PLoS Pathog, 2018, 14(8): e1007247. doi: 10.1371/journal.ppat.1007247
[23]	Bunduc CM, Fahrenkamp D, Wald J, Ummels R, Bitter W, Houben ENG, Marlovits TC. Structure and dynamics of a mycobacterial type VII secretion system. Nature, 2021, 593(7859): 445-448. doi: 10.1038/s41586-021-03517-z
[24]	Poweleit N, Czudnochowski N, Nakagawa R, Trinidad DD, Murphy KC, Sassetti CM, Rosenberg OS. The structure of the endogenous ESX-3 secretion system. Elife, 2019, 8: e52983. doi: 10.7554/eLife.52983
[25]	Beckham KS, Ciccarelli L, Bunduc CM, Mertens HD, Ummels R, Lugmayr W, Mayr J, Rettel M, Savitski MM, Svergun DI, Bitter W, Wilmanns M, Marlovits TC, Parret AHA, Houben ENG. Structure of the mycobacterial ESX-5 type VII secretion system membrane complex by single-particle analysis. Nat Microbiol, 2017, 2: 17047. doi: 10.1038/nmicrobiol.2017.47 pmid: 28394313
[26]	Rivera-Calzada A, Famelis N, Llorca O, Geibel S. Type VII secretion systems: structure, functions and transport models. Nat Rev Microbiol, 2021, 19(9): 567-584. doi: 10.1038/s41579-021-00560-5 pmid: 34040228
[27]	Tak U, Dokland T, Niederweis M. Pore-forming Esx proteins mediate toxin secretion by Mycobacterium tuberculosis. Nat Commun, 2021, 12(1): 394. doi: 10.1038/s41467-020-20533-1 pmid: 33452244
[28]	Frigui W, Bottai D, Majlessi L, Monot M, Josselin E, Brodin P, Garnier T, Gicquel B, Martin C, Leclerc C, Cole ST, Brosch R. Control of M. tuberculosis ESAT-6 secretion and specific T cell recognition by PhoP. PLoS Pathog, 2008, 4(2): e33. doi: 10.1371/journal.ppat.0040033
[29]	Cao GX, Howard ST, Zhang PP, Wang XS, Chen XL, Samten B, Pang XH. EspR, a regulator of the ESX-1 secretion system in Mycobacterium tuberculosis, is directly regulated by the two-component systems MprAB and PhoPR. Microbiology (Reading), 2015, 161(Pt 3): 477-489. doi: 10.1099/mic.0.000023 pmid: 25536998
[30]	Boshoff HI, Myers TG, Copp BR, McNeil MR, Wilson MA, Barry CE 3rd. The transcriptional responses of Mycobacterium tuberculosis to inhibitors of metabolism: novel insights into drug mechanisms of action. J Biol Chem, 2004, 279(38): 40174-40184. doi: 10.1074/jbc.M406796200 pmid: 15247240
[31]	Ioerger TR, O'Malley T, Liao RL, Guinn KM, Hickey MJ, Mohaideen N, Murphy KC, Boshoff HI, Mizrahi V, Rubin EJ, Sassetti CM, Barry CE 3rd, Sherman DR, Parish T, Sacchettini JC. Identification of new drug targets and resistance mechanisms in Mycobacterium tuberculosis. PLoS One, 2013, 8(9): e75245. doi: 10.1371/journal.pone.0075245
[32]	Rybniker J, Chen JM, Sala C, Hartkoorn RC, Vocat A, Benjak A, Boy-Röttger S, Zhang M, Székely R, Greff Z, Orfi L, Szabadkai I, Pató J, Kéri G, Cole ST. Anticytolytic screen identifies inhibitors of mycobacterial virulence protein secretion. Cell Host Microbe, 2014, 16(4): 538-548. doi: 10.1016/j.chom.2014.09.008 pmid: 25299337
[33]	Chatterjee A, Willett JLE, Dunny GM, Duerkop BA. Phage infection and sub-lethal antibiotic exposure mediate Enterococcus faecalis type VII secretion system dependent inhibition of bystander bacteria. PLoS Genet, 2021, 17(1): e1009204. doi: 10.1371/journal.pgen.1009204
[34]	Cushman J, Freeman E, McCallister S, Schumann A, Hutchison KW, Molloy SD. Increased whiB7 expression and antibiotic resistance in Mycobacterium chelonae carrying two prophages. BMC Microbiol, 2021, 21(1): 176. doi: 10.1186/s12866-021-02224-z pmid: 34107872
[35]	Bernard EM, Fearns A, Bussi C, Santucci P, Peddie CJ, Lai RJ, Collinson LM, Gutierrez MG. M. tuberculosis infection of human iPSC-derived macrophages reveals complex membrane dynamics during xenophagy evasion. J Cell Sci, 2020, 134(5): jcs252973.
[36]	Huang TY, Irene D, Zulueta MM, Tai TJ, Lain SH, Cheng CP, Tsai PX, Lin SY, Chen ZG, Ku CC, Hsiao CD, Chyan CL, Hung SC. Structure of the complex between a heparan sulfate octasaccharide and mycobacterial heparin-binding hemagglutinin. Angew Chem Int Ed Engl, 2017, 56(15): 4192-4196. doi: 10.1002/anie.v56.15
[37]	Hinman AE, Jani C, Pringle SC, Zhan WR, Jain N, Martinot AJ, Barczak AK. Mycobacterium tuberculosis canonical virulence factors interfere with a late component of the TLR2 response. Elife, 2021, 10: e73984. doi: 10.7554/eLife.73984
[38]	López-Jiménez AT, Cardenal-Muñoz E, Leuba F, Gerstenmaier L, Barisch C, Hagedorn M, King JS, Soldati T. The ESCRT and autophagy machineries cooperate to repair ESX-1-dependent damage at the Mycobacterium- containing vacuole but have opposite impact on containing the infection. PLoS Pathog, 2018, 14(12): e1007501. doi: 10.1371/journal.ppat.1007501
[39]	Kim YS, Yang CS, Nguyen LT, Kim JK, Jin HS, Choe JH, Kim SY, Lee HM, Jung M, Kim JM, Kim MH, Jo EK, Jang JC. Mycobacterium abscessus ESX-3 plays an important role in host inflammatory and pathological responses during infection. Microbes Infect, 2017, 19(1): 5-17. doi: 10.1016/j.micinf.2016.09.001
[40]	Mehra A, Zahra A, Thompson V, Sirisaengtaksin N, Wells A, Porto M, Köster S, Penberthy K, Kubota Y, Dricot A, Rogan D, Vidal M, Hill DE, Bean AJ, Philips JA. Mycobacterium tuberculosis type VII secreted effector EsxH targets host ESCRT to impair trafficking. PLoS Pathog, 2013, 9(10): e1003734. doi: 10.1371/journal.ppat.1003734
[41]	Heijmenberg I, Husain A, Sathkumara HD, Muruganandah V, Seifert J, Miranda-Hernandez S, Kashyap RS, Field MA, Krishnamoorthy G, Kupz A. ESX-5-targeted export of ESAT-6 in BCG combines enhanced immunogenicity & efficacy against murine tuberculosis with low virulence and reduced persistence. Vaccine, 2021, 39(50): 7265-7276. doi: 10.1016/j.vaccine.2021.08.030 pmid: 34420788
[42]	Mi YJ, Bao L, Gu DQ, Luo T, Sun CF, Yang GP. Mycobacterium tuberculosis PPE25 and PPE26 proteins expressed in Mycobacterium smegmatis modulate cytokine secretion in mouse macrophages and enhance mycobacterial survival. Res Microbiol, 2017, 168(3): 234-243. doi: 10.1016/j.resmic.2016.06.004
[43]	Yang GP, Luo T, Sun CF, Yuan JN, Peng X, Zhang CX, Zhai XQ, Bao L. PPE27 in mycobacterium smegmatis enhances mycobacterial survival and manipulates cytokine secretion in mouse macrophages. J Interferon Cytokine Res, 2017, 37(9): 421-431. doi: 10.1089/jir.2016.0126
[44]	Singh V, Jamwal S, Jain R, Verma P, Gokhale R, Rao KVS. Mycobacterium tuberculosis-driven targeted recalibration of macrophage lipid homeostasis promotes the foamy phenotype. Cell Host Microbe, 2012, 12(5): 669-681. doi: 10.1016/j.chom.2012.09.012 pmid: 23159056
[45]	Tucci P, Portela M, Chetto CR, González-Sapienza G, Marín M. Integrative proteomic and glycoproteomic profiling of Mycobacterium tuberculosis culture filtrate. PLoS One, 2020, 15(3): e0221837. doi: 10.1371/journal.pone.0221837
[46]	Immanuel SRC, Arrieta-Ortiz ML, Ruiz RA, Pan M, Lopez Garcia de Lomana A, Peterson EJR, Baliga NS. Quantitative prediction of conditional vulnerabilities in regulatory and metabolic networks using PRIME. NPJ Syst Biol Appl, 2021, 7(1): 43. doi: 10.1038/s41540-021-00205-6 pmid: 34873198
[47]	Van den Bossche A, Varet H, Sury A, Sismeiro O, Legendre R, Coppee JY, Mathys V, Ceyssens PJ. Transcriptional profiling of a laboratory and clinical Mycobacterium tuberculosis strain suggests respiratory poisoning upon exposure to delamanid. Tuberculosis (Edinb), 2019, 117: 18-23. doi: 10.1016/j.tube.2019.05.002

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抗生素	抗生素英文名	作用机理
新生霉素	Novobiocin	抑制细菌细胞壁的合成，使细菌迅速破裂溶解
异烟肼	INH(isoniazid)	抑制结核菌菌壁枝菌酸的合成，扰动电子传递链，影响ATP的产生
5-氯吡嗪酰胺	X5CL_PZA	能抑制脂肪酸合成酶I(FAS-I)的活性
PA824	PA824	主要通过抑制细菌蛋白质合成和细胞壁枝菌酸合成的双重机制达到抑制结核分枝杆菌的效果
戊脉安	Verapamil	钙拮抗剂
缬氨霉素	Valinomycin	选择性地与K⁺离子结合形成脂溶性复合物，使K+容易得通过膜脂双层，呼吸链离子载体抑制剂，通过增加线粒体内膜对K⁺的通透性，抑制氧化磷酸化作用
氯法齐明	Clofazimine	干扰核酸代谢，抑制菌体蛋白合成
四环素	Tet(Tetracycline)	阻止氨酰基与核糖核蛋白体的结合，阻止肽链的增长和蛋白质的合成，从而抑制细菌的生长
阿米卡星	Amikacin	作用于细菌体内的核糖体，抑制细菌蛋白质合成，并破坏细菌细胞壁的完整性，致使细菌细胞膜破坏，细胞死亡
卷曲霉素	Cap(capreomycin)	干扰核糖体30S的形成，抑制细菌的生长
罗红霉素	Rox(roxithromycin)	与细菌50S核糖体亚基结合，通过阻断转肽作用和mRNA移位而抑制细菌蛋白质的合成，从而起抗菌作用

结核分枝杆菌基因	龟分枝杆菌基因	log₂FC	变化	结核分枝杆菌基因	龟分枝杆菌基因	log₂FC	变化
mas	BB28_RS22650	3.25	上调	ppsC	BB28_RS21210	2.07	上调
nrp	BB28_RS03915	3.64	上调	ppsA	BB28_RS04270	2.52	上调
carB	BB28_RS04260	3.87	上调	fas	BB28_RS21245	2.13	上调
mbtB	BB28_RS19005	5.32	上调	moxR2	BB28_RS01885	-3.18	下调
pks5	BB28_RS06235	2.96	上调	ligA	BB28_RS01850	-3.13	下调
fabG1	BB28_RS13295	-2.32	下调	cobN	BB28_RS10315	2.11	上调
dnaE1	BB28_RS01845	-4.76	下调	eccB1	BB28_RS03465	2.95	上调
fadD9	BB28_RS05390	4.14	上调

分枝杆菌T7SS (ESX)分泌系统功能研究进展

Progress on the function of Mycobacterium T7SS (ESX) secretion system

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[6]	杨盛智, 吴国艳, 龙梅, 邓雯文, 王红宁, 邹立扣. 鸡蛋生产链中沙门氏菌对抗生素及消毒剂的耐药性研究[J]. 遗传, 2016, 38(10): 948-956.
[7]	刘洋, 王邦兴, 刘志永, 韩轶, 谭耀驹, 李昕洁, 刘健雄, 谭守勇, 张天宇. 非一线抗结核药物耐药机制及耐药性诊断研究进展[J]. 遗传, 2016, 38(10): 928-939.
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[10]	崔鹏, 许涛, 张文宏, 张颖. 细菌持留与抗生素表型耐药机制[J]. 遗传, 2016, 38(10): 859-871.
[11]	樊祥宇, 何颖, 谢建平. 以分枝杆菌噬菌体为例探索生命科学研究型教学[J]. 遗传, 2014, 36(8): 842-846.
[12]	彭光华，郑斌娇，方芳，伍越，梁玲芝，郑静，南奔宇，余啸，唐霄雯，朱翌，吕建新，陈波蓓，管敏鑫. 25个携带线粒体12S rRNA A1555G突变的中国汉族非综合征型耳聋家系[J]. 遗传, 2013, 35(1): 62-72.
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[14]	乔旭，吴芬芳，苏鹏，李庆伟. CDC/MACPF家族成孔毒素研究进展[J]. 遗传, 2010, 32(11): 1126-1132.
[15]	杨爱芬，朱翌，吕建新，杨丽，赵建越，孙冬梅，管敏鑫. 线粒体DNA G7444A突变可能影响A1555G突变的表型表达[J]. 遗传, 2008, 30(6): 728-734.