分枝杆菌噬菌体基因组学研究概况

doi:10.19982/j.issn.1000-6621.20240217

摘要/Abstract

摘要：

分枝杆菌感染给全球带来了很大的健康负担,尤其是耐多药结核病(MDR-TB)对公共卫生和卫生安全的威胁,寻找一种有效对抗分枝杆菌感染的方法成为亟待解决的问题。分枝杆菌噬菌体是特异性感染分枝杆菌的病毒,可以通过裂解宿主菌导致其死亡。目前,大量的分枝杆菌噬菌体已被分离和完成全基因组测序,可以帮助我们深入了解噬菌体的遗传多样性和基因组结构,并推动其应用和发展。因此,本文综述了分枝杆菌噬菌体基因组学的一般特征及基因功能与表达,以提供分枝杆菌噬菌体治疗新思路。

关键词: 分枝杆菌感染, 分枝杆菌噬菌体, 基因组学, 基因表达, 综述文献(主题)

Abstract:

Mycobacterial infections represent a significant global health burden, with multidrug-resistant tuberculosis (MDR-TB) posing a critical public health crisis and a serious threat to health security. Identifying effective strategies to combat mycobacterial infections has become an urgent priority. Mycobacteriophages, viruses that specifically target and lyse mycobacteria, offer a promising approach by effectively killing the host bacteria. litating the advancement of mycobacteriophage applications. This review explores the general genomic characteristics, gene functions, and expression patterns of mycobacteriophages, offering a foundation for further research in this field.

Key words: Mycobacterium infections, Mycobacteriophages, Genomics, Gene expression, Review literature as topic

中图分类号:

刘珂君, 张海鹏, 王鹏. 分枝杆菌噬菌体基因组学研究概况[J]. 中国防痨杂志, 2024, 46(10): 1283-1292. doi: 10.19982/j.issn.1000-6621.20240217

Liu Kejun, Zhang Haipeng, Wang Peng. Overview of genomic research on Mycobacteriophages[J]. Chinese Journal of Antituberculosis, 2024, 46(10): 1283-1292. doi: 10.19982/j.issn.1000-6621.20240217

图/表 3

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参考文献 63

[1]	Honda JR, Virdi R, Chan ED, et al. Global Environmental Nontuberculous Mycobacteria and Their Contemporaneous Man-Made and Natural Niches. Front Microbiol, 2018, 9:2029. doi:10.3389/fmicb.2018.02029. pmid: 30214436
[2]	白慧玲, 王进, 王爱华. 医学免疫学与病原生物学. 郑州: 郑州大学出版社, 2008: 252-262.
[3]	Dedrick RM, Guerrero-Bustamante CA, Garlena RA, et al. Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus. Nat Med, 2019, 25(5): 730-733. doi:10.1038/s41591-019-0437-z.
[4]	Raj CV, Ramakrishnan T. Transduction in Mycobacterium smegmatis. Nature, 1970, 228 (5268): 280-281. doi:10.1038/228280b0.
[5]	Nick JA, Dedrick RM, Gray AL, et al. Host and pathogen response to bacteriophage engineered against Mycobacterium abscessus lung infection. Cell, 2022, 185(11): 1860-1874.e12. doi:10.1016/j.cell.2022.04.024.
[6]	Hatfull GF, Pedulla ML, Jacobs-Sera D, et al. Exploring the mycobacteriophage metaproteome: phage genomics as an educational platform. PLoS Genet, 2006, 2(6): e92. doi:10.1371/journal.pgen.0020092. pmid: 16789831
[7]	Hatfull GF, Cresawn SG, Hendrix RW. Comparative genomics of the mycobacteriophages: insights into bacteriophage evolution. Res Microbiol, 2008, 159(5):332-339. doi:10.1016/j.resmic.2008.04.008. pmid: 18653319
[8]	Hatfull GF. Molecular Genetics of Mycobacteriophages. Microbiol Spectr, 2014, 2(2). doi:10.1128/microbiolspec.MGM2-0032-2013.
[9]	Hatfull GF. Mycobacteriophages. Microbiol Spectr, 2018, 6(5):10.1128/microbiolspec.GPP3-0026-2018. doi:10.1128/microbiolspec.GPP3-0026-2018.
[10]	Hatfull GF, Sarkis GJ. DNA sequence, structure and gene expression of mycobacteriophage L5: a phage system for mycobacterial genetics. Mol Microbiol, 1993, 7 (3): 395-405. doi:10.1111/j.1365-2958.1993.tb01131.x. pmid: 8459766
[11]	刘文, 胡巍, 王洪海. 分枝杆菌噬菌体的分子生物学研究进展及其应用. 微生物学通报, 1999, 26 (1):58-62. doi:10.13344/j.microbiol.china.1999.01.020.
[12]	Ford ME, Sarkis GJ, Belanger AE, et al. Genome structure of mycobacteriophage D29: implications for phage evolution. J Mol Biol, 1998, 279(1): 143-164. doi:10.1006/jmbi.1997.1610. pmid: 9636706
[13]	包孟, 付玉荣, 伊正君. 分枝杆菌噬菌体D29 LysinB的表达及生物信息学分析. 中国病原生物学杂志, 2017, 12(2):106-109. doi:10.13350/j.cjpb.170203.
[14]	Timme TL, Brennan PJ. Induction of bacteriophage from members of the Mycobacterium avium, Mycobacterium intracellulare, Mycobacterium scrofulaceum serocomplex. J General mMicrobiol, 1984, 130 (8): 2059-2066. doi:10.1099/00221287-130-8-2059.
[15]	Jacobs WR Jr, Tuckman M, Bloom BR. Introduction of foreign DNA into mycobacteria using a shuttle phasmid. Nature, 1987, 327 (6122): 532-535. doi:10.1038/327532a0.
[16]	Rybniker J, Kramme S, Small PL. Host range of 14 mycobacteriophages in Mycobacterium ulcerans and seven other mycobacteria including Mycobacterium tuberculosis-application for identification and susceptibility testing. J Med Microbiol, 2006, 55 (Pt 1): 37-42. doi:10.1099/jmm.0.46238-0. pmid: 16388028
[17]	Jacobs WR Jr, Barletta RG, Udani R, et al. Rapid assessment of drug susceptibilities of Mycobacterium tuberculosis by means of luciferase reporter phages. Science, 1993, 260(5109): 819-822. doi:10.1126/science.8484123. pmid: 8484123
[18]	Ford ME, Stenatrom C, Hendrix RW, et al. Mycobacteriophage TM4: genome structure and gene expression. Tuber Lung Dis, 1998, 79 (2): 63-73. doi:10.1054/tuld.1998.0007.
[19]	刘平. 分枝杆菌噬菌体的生物学特性及基因组学研究. 重庆:重庆医科大学, 2012.
[20]	Fan X, Teng T, Xie J, et al. Biology of a novel mycobacterio-phage, SWU1, isolated from Chinese soil as revealed by genomic characteristics. J Virol, 2012, 86(18):10230-10231. doi:10.1128/JVI.01568-12.
[21]	樊祥宇. 分枝杆菌噬菌体的系统生物学研究. 重庆: 西南大学, 2014.
[22]	苏胜兵. 分枝杆菌烈性噬菌体的分离鉴定及其裂解酶基因的克隆与序列分析. 长春: 吉林农业大学, 2012.
[23]	Fan X, Gao X, Xie J, et al. Complete genome sequence analysis of the novel mycobacteriophage Shandong1. Arch Virol, 2017, 162(12):3903-3905. doi:10.1007/s00705-017-3534-7. pmid: 28828700
[24]	Gong Z, Lv X, Xie J, et al. Genomic and proteomic portrait of a novel mycobacteriophage SWU2 isolated from China. Infect Genet Evol, 2021, 87:104665. doi:10.1016/j.meegid.2020.104665.
[25]	Pope WH, Bowman CA, Russell DA, et al. Whole genome comparison of a large collection of mycobacteriophages reveals a continuum of phage genetic diversity. Elife, 2015, 4:e06416. doi:10.7554/eLife.06416.
[26]	Voronina OL, Kunda MS, Aksenova EI, et al. Mosaic structure of Mycobacterium bovis BCG genomes as a representation of phage sequences’ mobility. BMC Genomics, 2016, 17(Suppl 14): 1009. doi:10.1186/s12864-016-3355-1. pmid: 28105923
[27]	Sinha A, Eniyan K, Bajpai U, et al. Characterization and genome analysis of B 1 sub-cluster mycobacteriophage PDRPxv. Virus Res, 2020, 279:197884. doi:10.1016/j.virusres.2020.197884.
[28]	Hatfull GF, Jacobs-Sera D, Lawrence JG, et al. Comparative genomic analysis of 60 Mycobacteriophage genomes: genome clustering, gene acquisition, and gene size. J Mol Biol, 2010, 397 (1): 119-143. doi:10.1016/j.jmb.2010.01.011.
[29]	Hatfull GF. Mycobacteriophages: genes and genomes. Annu Rev Microbiol, 2010, 64:331-356. doi:10.1146/annurev.micro.112408.134233. pmid: 20528690
[30]	Zheng H, Olia AS, Gonen M, et al. A conformational switch in bacteriophage p 22 portal protein primes genome injection. Mol Cell, 2008, 29(3):376-383. doi:10.1016/j.molcel.2007.11.034.
[31]	Hatfull GF. Mycobacteriophages: From Petri dish to patient. PLoS Pathog, 2022, 18(7):e1010602. doi:10.1371/journal.ppat.1010602.
[32]	Garcia M, Pimentel M, Moniz-Pereira J. Expression of Mycobacteriophage Ms6 lysis genes is driven by two sigma(70)-like promoters and is dependent on a transcription termination signal present in the leader RNA. J Bacteriol, 2002, 184(11): 3034-3043. doi:10.1128/JB.184.11.3034-3043.2002. pmid: 12003945
[33]	Pham TT, Jacobs-Sera D, Pedulla ML, et al. Comparative genomic analysis of mycobacteriophage Tweety: evolutionary insights and construction of compatible site-specific integration vectors for mycobacteria. Microbiology (Reading), 2007, 153(Pt 8): 2711-2723. doi:10.1099/mic.0.2007/008904-0.
[34]	Zeynali Kelishomi F, Khanjani S, Fardsanei F, et al. Bacteriophages of Mycobacterium tuberculosis, their diversity, and potential therapeutic uses: a review. BMC Infect Dis, 2022, 22(1):957. doi:10.1186/s12879-022-07944-9. pmid: 36550444
[35]	Catalão MJ, Pimentel M. Mycobacteriophage Lysis Enzymes: Targeting the Mycobacterial Cell Envelope. Viruses, 2018, 10(8):428. doi:10.3390/v10080428.
[36]	Yang H, Yu J, Wei H. Engineered bacteriophage lysins as novel anti-infectives. Front Microbiol, 2014, 5:542. doi:10.3389/fmicb.2014.00542. pmid: 25360133
[37]	宋磊. 分枝杆菌噬菌体L5 LysA、LysB的表达及活性研究. 长春: 吉林农业大学, 2014.
[38]	Kamilla S, Jain V. Mycobacteriophage D29 holin C-terminal region functionally assists in holin aggregation and bacterial cell death. FEBS J, 2016, 283 (1): 173-190. doi:10.1111/febs.13565. pmid: 26471254
[39]	Catalão MJ, Gil F, Moniz-Pereira J, et al. Diversity in bacterial lysis systems: bacteriophages show the way. FEMS Microbiol Rev, 2013, 37(4): 554-571. doi:10.1111/1574-6976.12006.
[40]	Peña CE, Kahlenberg JM, Hatfull GF. Assembly and activation of site-specific recombination complexes. Proc Natl Acad Sci U S A, 2000, 97(14): 7760-7765. doi:10.1073/pnas.140014297.
[41]	申严杰, 胡昌华, 王洪海, 等. 分枝杆菌噬菌体整合及裂解的分子机理. 微生物学报, 2005, 45(5):808-811. doi:10.13343/j.cnki.wsxb.2005.05.034.
[42]	Kusano K, Takahashi NK, Yoshikura H, et al. Involvement of RecE exonuclease and RecT annealing protein in DNA double-strand break repair by homologous recombination. Gene, 1994, 138(1/2):17-25. doi:10.1016/0378-1119(94)90778-1.
[43]	Górecka KM, Krepl M, Szlachcic A, et al. RuvC uses dynamic probing of the Holliday junction to achieve sequence specificity and efficient resolution. Nat Commun, 2019, 10(1):4102. doi:10.1038/s41467-019-11900-8. pmid: 31506434
[44]	Smith MC, Thorpe HM. Diversity in the serine recombinases. Mol Microbiol, 2002, 44(2): 299-307. doi:10.1046/j.1365-2958.2002.02891.x. pmid: 11972771
[45]	Hatfull GF. Actinobacteriophages: Genomics, Dynamics, and Applications. Annu Rev Virol, 2020, 7(1):37-61. doi:10.1146/annurev-virology-122019-070009. pmid: 32991269
[46]	Ojha A, Anand M, Bhatt A, et al. GroEL1: a dedicated chaperone involved in mycolic acid biosynthesis during biofilm formation in mycobacteria. Cell, 2005, 123(5): 861-873. doi:10.1016/j.cell.2005.09.012. pmid: 16325580
[47]	Bhawsinghka N, Dutta A, Mukhopadhyay J, et al. A transcriptomic analysis of the mycobacteriophage D29 genome reveals the presence of novel stoperator-associated promoters in its right arm. Microbiology (Reading), 2018, 164(9): 1168-1179. doi:10.1099/mic.0.000693. pmid: 30024363
[48]	Li X, Long X, Chen L, et al. Mycobacterial phage TM4 requires a eukaryotic-like Ser/Thr protein kinase to silence and escape anti-phage immunity. Cell Host Microbe, 2023, 31(9): 1469-1480.e4. doi:10.1016/j.chom.2023.07.005. pmid: 37567169
[49]	丛聪. 沙门菌裂解性噬菌体的筛选、基因组学分析及其在肉鸡产品抗菌中的应用. 大连: 大连理工大学, 2021. doi:10.26991/d.cnki.gdllu.2021.004986.
[50]	邬亭亭. 分枝杆菌噬菌体鸡尾酒制剂应用于耐药结核病治疗的探索性研究. 重庆: 重庆医科大学, 2012.
[51]	Łobocka M, Dᶏbrowska K, Górski A. Engineered Bacteriophage Therapeutics: Rationale, Challenges and Future. BioDrugs, 2021, 35(3): 255-280. doi:10.1007/s40259-021-00480-z. pmid: 33881767
[52]	樊祥宇, 谢建平. 分枝杆菌噬菌体重组系统及其应用. 中国生物工程杂志, 2012, 32(9):101-106. doi:10.13523/j.cb.20120916.
[53]	Jacobs WR Jr, Snapper SB, Lugosi L, et al. Development of BCG as a recombinant vaccine vehicle. Curr Top Microbiol Immunol, 1990, 155: 153-160. doi:10.1007/978-3-642-74983-4_11. pmid: 2407431
[54]	Freeman KG, Wetzel KS, Zhang Y, et al. A Mycobacteriophage-Based Vaccine Platform: SARS-CoV-2 Antigen Expression and Display. Microorganisms, 2021, 9(12): 2414. doi:10.3390/microorganisms9122414.
[55]	Mitsunaka S, Yamazaki K, Pramono AK, et al. Synthetic engineering and biological containment of bacteriophages. Proc Natl Acad Sci U S A, 2022, 119(48): e2206739119. doi:10.1073/pnas.2206739119.
[56]	Manoutcharian K. Bacteriophages as tools for vaccine and drug development. Expert Rev Vaccines, 2005, 4(1): 5-7. doi:10.1586/14760584.4.1.5. pmid: 15757465
[57]	Harada LK, Silva EC, Campos WF, et al. Biotechnological applications of bacteriophages: State of the art. Microbiol Res, 2018, 212-213: 38-58. doi:10.1016/j.micres.2018.04.007.
[58]	Sass P, Bierbaum G. Lytic activity of recombinant bacteriophage phi11 and phi12 endolysins on whole cells and biofilms of Staphylococcus aureus. Appl Environ Microbiol, 2007, 73(1):347-352. doi:10.1128/AEM.01616-06.
[59]	Son JS, Lee SJ, Jun SY, et al. Antibacterial and biofilm removal activity of a podoviridae Staphylococcus aureus bacteriophage SAP-2 and a derived recombinant cell-wall-degrading enzyme. Appl Microbiol Biotechnol, 2010, 86(5): 1439-1449. doi:10.1007/s00253-009-2386-9.
[60]	Domenech M, García E, Moscoso M. In vitro destruction of Streptococcus pneumoniae biofilms with bacterial and phage peptidoglycan hydrolases. Antimicrob Agents Chemother, 2011, 55(9):4144-4148. doi:10.1128/AAC.00492-11. pmid: 21746941
[61]	Briers Y, Walmagh M, Van Puyenbroeck V, et al. Engineered endolysin-based “Artilysins” to combat multidrug-resistant gram-negative pathogens. mBio, 2014, 5(4): e01379-14. doi:10.1128/mBio.01379-14.
[62]	Chakraborty P, Bajeli S, Kaushal D, et al. Biofilm formation in the lung contributes to virulence and drug tolerance of Mycobacterium tuberculosis. Nat Commun, 2021, 12(1):1606. doi:10.1038/s41467-021-21748-6. pmid: 33707445
[63]	Ackart DF, Lindsey EA, Podell BK, et al. Reversal of Mycobacterium tuberculosis phenotypic drug resistance by 2-aminoimi-dazole-based small molecules. Pathog Dis, 2014, 70 (3): 370-378. doi:10.1111/2049-632X.12143. pmid: 24478046

簇	亚簇	成员数量	平均长度 (bp)	平均GC %含量	平均基因数量	平均tRNA 基因数量	簇	成员数量	平均长度 (bp)	平均GC %含量	平均基因数量	平均tRNA 基因数量
A	19	770	51603	63.3	90.5	1.2	R	10	71339	56.0	98	0
B	13	415	68822	67.1	98.3	0	S	19	64972	63.4	107	0
C	2	188	155628	64.7	230.5	32.9	T	7	42746	66.2	61	-
D	2	22	64789	59.6	88.8	0	U	3	66864	50.4	104	1
E	0	130	75493	63.0	142.6	1.9	V	5	77907	56.9	145.3	23.3
F	5	237	57338	61.5	104.1	0	W	6	61013	67.5	-	-
G	5	70	42363	66.9	62	0	X	2	88037	56.7	-	-
H	2	12	69127	57.3	98.7	0	Y	4	76836	66.7	-	-
I	2	7	50320	66.4	80.2	0	Z	2	50807	66.0	-	-
J	0	43	111094	60.9	235.3	1.6	AA	2	140785	67.4	-	-
K	8	185	59991	66.8	93.6	0.9	AB	5	49672	58.6	71	0
L	5	76	74381	58.9	124.7	10.3	AC	4	70029	49.8	-	-
M	3	20	81622	61.3	141.3	18.7	AD	4	64670	66.1	93	0
N	0	43	42941	66.2	68.9	0	AE	3	71540	58.8	-	-
O	0	28	71124	65.4	121.1	0	AF	2	62538	65.2	-	-
P	6	49	47839	67.0	79.3	0	AG	2	55047	66.0	-	-
Q	0	22	53835	67.4	81	0	AH	2	54800	70.4	-	-

噬菌体名称	宿主菌	菌种	簇	基因长度(bp)	GC%含量	发现年份	发现地
StAugustine	耻垢分枝杆菌	mc²155	单胞体	101031	65.7	2023	佐治亚州,美国
P3MA	脓肿分枝杆菌	330	单胞体	41234	63.4	2023	未知
MooMoo	耻垢分枝杆菌	mc²155	单胞体	55178	62.0	2011	肯塔基州,美国
LilSpotty	耻垢分枝杆菌	mc²155	单胞体	49798	64.7	2018	加尼福利亚州,美国
Kumao	耻垢分枝杆菌	mc²155	单胞体	70373	62.1	2015	宾夕法尼亚州,美国
IdentityCrisis	耻垢分枝杆菌	mc²155	单胞体	38341	65.0	2018	佛罗里达州,美国
DS6A	结核分枝杆菌	H37Rv	单胞体	60588	68.4	1960	未知
平均	-	-	-	59506	64.5	-	-