张韬，扬州大学教授，江苏特聘教授，博士生导师，国家级青年人才计划入选者，江苏省“双创计划”双创团队领军人才，2004年本科毕业于四川大学，2013年博士毕业于电子科技大学，2010年至2016年于美国威斯康辛大学-麦迪逊分校园艺系从事学习、研究工作， 2016年9月加入扬州大学从事科研和教学工作。主要从事植物基因组信息的挖掘及解析, 基因组编辑系统优化等工作，先后承担国家转基因重大专项等课题；在Genome Biology, PNAS, Plant Cell, Nucleic Acids Research等期刊发表SCI论文50余篇。

调控元件的高通量挖掘

    真核生物的基因表达与调控是一系列顺式调控元件（cis-regulatory elements，CRMs）与调控蛋白（regulatory proteins）互作的结果。顺式调控元件（如，启动子、增强子等）本身不编码蛋白，需与调控蛋白（如转录因子）结合才能发挥其生物学作用。根据进一步的研究发现，顺式调控元件往往与染色质的结构密切相关，开放染色质为调控元件富集的区域。我们通过ATAC-seq等文库，使用生物信息学大数据分析方法确定了植物基因组中的开放染色质；鉴定开放染色质位点上的顺式调控元件富集区域；结合多组学数据预测对作物全基因组启动子和增强子进行通量预测，并用实验方法进行验证。

基因组编辑体系的优化

    CRISPR-Cas9、CRISPR-Cas12a （Cpf1）等核酸酶可针对特定基因组DNA序列实现可编程定向剪切，并能以前所未有的精准度和便捷度进行基因组编辑，被广泛应用于动、植物及微生物的基因功能解析、新种质创制、基因治疗等基础研究及实践应用中，被认为是21世纪生物技术领域的重大突破。针对植物基因组编辑基础研究及应用实践中如何有效进行CRISPR-Cas核酸酶脱靶效应评价的科学问题，在充分借鉴前期相关工作实验设计、实施策略、研究结果的基础上，以水稻为模型，基于“全基因组测序+大数据”分析策略，对CRISPR-Cas9、CRISPR-Cpf1 （Cas12a）介导的植物基因组编辑脱靶效应进行有效解读，得出Cas9、Cpf1核酸酶的表达没有诱导水稻基因组产生新的变异，同时提出提升gRNA的设计严谨性可以消除基因组编辑事件中脱靶效应的潜在影响，为进一步推动CRISPR-Cas基因组编辑技术发展、打消公众对基因组编辑植物的疑虑及相关产业政策的制定提供了确实科学证据及重要参考依据，同时基因编辑工具的发展为调控元件挖掘鉴定提供了有力的支持。

实验室网站： http://bioinfor.yzu.edu.cn/

发表论文:

2023

• Han YS†, Liu GQ†, Wu YC, Bao Y, Zhang Y*, Zhang T*.CrisprStitch: Fast evaluation of the efficiency of CRISPR editing systems. Plant Communications DOI: https://doi.org/10.1016/j.xplc.2023.100783 

• Wang ZY, Lei YJ, Liu GQ, Ning Y, Ning YR, Zhang T*, Xi M*. Male-Specific Sequence in Populus simonii Provides Insights into Gender Determination of Poplar. Forests 2023, 14:2385

• Gurel F†, Wu YC†, Pan CT, Cheng YH,Li G ,Zhang T*, Qi YP*. On- and Off-Target Analyses of CRISPR-Cas12b Genome Editing Systems in Rice. The CRISPR Journal 2023, 6:62-74

• Zhong ZH†, Liu GQ†, Tang ZJ†, Xiang SH†, Yang L, Huang L, He Y, He Y, Fan TT, Liu SS, Zheng XL, Zhang T, Qi YP*, Huang J*, Zhang Y*. Efficient plant genome engineering using a probiotic sourced CRISPR-Cas9 system. Nature Communications 2023, 14:6102

• Zhang YX†, Wu YC†, Li G†, Qi A, Zhang Y, Zhang T*, Qi Y*. Genome-wide investigation of multiplexed CRISPR-Cas12a-mediated editing in rice. Plant Genome 2023, 16:e20266

• Sretenovic S†, Green Y†, Wu YC†, Cheng YH†, Zhang T*, Eck J.V*, Qi YP*.Genome- and transcriptome-wide off-target analyses of a high-efficiency adenine base editor in tomato. Plant Physiology 2023, 193:291–303

• Chen C†, Han YS†, Xiao H, Zou BC, Wu DD, Sha LN, Yang CR, Liu SQ, Cheng YR, Wang Y, Kang HY, Fan X, Zhou YH, Zhang T* , Zhang HQ*. Chromosome-specific painting in Thinopyrum species using bulked oligonucleotides. Theoretical and Applied Genetics 2023, 136:177

• Bao Y†, Wei YY†, Liu YL†, Gao JJ, Cheng S, Liu GQ, You Q, Liu P, Lu QW, Li PT, Zhang SL, Hu N, Han YS, Liu S, Wu YC, Yang QQ, Li ZG, Ao GW, Liu F, Wang KB, Jiang JM, Zhang T*, Zhang WL* ,Peng RH*. Genome-wide chromatin accessibility landscape and dynamics of transcription factor networks during ovule and fiber development in cotton. BMC Biology 2023, 21:165

• Zhou JP†, Liu GQ†, Zhao YX, Zhang R, Tang X, Li L, Jia XY, Guo YC, Han YS, Bao Y, He Y, Han QQ, Yang H, Zheng XL, Qi YP*, Zhang T*, Zhang Y*. An efficient CRISPR–Cas12a promoter editing system for crop improvement. Nature Plants 2023, 9:588-604

2022

• Liu S†, Bao Y†, Deng H†, Liu GQ, Han YS, Wu YC, Zhang T*, Chen C*. The Methylation Inhibitor 5-Aza-2′-Deoxycytidine Induces Genome-Wide Hypomethylation in Rice Rice 2022, 15:35

• Xue C†, Liu GQ†, Sun S, Liu XY, Guo R, Cheng ZK, Yu HX, Gu MH, Liu K, Zhou Y*, Zhang T*, Gong ZY*. De Novo Centromere Formation in Pericentromeric Region of Rice Chromosome 8. The Plant Journal 2022, 111(3):859-871

• Wu YC†, Ren QR†, Zhong ZH†, Liu GQ†, Han YS, Bao Y, Liu L, Xiang SY, Liu S, Tang X, Zhou JP, Zheng XL, Sretenovic S, Zhang T*, Qi YP*, Zhang Y*. Genome-wide analyses of PAM-relaxed Cas9 genome editors reveal substantial off-target effects by ABE8e in rice. Plant Biotechnology Journal 2022, 20(9): 1670-1682

• Tao ST†, Liu P†, Shi YN, Feng YL, Gao JJ, Chen LF, Zhang AC, Cheng XJ, Wei HR, Zhang T*, Zhang WL*. Single-Cell Transcriptome and Network Analyses Unveil Key Transcription Factors Regulating Mesophyll Cell Development in Maize. Genes 2022, 13(2):374

• Feng YL, Tao ST, Zhang PY, Sperti FR, Liu GQ, Cheng XJ, Zhang T, Yu HX, Wang XE, Cheng CY, Monchaud D, Zhang WL*. Epigenomic features of DNA G-quadruplexes and their roles in regulating rice gene transcription. Plant Physiology 2022, 188(3): 1632–1648

• Wu YC†, He Y†, Sretenovic S, Liu SS, Cheng YH, Han YS, Liu GQ, Bao Y, Fang Q, Zheng XL, Zhou JP, Qi YP*, Zhang Y*, Zhang T*. CRISPR-BETS: A base editing design tool for generating stop codons. Plant Biotechnology Journal 2022, 20(3):499-510

2021

• Ding Y, Zhu JN, Zhao DS, Liu QQ, Yang QQ*, ZhangT*. Targeting Cis-Regulatory Elements for Rice Grain Quality Improvement. Frontiers in Plant Science 2021, 12:705834

• Liu GQ, Zhang T*. Single Copy Oligonucleotide Fluorescence In Situ Hybridization Probe Design Platforms: Development, Application and Evaluation. International Journal of Molecular Sciences 2021, 22(13):7124

• Randall L.B†, Sretenovic S†, Wu YC†, Yin D, Zhang T, Eck J.V, Qi YP*. Genome- and transcriptome-wide off-target analyses of an improved cytosine base editor. Plant Physiology 2021, 187(1):73-87

• Ren QR†, Sretenovic S†, Liu GQ†, Zhong ZH, Wang JH, Huang L, Tang X, Guo YC, Liu L, Wu YC, Zhou J, Zhao YX, Yang H, He Y, Liu SS, Yin DS, Mayorga R, Zheng XL, Zhang T*, Qi YP*, Zhang Y*. Improved plant cytosine base editors with high editing activity, purity, and specificity. Plant Biotechnology Journal 2021, 19(10):2052-2068

• Zhang T†*, Liu GQ†, Zhao HN, Braz G.T, Jiang JM*. Chorus2: design of genome‐scale oligonucleotide‐based probes for fluorescence in situ hybridization. Plant Biotechnology Journal 2021, 19(10):1967-1978

• Meng FL†, Zhao HN†, Zhu B, Zhang T, Yang, Li Y, Han YP, Jiang JM*. Genomic Editing of Intronic Enhancers Unveils Their Role in Fine-Tuning Tissue-Specific Gene Expression in Arabidopsis thaliana. The Plant Cell 2021, 33(6):1997-2014

• Zhang C, Zhang JX, Tang YJ, Liu KW, Liu Y, Tang JQ, Zhang T, Yu HX*. DEEP GREEN PANICLE1 suppresses GOLDEN2-LIKE activity to reduce chlorophyll synthesis in rice glumes. Plant Physiology 2021, 185(2):469-477

• Liu GQ, Qi YP, Zhang T. Analysis of Off-Target Mutations in CRISPR-Edited Rice Plants Using Whole-Genome Sequencing. Methods in Molecular Biology 2021, 2238:145-172

• Li GR†, Zhang T†, Yu ZH, Wang HJ, Yang EN, Yang ZJ*. An efficient Oligo‐FISH painting system for revealing chromosome rearrangements and polyploidization in Triticeae. The Plant Journal 2021, 105(4):978-993

2020

• Liu YL, Wang XY, Wei YY, Liu Z, Lu QW, Liu F, Zhang T*, Peng RH*. Chromosome Painting Based on Bulked Oligonucleotides in Cotton. Frontiers in Plant Science 2020, 11:802

• Zhao HN†, Zhang WL†*, Zhang T†, Lin Y, Hu YD, Fang C, Jiang JM*. Genome-wide MNase hypersensitivity assay unveils distinct classes of open chromatin associated with H3K27me3 and DNA methylation in Arabidopsis thaliana. Genome Biology 2020, 21:24

• Song XY, Song RR, Zhou JW, Yan WK, Zhang T, Sun HJ, Xiao J, Wu YF, Xi ML, Lou QF, Wang HY*, Wang XE*. Development and application of oligonucleotide-based chromosome painting for chromosome 4D of Triticum aestivum L. Chromosome Research 2020, 8(2):177-182

• Braz G.T, Martins L. do, Zhang T, Albert P.S, Birchler J.A, Jiang JM* A universal chromosome identification system for maize and wild Zea species. Chromosome Research 2020, 28(2):183-194

• Liu GQ, Zhang Y*, Zhang T*. Computational approaches for effective CRISPR guide RNA design and evaluation. Computational and Structural Biotechnology Journal 2020, 18:35-44

• Liu XY†, Sun S†, Wu Y, Zhou Y, Gu SW, Yu HX, Yi CD, Gu MH, Jiang JM, Liu B, Zhang T*, Gong ZY*. Dual‐color oligo‐FISH can reveal chromosomal variations and evolution in Oryza species. The Plant Journal 2020, 101:112-121

• Xin HY†, Zhang T†, Wu YF, Zhang WL, Zhang PD, Xi ML*, Jiang JM. An extraordinarily stable karyotype of the woody Populus species revealed by chromosome painting. The Plant Journal 2020, 101:253-264

• Cover: The Plant Journal Volume 101, Issue 2

2019

• Liu S†, Liu GQ†, Cheng PF, Xue C, Zhou Y, Chen X, Ye L, Qiao ZY*, Zhang T*, Gong Z.Y* Genome-wide Profiling of Histone Lysine Butyrylation Reveals its Role in the Positive Regulation of Gene Transcription in Rice. Rice 2019, 12:86

• Alvarez J.M, Moyano T.C, Zhang T, Gras D.E, Herrea F.J, Araus V. O’Brien J.A, Carrillo L, Medina J, Vicente-Carbajosa J, Jiang JM, Gutierrez R.A* Local changes in chromatin accessibility and transcriptional networks underlying the nitrate response in Arabidopsis roots. Molecular Plant 2019, 12(12):1545-1560

• Ren QR, Zhong ZH, Wang Y, You Q, Li Q, Yuan MZ, He Y, Qi CY, Tang X, Zheng XL, Zhang T*, Qi YP*, Zhang Y*. Bidirectional promoter based CRISPR-Cas9 systems for plant genome editing Frontiers in Plant Science 2019, 10:1173

• Zhong ZH†, Sretenovic S†, Ren QR†, Yang LJ, Bao Y, Qi CY, Yuan MZ, He Y, Liu SS, Wang JH, Huang L, Wang Y, Baby DB, Wang D, Zhang T, Qi YP*, Zhang Y*. Improving plant genome editing with high-fidelity xCas9 and non-canonical PAM-targeting Cas9-NG. Molecular Plant 2019, 12(7):1027-1036

• Albert P.S†, Zhang T†, Semrau K, Rouillard JM, Kao YH, Wang CJ, Danilova T.V, Jiang JM, and Birchler J*. Whole-chromosome paints in maize reveal rearrangements, nuclear domains, and chromosomal relationships. Proceedings of the National Academy of Sciences of the United States of America 2019, 16(5):1679-1685

• Malzahn AA†, Tang X†, Lee K, Ren QR, Sretenovic S, Zhang YX, Chen HQ, Kang MJ, Bao Y, Zheng XL, Deng KJ, Zhang T, Salcedo V, Wang K, Zhang Y*, Qi YP*. Application of CRISPR-Cas12a temperature sensitivity for improved genome editing in rice, maize, and Arabidopsis. BMC Biology 2019, 17(1):9

• Tang X†, Ren QR†, Yang LJ, Bao Y, Zhong ZH, He Y, Liu SS, Qi CY, Liu BL, Wang Y, Sretenovic S, Zhang YX, Zheng XL, Zhang T*, Qi YP*, Zhang Y*. Single transcript unit CRISPR 2.0 systems for robust Cas9 and Cas12a mediated plant genome editing. Plant Biotechnology Journal 2019, 17(7):1431-1445

2018

• Wu ZG†, Fang DM†, Yang R†, Gao F, An XY, Zhou XX, Li YF, Yi CD, Zhang T, Liang CZ, Cui P*, Cheng ZK*, Luo Q*. De novo genome assembly of Oryza granulata reveals rapid genome expansion and adaptive evolution. Communications Biology 2018, 1:84

• Tang X†, Liu GQ†, Zhou JP†, Ren QR, You Q, Tian L, Xin XH, Zhong ZH, Liu BL, Zheng XL, Zhang DW, Malzahn A, Gong ZY, Qi YP*, Zhang, T*, and Zhang Y*. (2018). A large-scale whole-genome sequencing analysis reveals highly specific genome editing by both Cas9 and Cpf1(Cas12a) nucleases in rice. Genome Biology 2018, 19:84

• You Q, Zhong ZH, Ren QR, Hassan F, Zhang Y*, Zhang T*. CRISPRMatch: An Automatic Calculation And Visualization Tool For High-throughput CRISPR Genome-editing Data Analysis. International Journal of Biological Sciences 2018, 14(8):858-862.

• Yang XM†, Zhao HN†, Zhang T, Zeng ZX, Zhang PD, Zhu B, Han YH, Braz GT, Casler MD, Schmutz J, and Jiang JM*. Amplification and adaptation of centromeric repeats in polyploid switchgrass species. New Phytologist 2018, 218:1645-1657

• Hou LL†, Xu M†, Zhang T†, Xu ZH, Wang WY, Zhang JX, Yu MM, Ji W, Zhu CW, Gong ZY, Gu MH, Jiang JM and Yu HX*. Chromosome painting and its applications in cultivated and wild rice. BMC Plant Biology 2018, 18:110.

• Dong ZB†, Yu J†, Li H, Huang W, Xu L, Zhao Y, Zhang T, Xu W, Jiang JM, Su Z*, and Jin WW*. Transcriptional and epigenetic adaptation of maize chromosomes in Oat-Maize addition lines. Nucleic Acids Research 2018, 46(10):5012-5028.

• Zhong ZH†, Zhang YX†, You Q†, Tang X, Ren QR, Liu SS, Yang LJ, Wang Y, Liu XP, Liu BL, Zhang T, Zheng XL, Le Y, Zhang Y*, and Qi YP*. Plant genome editing using FnCpf1 and LbCpf1 nucleases at redefined and altered PAM sites. Molecular Plant 2018, 11:999-1002.

• Xin H†, Zhang T†, Han YH, Wu YF, Shi JS, Xi ML*, and Jiang JM. Chromosome painting and comparative physical mapping of the sex chromosomes in Populus tomentosa and Populus deltoides. Chromosoma 2018, 127(3):313-321.

• Braz GT†, He L†, Zhao HN†, Zhang T†, Semrau K, Rouillard JM, Torres GA, Jiang JM*. Comparative oligo-FISH mapping: an efficient and powerful methodology to reveal karyotypic and chromosomal evolution. Genetics 2018, 208(2):513-523.

2017

• Zhang R, Xue C, Liu GQ, Liu XY, Zhang ML, Wang X, Zhang T*, and Gong ZY*. Segmental Duplication of Chromosome 11 and its Implications for Cell Division and Genome-wide Expression in Rice. Scientific Reports 2017, 1(7):2689.

• Tang X†, Lowder LG†, Zhang T, Maizahn AA, Zheng XL, Voytas DF, Zhong ZH, Chen YY, Ren QR, Li Q, Kirkland ER, Zhang Y*, and Qi YP*. A CRISPR-Cpf1 system for efficient genome editing and transcriptional repression in plants. Nature Plants 2017, 3:17018.

• Marand AP, Zhang T, Zhu B, and Jiang JM*. Towards genome-wide prediction and characterization of enhancers in plants. Biochimica et Biophysica Acta-Gene Regulatory Mechanisms 2017, 1860(1):131-139.

• Zhou JP†, Deng KJ†, Cheng Y, Zhong ZH, Tian L, Tang X, Tang AT, Zheng XL, Zhang T, Qi YP*, and Zhang Y*. CRISPR-Cas9 Based Genome Editing Reveals New Insights into MicroRNA Function and Regulation in Rice. Frontiers in Plant Science 2017, 8:1598.

2016

• Zhang T, Marand A, Jiang JM*. PlantDHS: A Database for DNase I Hypertensive Sites in Plants. Nucleic Acids Research 2016, 44(D1):D1148-D1153.

2015

• Zhang T†, Zhang WL†, and Jiang JM*. Genome-wide nucleosome occupancy and positioning and their impact on gene expression and evolution in plants. Plant Physiology 2015, 168(4):1406-1416.

• Han YH†, Zhang T†, Thammapichai P, Weng YQ, and Jiang JM*. Chromosome-specific painting in Cucumis species using bulked oligonucleotides. Genetics 2015, 200(3):771-779.

• Zhu B†, Zhang WL†, Zhang T†, Liu B, Jiang JM*. Genome-wide prediction and validation of intergenic enhancers in Arabidopsis using open chromatin signature. The Plant Cell 2015, 27(9):2415-2426.

2014

• Zhang T, Li GR, Yang ZJ, Nevo E. Adaptive evolution of duplicated hsp17 genes in wild barley from microclimatically divergent sites of Israel. Genetics and Molecular Research 2014, 13(1):1220-1232.

• Zhang WL, Zhang T, Wu YF, Jiang JM. Open Chromatin in Plant Genomes. Cytogenetic and Genome Research 2014(1-3), 143:18-27.

• Yang LM†, Koo, DH†, Li D, Zhang T, Jiang JM, Luan FS, Renner SS, Henaff E, Sanseverino W, Garcia-Mas J, Casacuberta J, Senalik DA, Simon PW, Chen JF, and Weng YQ. Next-generation sequencing, FISH mapping and synteny-based modeling reveal mechanisms of decreasing dysploidy in Cucumis. The Plant Journal 2014, 77(1):16-30.

2013

• Zhang T†, Talbert PB†, Zhang WL†, Wu YF, Yang ZJ, Henikoff JG, Henikoff S, Jiang JM. The CentO satellite confers translational and rotational phasing on cenH3 nucleosomes in rice centromeres. Proceedings of the National Academy of Sciences of the United States of America 2013, 110(50):E4875–E4883.

• Commentary: Heslop-Harrison, J.S. and Schwarzacher, T. Nucleosomes and centromeric DNA packaging. Proceedings of the National Academy of Sciences of the United States of America 2013, 110(50):19974-19975.

• Iovene M, Zhang T, Lou Q, Buell CR, Jiang JM. Copy number variation in potato - an asexually propagated autotetraploid species. The Plant Journal 2013, 75(1):80-89.

• Wei W, Zhang T, Lin D, Yang ZJ, Guo FB. Transcriptional abundance is not the single force driving the evolution of bacterial proteins. BMC Evolutionary Biology 2013, 13(1):162.

• Yang ZJ, Zhang T, Lang T, Li G, Chen G, Nevo E. Transcriptome Comparative Profiling of Barley eibi1 Mutant Reveals Pleiotropic Effects of HvABCG31 Gene on Cuticle Biogenesis and Stress Responsive Pathways. International Journal of Molecular Sciences 2013, 14(10):20478-20491.

• Dong ZB, Jiang C, Chen X, Zhang T, Ding L, Song W, Luo H, Lai J, Chen H, Liu R, Jin WW. Maize LAZY1 Mediates Shoot Gravitropism and Inflorescence Development through Regulating Auxin Transport, Auxin Signaling, and Light Response. Plant Physiology 2013, 163(3):1306-1322.

2012

• Zhang WL†, Zhang T†, Wu YF†, Jiang JM. Genome-Wide Identification of Regulatory DNA Elements and Protein-Binding Footprints Using Signatures of Open Chromatin in Arabidopsis. The Plant Cell 2012, 24(7):2719-2731.

2011

• Yang ZJ, Zhang T, Li GR, Nevo E. Adaptive microclimatic evolution of the dehydrin 6 gene in wild barley at “Evolution Canyon”, Israel. Genetica 2011, 139(11-12):1429-1438.

• Wang XH, Zhang T, Wen ZN, Xiao H, Yang ZJ, Chen GX, Zhao X. The chromosome number, karyotype and genome size of the desert plant diploid Reaumuria soongorica (Pall.) Maxim. Plant Cell Reports 2011, 30(6):955-964.

• Tang ZX, Fu SL, Ren ZL, Zhang T, Zou YT, Yang ZJ, Li GR, Zhou JP, Zhang HQ, Yan BJ, Zhang HY, Tan FQ. Diversity and evolution of four dispersed repetitive DNA sequences in the genus Secale. Genome 2011, 54(4):285-300.

2010

• Li GR, Zhang T, Wei P, Jia J, Yang ZJ. Sequence analysis of alpha-gliadin genes from Aegilops tauschii native to China. Asian Journal of Agricultural Sciences 2010, 2(4):128-135.

• Li GR, Zhang T, Ban Y, Yang ZJ. Molecular characterization and evolutionary analysis of alpha-gliadin genes from Eremopyrum bonaepartis (Triticeae). Journal of Agricultural Science (Toronto) 2010, 2(4):30-36.

2009

• Yang ZJ, Zhang T, Bolshoy A, Beharav A, Nevo E. Adaptive microclimatic structural and expressional dehydrin 1 evolution in wild barley, Hordeum spontaneum, at ‘Evolution Canyon’, Mount Carmel, Israel. Molecular Ecology 2009, 18(9):2063-2075.

• Yang ZJ, Li GR, Jia JQ, Zeng X, Lei MP, Zeng ZX, Zhang T, Ren ZL. Molecular cytogenetic characterization of wheat–Secale africanum amphiploids and derived introgression lines with stripe rust resistance. Euphytica 2009, 167(2):197-202.

• Li GR, Liu C, Zeng ZX, Jia J-Q, Zhang T, Zhou JP, Ren ZL, Yang ZJ. Identification of α-gliadin genes in Dasypyrum in relation to evolution and breeding. Euphytica 2009, 165(1):155-163.

2006

• Hu GK, Feng H, Zhang T, Yan Y, Wu B, Jiang Q, Wu JM, Zhang YZ. Molecular cloning of cDNAs for 14-3-3 and its protein interactions in a white-rot fungus Phanerochaete chrysosporium. Annals of Microbiology 2006, 56(3):191-196.