7-Deazaguanine modifications protect phage DNA from host restriction systems

被引:62
|
作者
Hutinet, Geoffrey [1 ]
Kot, Witold [2 ]
Cui, Liang [3 ]
Hillebrand, Roman [4 ,5 ,15 ]
Balamkundu, Seetharamsingh [3 ]
Gnanakalai, Shanmugavel [3 ]
Neelakandan, Ramesh [3 ]
Carstens, Alexander B. [2 ]
Lui, Chuan Fa [6 ]
Tremblay, Denise [7 ,8 ,9 ]
Jacobs-Sera, Deborah [10 ,11 ]
Sassanfar, Mandana [12 ]
Lee, Yan-Jiun [13 ]
Weigele, Peter [13 ]
Moineau, Sylvain [7 ,8 ,9 ]
Hatfull, Graham F. [10 ,11 ]
Dedon, Peter C. [3 ,4 ,5 ]
Hansen, Lars H. [2 ]
de Crecy-Lagard, Valerie [1 ,14 ]
机构
[1] Univ Florida, Dept Microbiol & Cell Sci, Gainesville, FL 32611 USA
[2] Aarhus Univ, Dept Environm Sci, Roskilde, Denmark
[3] Singapore MIT Alliance Res & Technol, Antimicrobial Resistance Interdisciplinary Res Gr, Campus Res Excellence & Technol Enterprise, Singapore 138602, Singapore
[4] MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA
[5] MIT, Ctr Environm Hlth Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA
[6] Nanyang Technol Univ, Sch Biol Sci, 60 Nanyang Dr, Singapore 637551, Singapore
[7] Univ Laval, Fac Sci & Genie, Dept Biochim Microbiol & Bioinformat, Quebec City, PQ G1V 0A6, Canada
[8] Univ Laval, Fac Med Dentaire, Felix Herelle Reference Ctr Bacterial Viruses, Quebec City, PQ G1V 0A6, Canada
[9] Univ Laval, Fac Med Dentaire, Grp Rech Ecol Buccale, Quebec City, PQ G1V 0A6, Canada
[10] Univ Pittsburgh, Pittsburgh Bacteriophage Inst, Pittsburgh, PA 15260 USA
[11] Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA
[12] MIT, Dept Biol, Cambridge, MA 02139 USA
[13] New England Biolabs Inc, Res Dept, Ipswich, MA 01938 USA
[14] Univ Florida, Genet Inst, Gainesville, FL 32610 USA
[15] Nitto Denko Avecia, 125 Fortune Blvd, Milford, MA 01757 USA
基金
美国国家卫生研究院;
关键词
DISCOVERY; BIOSYNTHESIS; MECHANISM; DATABASE; IDENTIFICATION; CYCLOHYDROLASE; GENERATION; SHARE; LIFE; WEB;
D O I
10.1038/s41467-019-13384-y
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Genome modifications are central components of the continuous arms race between viruses and their hosts. The archaeosine base (G(+)), which was thought to be found only in archaeal tRNAs, was recently detected in genomic DNA of Enterobacteria phage 9g and was proposed to protect phage DNA from a wide variety of restriction enzymes. In this study, we identify three additional 2'-deoxy-7-deazaguanine modifications, which are all intermediates of the same pathway, in viruses: 2'-deoxy-7-amido-7-deazaguanine (dADG), 2'-deoxy-7-cyano-7-deazaguanine (dPreQ(0)) and 2'-deoxy-7- aminomethyl-7-deazaguanine (dPreQ(1)). We identify 180 phages or archaeal viruses that encode at least one of the enzymes of this pathway with an overrepresentation (60%) of viruses potentially infecting pathogenic microbial hosts. Genetic studies with the Escherichia phage CAjan show that DpdA is essential to insert the 7-deazaguanine base in phage genomic DNA and that 2'-deoxy-7-deazaguanine modifications protect phage DNA from host restriction enzymes.
引用
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页数:12
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