Escherichia coli induces DNA double-strand breaks in eukaryotic cells

被引:847
作者
Nougayrede, Jean-Philippe
Homburg, Stefan
Taieb, Frederic
Boury, Michele
Brzuszkiewicz, Elzbieta
Gottschalk, Gerhard
Buchrieser, Carmen
Hacker, Joerg
Dobrindt, Ulrich
Oswald, Eric [1 ]
机构
[1] Ecole Natl Vet Toulouse, INRA, UMR 1225, F-31076 Toulouse, France
[2] Univ Wurzburg, Inst Mol Infekt Biol, D-97070 Wurzburg, Germany
[3] Univ Gottingen, Gottingen Genom Lab, D-37077 Gottingen, Germany
[4] Inst Pasteur, Unite Genom Microorganismes Pathogenes, F-75724 Paris, France
[5] CNRS, URA 2171, F-75724 Paris, France
关键词
D O I
10.1126/science.1127059
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
Transient infection of eukaryotic cells with commensal and extraintestinal pathogenic Escherichia coli of phylogenetic group B2 blocks mitosis and induces megalocytosis. This trait is linked to a widely spread genomic island that encodes giant modular nonribosomal peptide and polyketide synthases. Contact with E. coli expressing this gene cluster causes DNA double-strand breaks and activation of the DNA damage checkpoint pathway, leading to cell cycle arrest and eventually to cell death. Discovery of hybrid peptide-polyketide genotoxins in E. coli will change our view on pathogenesis and commensalism and open new biotechnological applications.
引用
收藏
页码:848 / 851
页数:4
相关论文
共 28 条
[1]   DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation [J].
Bakkenist, CJ ;
Kastan, MB .
NATURE, 2003, 421 (6922) :499-506
[2]   The multidrug efflux protein NorM is a prototype of a new family of transporters [J].
Brown, MH ;
Paulsen, IT ;
Skurray, RA .
MOLECULAR MICROBIOLOGY, 1999, 31 (01) :394-395
[3]   Bleomycins: Towards better therapeutics [J].
Chen, JY ;
Stubbe, J .
NATURE REVIEWS CANCER, 2005, 5 (02) :102-112
[4]   Hybrid peptide-polyketide natural products:: Biosynthesis and prospects toward engineering novel molecules [J].
Du, LH ;
Sánchez, C ;
Shen, B .
METABOLIC ENGINEERING, 2001, 3 (01) :78-95
[5]   Exploitation of mammalian host cell functions by bacterial pathogens [J].
Finlay, BB ;
Cossart, P .
SCIENCE, 1997, 276 (5313) :718-725
[6]   Analysis of the genome structure of the nonpathogenic probiotic Escherichia coli strain Nissle 1917 [J].
Grozdanov, L ;
Raasch, C ;
Schulze, E ;
Sonnenborn, U ;
Gottschalk, G ;
Hacker, J ;
Dobrindt, U .
JOURNAL OF BACTERIOLOGY, 2004, 186 (16) :5432-5441
[7]   Prokaryotic chromosomes and disease [J].
Hacker, J ;
Hentschel, U ;
Dobrindt, U .
SCIENCE, 2003, 301 (5634) :790-793
[8]   Polyketide and non-ribosomal peptide synthases: Falling together by coming apart [J].
Hutchinson, CR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (06) :3010-3012
[9]   Phylogenetic distribution of virulence-associated genes among Escherichia coli isolates associated with neonatal bacterial meningitis in the Netherlands [J].
Johnson, JR ;
Oswald, E ;
O'Bryan, TT ;
Kuskowski, MA ;
Spanjaard, L .
JOURNAL OF INFECTIOUS DISEASES, 2002, 185 (06) :774-784
[10]   Pathogenic Escherichia coli [J].
Kaper, JB ;
Nataro, JP ;
Mobley, HLT .
NATURE REVIEWS MICROBIOLOGY, 2004, 2 (02) :123-140