Identification of critical staphylococcal genes using conditional phenotypes generated by antisense RNA

被引：328

作者：

Ji, YD

Zhang, B

Van Horn, SF

Warren, P

Woodnutt, G

Burnham, MKR

Rosenberg, M

机构：

[1] GlaxoSmithKline Pharmaceut Res & Dev, Dept Microbiol, Collegeville, PA 19426 USA

[2] GlaxoSmithKline Pharmaceut Res & Dev, Genet Res, Collegeville, PA 19426 USA

来源：

SCIENCE | 2001年 / 293卷 / 5538期

关键词：

D O I：

10.1126/science.1063566

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：

Comprehensive genomic analysis of the important human pathogen Staphylococcus aureus was achieved by a strategy involving antisense technology in a regulatable gene expression system. In addition to known essential genes, many genes of unknown or poorly defined biological function were identified. This methodology allowed gene function to be characterized in a comprehensive, defined set of conditionally growth-defective/lethal isogenic strains. Quantitative titration of the conditional growth effect was performed either in bacterial culture or in an animal model of infection. This genomic strategy offers an approach to the identification of staphylococcal gene products that could serve as targets for antibiotic discovery.

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收藏

页码：2266 / 2269

页数：4

相关论文

共 24 条

[1] Mixed-backbone oligonucleotides as second generation antisense oligonucleotides: In vitro and in vivo studies [J].

Agrawal, S ;

Jiang, ZW ;

Zhao, QY ;

Shaw, D ;

Cai, QY ;

Roskey, A ;

Channavajjala, L ;

Saxinger, C ;

Zhang, RW .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (06) :2620-2625

[2] Systematic identification of essential genes by in vitro mariner mutagenesis [J].

Akerley, BJ ;

Rubin, EJ ;

Camilli, A ;

Lampe, DJ ;

Robertson, HM ;

Mekalanos, JJ .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (15) :8927-8932

[3] Gapped BLAST and PSI-BLAST: a new generation of protein database search programs [J].

Altschul, SF ;

Madden, TL ;

Schaffer, AA ;

Zhang, JH ;

Zhang, Z ;

Miller, W ;

Lipman, DJ .

NUCLEIC ACIDS RESEARCH, 1997, 25 (17) :3389-3402

[4] A genome-based approach for the identification of essential bacterial genes [J].

Arigoni, F ;

Talabot, F ;

Peitsch, M ;

Edgerton, MD ;

Meldrum, E ;

Allet, E ;

Fish, R ;

Jamotte, T ;

Curchod, ML ;

Loferer, H .

NATURE BIOTECHNOLOGY, 1998, 16 (09) :851-856

[5] Antisense RNA-mediated transcriptional attenuation:: an in vitro study of plasmid pT181 [J].

Brantl, S ;

Wagner, EGH .

MOLECULAR MICROBIOLOGY, 2000, 35 (06) :1469-1482

[6] INSERTIONAL INACTIVATION OF A CHROMOSOMAL LOCUS THAT MODULATES EXPRESSION OF POTENTIAL VIRULENCE DETERMINANTS IN STAPHYLOCOCCUS-AUREUS [J].

CHEUNG, AL ;

WOLZ, C ;

YEAMAN, MR ;

BAYER, AS .

JOURNAL OF BACTERIOLOGY, 1995, 177 (11) :3220-3226

[7] An antisense-based functional genomics approach for identification of genes critical for growth of Candida albicans [J].

De Backer, MD ;

Nelissen, B ;

Logghe, M ;

Viaene, J ;

Loonen, I ;

Vandoninck, S ;

de Hoogt, R ;

Dewaele, S ;

Simons, FA ;

Verhasselt, P ;

Vanhoof, G ;

Contreras, R ;

Luyten, WHML .

NATURE BIOTECHNOLOGY, 2001, 19 (03) :235-241

[8] SUPPRESSION OF VILLIN EXPRESSION BY ANTISENSE RNA IMPAIRS BRUSH-BORDER ASSEMBLY IN POLARIZED EPITHELIAL INTESTINAL-CELLS [J].

DEBEAUREGARD, MAC ;

PRINGAULT, E ;

ROBINE, S ;

LOUVARD, D .

EMBO JOURNAL, 1995, 14 (03) :409-421

[9] ANALYSIS OF PSEUDOMONAS GENE-PRODUCTS USING LACIQ PTRP-LAC PLASMIDS AND TRANSPOSONS THAT CONFER CONDITIONAL PHENOTYPES [J].

DELORENZO, V ;

ELTIS, L ;

KESSLER, B ;

TIMMIS, KN .

GENE, 1993, 123 (01) :17-24

[10] Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans [J].

Fire, A ;

Xu, SQ ;

Montgomery, MK ;

Kostas, SA ;

Driver, SE ;

Mello, CC .

NATURE, 1998, 391 (6669) :806-811