Identification of critical staphylococcal genes using conditional phenotypes generated by antisense RNA.
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.
Ji
Y
Y
Department of Microbiology, Genetics Research, GlaxoSmithKline Pharmaceuticals Research and Development, Collegeville, PA 19426, USA. yinduo_ji-1@gsk.com
Zhang
B
B
Van
S F
SF
Horn
Warren
P
P
Woodnutt
G
G
Burnham
M K
MK
Rosenberg
M
M
D000818:Animals; D003001:Cloning, Molecular; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D020043:Genes, Essential; D005822:Genetic Vectors; D051379:Mice; D016366:Open Reading Frames; D010641:Phenotype; D011704:Pyelonephritis / Q000382:microbiology; D016372:RNA, Antisense; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D014169:Transformation, Bacterial; D014774:Virulence / Q000235:genetics
D016372:RNA, Antisense