title: Microarray analysis of pneumococcal gene expression during invasive disease.
abstract: Streptococcus pneumoniae is a leading cause of invasive bacterial disease. This is the first study to examine the expression of S. pneumoniae genes in vivo by using whole-genome microarrays available from The Institute for Genomic Research. Total RNA was collected from pneumococci isolated from infected blood, infected cerebrospinal fluid, and bacteria attached to a pharyngeal epithelial cell line in vitro. Microarray analysis of pneumococcal genes expressed in these models identified body site-specific patterns of expression for virulence factors, transporters, transcription factors, translation-associated proteins, metabolism, and genes with unknown function. Contributions to virulence predicted for several unknown genes with enhanced expression in vivo were confirmed by insertion duplication mutagenesis and challenge of mice with the mutants. Finally, we cross-referenced our results with previous studies that used signature-tagged mutagenesis and differential fluorescence induction to identify genes that are potentially required by a broad range of pneumococcal strains for invasive disease.
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Orihuela
authors.forename: Jana N
authors.initials: JN
authors.lastname: Radin
authors.forename: Jack E
authors.initials: JE
authors.lastname: Sublett
authors.forename: Geli
authors.initials: G
authors.lastname: Gao
authors.forename: Deepak
authors.initials: D
authors.lastname: Kaushal
authors.forename: Elaine I
authors.initials: EI
authors.lastname: Tuomanen
mesh_terms: D000818:Animals; D002460:Cell Line; D004847:Epithelial Cells / Q000382:microbiology; D005260:Female; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial / Q000235:genetics*; D016680:Genome, Bacterial; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D011008:Pneumococcal Infections / Q000097:blood / Q000134:cerebrospinal fluid / Q000821:virology*; D012329:RNA, Bacterial / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D013296:Streptococcus pneumoniae / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity / Q000502:physiology; D014774:Virulence / Q000235:genetics
chemical_list: D012329:RNA, Bacterial