Transcriptional modulation of some Staphylococcus aureus iron-regulated genes during growth in vitro and in a tissue cage model in vivo.
Staphylococcus aureus can proliferate in iron-limited environments such as the mammalian host. The transcriptional profiles of 460 genes (iron-regulated, putative Fur-regulated, membrane transport, pathogenesis) obtained for S. aureus grown in iron-restricted environments in vitro and in vivo were compared in order to identify new iron-regulated genes and to evaluate their potential as possible therapeutic targets in vivo. Iron deprivation was created in vitro by 2,2-dipyridyl, and in vivo, S. aureus was grown in tissue cages implanted in mice. Bacterial RNA was obtained from each growth condition and cDNA probes were co-hybridized on DNA arrays. Thirty-six upregulated and 11 downregulated genes were commonly modulated in animals and in the low-iron medium. Real-time PCR confirmed the iron-dependent modulation of four novel genes (SACOL0161, 2170, 2369, 2431) with a Fur box motif. Some genes expressed in the dipyridyl medium were not expressed in vivo (e.g., copA, frpA, SACOL1045). Downregulated genes included an iron-storage protein gene and genes of the succinate dehydrogenase complex, reminiscent of a small RNA-dependent regulation thus far only demonstrated in Gram-negative bacteria. The expression of iron-regulated genes in distinct low-iron environments provided insight into their relative importance in vitro and in vivo and their usefulness for vaccine and drug development.
Allard
Marianne
M
Centre d'Etude et de Valorisation de la Diversité Microbienne (CEVDM), Département de Biologie, Faculté des Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada.
Moisan
Hélène
H
Brouillette
Eric
E
Gervais
Alain L
AL
Jacques
Mario
M
Lacasse
Pierre
P
Diarra
Moussa S
MS
Malouin
François
F
D000222:Adaptation, Physiological; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D015194:Diffusion Chambers, Culture; D005260:Female; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D007501:Iron / Q000378:metabolism*; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D012329:RNA, Bacterial / Q000032:analysis / Q000235:genetics / Q000302:isolation & purification; D012097:Repressor Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013211:Staphylococcus aureus / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D015854:Up-Regulation
D001426:Bacterial Proteins; D012329:RNA, Bacterial; D012097:Repressor Proteins; C068477:ferric uptake regulating proteins, bacterial; D007501:Iron