Transcriptional modulation of some Staphylococcus aureus iron-regulated genes during growth in vitro and in a tissue cage model in vivo

• Published in: Microbes and infection 2006-06, Vol.8 (7), p.1679-1690
• Main Authors: Allard, Marianne, Moisan, Hélène, Brouillette, Éric, Gervais, Alain L., Jacques, Mario, Lacasse, Pierre, Diarra, Moussa S., Malouin, François
• Format: Article
• Language: English
• Subjects: Adaptation, Physiological; Animals; Bacterial Proteins - genetics; Bacteriology; Binding Sites - genetics; Biological and medical sciences; Diffusion Chambers, Culture; DNA array; Female; Fundamental and applied biological sciences. Psychology; Gene Expression Profiling; Gene Expression Regulation, Bacterial; Genes, Bacterial; Iron; Iron - metabolism; Mice; Microbiology; Miscellaneous; Oligonucleotide Array Sequence Analysis; Repressor Proteins - genetics; Reverse Transcriptase Polymerase Chain Reaction; RNA, Bacterial - analysis; RNA, Bacterial - genetics; RNA, Bacterial - isolation & purification; Small RNA; Staphylococcus aureus; Staphylococcus aureus - genetics; Staphylococcus aureus - metabolism; Transcription, Genetic; Up-Regulation
• ISSN: 1286-4579; 1769-714X
• DOI: 10.1016/j.micinf.2006.01.022

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.