changes in the staphylococcus aureus transcriptome during early adaptation to the lung金黄色葡萄球菌转录组的变化在早期适应肺.pdfVIP

Changes in the Staphylococcus aureus Transcriptome during Early Adaptation to the Lung 1 2 2 1,2 Donald O. Chaffin , Destry Taylor , Shawn J. Skerrett , Craig E. Rubens * 1 Seattle Children’s Hospital Research Institute, Seattle, Washington, United States of America, 2 University of Washington, Seattle, Washington, United States of America Abstract Staphylococcus aureus is a common inhabitant of the human nasopharynx. It is also a cause of life-threatening illness, producing a potent array of virulence factors that enable survival in normally sterile sites. The transformation of S. aureus from commensal to pathogen is poorly understood. We analyzed S. aureus gene expression during adaptation to the lung using a mouse model of S. aureus pneumonia. Bacteria were isolated by bronchoalveolar lavage after residence in vivo for up to 6 hours. S. aureus in vivo RNA transcription was compared by microarray to that of shake flask grown stationary phase and early exponential phase cells. Compared to in vitro conditions, the in vivo transcriptome was dramatically altered within 30 minutes. Expression of central metabolic pathways changed significantly in response to the lung environment. Gluconeogenesis (fbs, pckA) was down regulated, as was TCA cycle and fermentation pathway gene expression. Genes associated with amino acid synthesis, RNA translation and nitrate respiration were upregulated, indicative of a highly active metabolic state during the first 6 hours in the lung. Virulence factors regulated by agr were down regulated in vivo and in early exponential phase compared to stationary phase cells. Over time in vivo, expression of ahpCF, involved in H2O2