Overexpression of genes of the cell wall stimulon in clinical isolates of Staphylococcus aureus exhibiting vancomycin-intermediate-S-aureus-type resistance to vancomycin
Overexpression of genes of the cell wall stimulon in clinical isolates of Staphylococcus aureus exhibiting vancomycin-intermediate-S-aureus-type resistance to vancomycin
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DOI：
10.1128/jb.188.3.1120-1133.2006
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发表时间：
2006-02-01
影响因子：
3.2
通讯作者：
Tomasz, A
中科院分区：
文献类型：
--
作者：
McAleese, F;Wu, SW;Tomasz, A
使用定制设计的基因芯片(Affymetrix)来确定万古霉素MIC增加的金黄色葡萄球菌分离株的遗传相关性和基因表达谱，这些金黄色葡萄球菌分离株是从一名接受广泛万古霉素治疗的患者的血液和心脏瓣膜中恢复的，持续了几周。通过基于基因芯片的基因分型方法，这些分离株被发现是等基因的，从而为研究可能导致万古霉素耐药表型的基因表达变化提供了独特的机会。从患者接触者鼻腔分离的亲本菌株JH1和JH15之间没有发现基因表达的差异。相同的万古霉素MIC的血液和心脏瓣膜分离株之间几乎没有观察到表达变化。与JH1(MIC=1 mU g/m l)相比，JH9(MIC=8 m u g/m l)后期有大量基因表达发生了变化。大多数表达改变的基因参与了管家功能或细胞壁的生物合成和调节。在JH9中，索酸酶编码基因srtA和srtB以及几个表面蛋白编码基因表达下调。两个假想的蛋白质编码基因SAS016和SA2343在JH9中显著过表达。有趣的是，在无药物培养的JH9中，当亲本菌株JH1短暂地暴露于万古霉素的抑制浓度时，发现27个表达改变的基因也过表达，并且超过一半(27个中的17个)表达改变的基因属于被认为构成一般细胞壁应激刺激的决定因素(S.Utaida等，Microbiology 149：2719-2732,2003)。
Custom-designed gene chips (Affymetrix) were used to determine genetic relatedness and gene expression profiles in Staphylococcus aureus isolates with increasing MICs of vancomycin that were recovered over a period of several weeks from the blood and heart valve of a patient undergoing extensive vancomycin therapy. The isolates were found to be isogenic as determined by the GeneChip based genotyping approach and thus represented a unique opportunity to study changes in gene expression that may contribute to the vancomycin resistance phenotype. No differences in gene expression were detected between the parent strain, JH1, and JH15, isolated from the nares of a patient contact. Few expression changes were observed between blood and heart valve isolates with identical vancomycin MICs. A large number of genes had altered expression in the late stage JH9 isolate (MIC = 8 mu g/ml) compared to JH1 (MIC = 1 mu g/ml). Most genes with altered expression were involved in housekeeping functions or cell wall biosynthesis and regulation. The sortase-encoding genes, srtA and srtB, as well as several surface protein-encoding genes were downregulated in JH9. Two hypothetical protein-encoding genes, SAS016 and SA2343, were dramatically overexpressed in JH9. Interestingly, 27 of the genes with altered expression in JH9 grown in drug-free medium were found to be also overexpressed when the parental strain JH1 was briefly exposed to inhibitory concentrations of vancomycin, and more than half (17 of 27) of the genes with altered expression belonged to determinants that were proposed to form part of a general cell wall stress stimulon (S. Utaida et al., Microbiology 149:2719-2732, 2003).